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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02966834
Additional trial details provided through ANZCTR are available at the end of this record.
Registration number
NCT02966834
Ethics application status
Date submitted
15/11/2016
Date registered
17/11/2016
Date last updated
4/05/2021
Titles & IDs
Public title
Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis
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Scientific title
A Randomized, Double-blind, Multi-dose, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of GSK2330672 Administration for the Treatment of Pruritus in Patients With Primary Biliary Cholangitis (GLIMMER: GSK2330672 triaL of IBAT Inhibition With Multidose Measurement for Evaluation of Response)
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Secondary ID [1]
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2016-002416-41
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Secondary ID [2]
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201000
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cholestasis
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0
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Condition category
Condition code
Oral and Gastrointestinal
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0
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0
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Infection
0
0
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0
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Other infectious diseases
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Skin
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0
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0
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Other skin conditions
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - GSK2330672
Placebo Comparator: Placebo - Participants will receive matching placebo
Experimental: GSK2330672 20 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind
Experimental: GSK2330672 90 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind
Experimental: GSK2330672 180 mg once daily - Participants will receive GSK2330672 and matching placebo to maintain blind
Experimental: GSK2330672 40 mg twice daily - Participants will receive GSK2330672 and matching placebo to maintain blind
Experimental: GSK2330672 90 mg twice daily - Participants will receive GSK2330672 and matching placebo to maintain blind
Treatment: Drugs: Placebo
GSK2330672 matching placebo will be supplied as white film-coated tablets.
Treatment: Drugs: GSK2330672
GSK2330672 will be supplied in 2 dose strengths of 10 mg and 45 mg white film-coated tablets.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score
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Assessment method [1]
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Participants were required to score the severity of their itching using a 0-10 numerical rating scale (NRS) where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the average of the scores in the 7 days prior to the Week 4 (Visit 3 [V3]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was done using Analysis of covariance (ANCOVA) including treatment group and centered Mean Worst Daily Itch score at Baseline.
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Timepoint [1]
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Baseline and Week 16
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Secondary outcome [1]
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Mean Change From Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) Scale
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Assessment method [1]
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PBC-40 is a disease-specific health-related quality of life (HRQoL) questionnaire for use in PBC participants. It consists of 40 questions arranged in 6 domains with 3 to 11 questions in each domain. Each question is scored from 1 (least impact) to 5 (greatest impact). All questions within a domain are summed to obtain individual domain score. Domains were: Symptoms (7 questions) with score range 7-35, Itch (3 questions) with score range 3-15, Fatigue (11 questions) with score range 11-55, Cognitive (6 questions) with score range 6-30, Emotional (3 questions) with score range 3-15, and Social (10 questions) with score range 10-50. Higher scores for individual domains represent a poor quality of life. Baseline is the assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
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Timepoint [1]
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Baseline and at Week 16
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Secondary outcome [2]
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Mean Change From Baseline at Week 16 in Serum Alkaline Phosphatase (ALP) Concentrations, in Participants With High Risk of PBC Progression
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Assessment method [2]
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Criteria for high risk of PBC progression is defined as serum ALP concentrations more than or equal to (>=)1.67 times upper limit of normal (ULN) range and/or total bilirubin concentrations more than (>)ULN at Day 1. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
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Timepoint [2]
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Baseline and at Week 16
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Secondary outcome [3]
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Number of Participants With Serum ALP Concentrations Less Than (<)1.67 Times ULN and Total Bilirubin Concentrations Less Than or Equal to (<=) ULN at Week 16
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Assessment method [3]
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Number of participants with ALP < 1.67 times ULN and total bilirubin <= ULN at Week 16 is presented. The endpoint was analyzed in Restricted High Risk Population.
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Timepoint [3]
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At Week 16
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Secondary outcome [4]
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Mean Change From Baseline at Week 16 in Serum Alanine Aminotransferase (ALT) Among Those With a High Risk of PBC Progression
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Assessment method [4]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline.
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Timepoint [4]
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Baseline and at Week 16
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Secondary outcome [5]
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Mean Change From Baseline at Week 16 in Serum Aspartate Aminotransferase (AST) Among Those With a High Risk of PBC Progression
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Assessment method [5]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline.
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Timepoint [5]
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Baseline and at Week 16
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Secondary outcome [6]
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Mean Change From Baseline at Week 16 in Serum Gamma Glutamyl Transferase (GGT), Among Those With a High Risk of PBC Progression
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Assessment method [6]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
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Timepoint [6]
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Baseline and at Week 16
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Secondary outcome [7]
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Mean Change From Baseline at Week 16 in Total Bilirubin Concentration, Among Those With a High Risk of PBC Progression
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Assessment method [7]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
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Timepoint [7]
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Baseline and at Week 16
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Secondary outcome [8]
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Mean Change From Baseline at Week 16 in Albumin Concentration, Among Those With a High Risk of PBC Progression
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Assessment method [8]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
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Timepoint [8]
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Baseline and at Week 16
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Secondary outcome [9]
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Mean Change From Baseline at Week 16 in Prothrombin International Normalized Ratio (INR), Among Those With a High Risk of PBC Progression
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Assessment method [9]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
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Timepoint [9]
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Baseline and at Week 16
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Secondary outcome [10]
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Mean Change From Baseline at Week 16 in Prothrombin Time, Among Those With a High Risk of PBC Progression
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Assessment method [10]
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Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
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Timepoint [10]
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Baseline and at Week 16
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Secondary outcome [11]
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Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) -Main Study Period
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Assessment method [11]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
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Timepoint [11]
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Up to 12 weeks
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Secondary outcome [12]
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Number of Participants With Non-SAEs and SAEs -Final Study Period
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Assessment method [12]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
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Timepoint [12]
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Up to 4 weeks
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Secondary outcome [13]
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Number of Participants With Non-SAEs and SAEs - Follow-up Period
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Assessment method [13]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
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Timepoint [13]
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Up to 4 weeks
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Secondary outcome [14]
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Number of Participants With Clinical Chemistry Data of Potential Clinical Importance
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Assessment method [14]
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Blood samples were collected to measure analyze the following parameters: albumin, calcium, Glomerular filtration rate (GFR) from creatinine, glucose, potassium and sodium. Participants were counted in the worst case category that their value changes to (low, within range [w/in] or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100 percent (%). Only "To Low" and/or "To High" categories with potential clinical importance data have been presented.
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Timepoint [14]
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At Weeks 8, 12, 16 and 20
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Secondary outcome [15]
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Number of Participants With Hematology Data of Potential Clinical Importance
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Assessment method [15]
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Blood samples were collected to analyze the following parameters: hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Participants were counted in the worst case category that their value changes to (low, w/in or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%. Only "To Low" and/or "To High" categories with potential clinical importance data have been presented.
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Timepoint [15]
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At Weeks 8, 12, 16 and 20
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Secondary outcome [16]
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Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Parameters
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Assessment method [16]
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A 12-lead ECG was recorded with the participant in a semi-supine position. 12-lead ECGs were obtained by using an automated ECG machine. Data for abnormal, not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
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Timepoint [16]
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At Weeks 8, 12, 16 and 20
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Secondary outcome [17]
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Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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Assessment method [17]
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SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Timepoint [17]
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Baseline and Week 20
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Secondary outcome [18]
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Change From Baseline in Pulse Rate
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Assessment method [18]
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Pulse rate was measured in a semi-supine position after 5 minutes of rest. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Timepoint [18]
0
0
Baseline and Week 20
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Secondary outcome [19]
0
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Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Assessment
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Assessment method [19]
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GSRS is a validated scale used to assess gastrointestinal symptoms experienced by participants over the preceding 5 to 7 days. GSRS was measured for all 5 domains: Average Diarrhea Syndrome Score, Average Indigestion Syndrome Score, Average Constipation Syndrome Score, Average Abdominal Pain Syndrome Score, Average Reflux Syndrome Score. All individual domains are scored on a 7-point Likert scale ranging from 1(not at all) to 7(extremely). Higher score indicate more severe symptoms. The Average Total GSRS score was mean of these 5 domains and ranges from 1 to 7. Higher score indicates worst possible degree of symptoms. The responses summarized at each visit are those given during the week prior to the visit, with exception of Day 1. Baseline is the most recent assessment completed by participant prior to randomization. Change from Baseline was calculated as post-Baseline value minus the Baseline value. Data has been presented for each domain along with the average Total GSRS score.
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Timepoint [19]
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Baseline and Week 20
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Secondary outcome [20]
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Number of Participants With Mean Worst Daily Itch Score of <4 at Week 16
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Assessment method [20]
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Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 is presented.
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Timepoint [20]
0
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At Week 16
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Secondary outcome [21]
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Number of Participants With Improvement of >= 30 Percent (%) in the Mean Worst Daily Itch Score at Week 16 From Baseline
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Assessment method [21]
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Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
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Timepoint [21]
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Baseline and At Week 16
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Secondary outcome [22]
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Number of Participants With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
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Assessment method [22]
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Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
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Timepoint [22]
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Baseline and At Week 16
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Secondary outcome [23]
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Percentage of Responder Days With Worst Daily Itch Score of <4
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Assessment method [23]
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Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Percentage of responder days with Worst Daily Itch Score of <4 is presented.
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Timepoint [23]
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0
Up to Week 16
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Secondary outcome [24]
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0
Percentage of Responder Days With Improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 From Baseline
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Assessment method [24]
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Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented..
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Timepoint [24]
0
0
Baseline and at Week 16
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Secondary outcome [25]
0
0
Percentage of Responder Days With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline
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Assessment method [25]
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Percentage of Responder Days with Worst Daily Itch was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
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Timepoint [25]
0
0
Baseline and at Week 16
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Secondary outcome [26]
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Change From Baseline in the Mean Daily Sleep Score at Week 16
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Assessment method [26]
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Mean Daily Sleep Score is defined as the average of the daily sleep scores provided in the 7 days prior to the relevant visit. Participants sleep quality was recorded in an electronic diary each morning using a 0-10 NRS in which 0: good sleep to 10:worst possible sleep. Higher score indicates worse possible sleep. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline.
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Timepoint [26]
0
0
Baseline and at Week 16
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Secondary outcome [27]
0
0
Change From Baseline in the Mean Daily Fatigue Score at Week 16
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Assessment method [27]
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Mean Daily Fatigue Score is defined as the average of the daily fatigue scores provided in the 7 days prior to the relevant visit. Participants fatigue level was recorded in an electronic diary each evening using a 0-10 NRS in which 0: no fatigue to 10:worst possible fatigue. Higher score indicates worse possible fatigue. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline.
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Timepoint [27]
0
0
Baseline and at Week 16
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Secondary outcome [28]
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0
Change From Baseline in the Five-Dimensional (5-D) Itch Scale at Week 16
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Assessment method [28]
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The 5-D itch scale had been developed as a brief, single page, instrument for the multidimensional quantification of itch that is sensitive to change over time. It has data to support its validity in a population of participants with pruritus and covers five dimensions of itch experienced by participants: duration, degree, direction, disability and distribution. Each domain was scored on a 5-point scale, ranging from 1 (Not present/resolved/never) to 5 (unbearable/getting worse/always), higher scores indicates worst itching. The scores of each of five domains were achieved separately and then summed together to obtain a total 5-D score. A total 5-D scores potentially ranged between 5 (no pruritus) and 25 (most severe pruritus) where higher score indicates worse possible itching. Baseline is assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value.
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Timepoint [28]
0
0
Baseline and at Week 16
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Secondary outcome [29]
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0
Mean Change From Baseline at Week 16 in Serum Total Bile Acid Concentration
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Assessment method [29]
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Blood samples were collected for evaluating total bile acid concentration as a biomarker of PBC. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Timepoint [29]
0
0
Baseline and at Week 16
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Secondary outcome [30]
0
0
Mean Change From Baseline at Week 16 in Serum 7-alpha Hydroxy-4-cholesten-3-one (C4)
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Assessment method [30]
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0
Blood samples were collected for evaluating C4 concentration as a marker of bile acid synthesis. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Timepoint [30]
0
0
Baseline and at Week 16
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Secondary outcome [31]
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0
Plasma Concentration of GSK2330672 After Sparse Sampling
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Assessment method [31]
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Blood samples were collected for measurement of plasma GSK2330672 concentration.
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Timepoint [31]
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0
At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)
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Eligibility
Key inclusion criteria
Inclusion Criteria
- Participant must be 18 to 80 years of age inclusive, at the time of signing the
informed consent.
- Participants who have proven PBC, as demonstrated by having at least 2 of the
following: History of sustained increased ALP levels >ULN first recognized at least 6
months prior to the Screening Visit (Sustained ALP elevations at the time of Screening
is not required, recognizing that the ALP may have decreased after institution of
ursodeoxycholic acid (UDCA) therapy as described in inclusion number 4). Documented
positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or
M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear
antibodies (antinuclear dot and/or nuclear rim positive). Liver biopsy (at any time in
the past) consistent with PBC.
- Participants must rate their itch severity as being >=4 on a 0 to 10 point scale for
the majority of time (at least half the days, as recalled by the participant) during
the 8 weeks prior to the Screening Visit. Periods of low itch or no itch are
acceptable as long as the worst daily itch score is >=4 on the majority of days.
- Participants who are currently taking UDCA should be on stable doses of UDCA for >8
weeks at time of screening. Participants not taking UDCA due to intolerance may be
enrolled 8 weeks after their last dose of UDCA. No changes or discontinuation is
permitted until completion of the Main Study Period.
- Male and/or female: Female participants- A female participant is eligible to
participate if she is not pregnant, not breastfeeding, and at least one of the
following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP
who agrees to follow the contraceptive guidance during the treatment period and until
at least 4 weeks after the last dose of study treatment.
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.
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Minimum age
18
Years
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Maximum age
80
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria
- Screening total bilirubin >2x ULN. Total bilirubin >2x ULN is acceptable if bilirubin
is fractionated and direct bilirubin <35 percent (%).
- Screening ALT or AST >6x ULN.
- Screening eGFR <45 milliliter (mL)/minute/1.73 square meter (m^2) based on the
CKD-EPI.
- History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy
or ascites).
- Presence of actively replicating viral hepatitis due to hepatitis B or C virus (HBV,
HCV) infection, and/or confirmed hepatocellular carcinoma or biliary cancer. Other
hepatic conditions ( e.g., primary sclerosing cholangitis [PSC], alcoholic liver
disease, autoimmune hepatitis, non-alcoholic steatohepatitis [NASH] ) are permitted if
PBC is the dominant liver injury in the investigator's opinion.
- Current diarrhea.
- Current symptomatic cholelithiasis or inflammatory gall bladder disease. Participants
with history of cholecystectomy >=3 months before screening may be eligible for
enrolment.
- Any current medical condition (e.g. psychiatric disorder, senility or dementia), which
may affect the participant's ability to comply with the protocol specified procedures.
- Initiation or increase in dose of colchicine, methotrexate, azathioprine, or systemic
corticosteroids in the 2 months prior to screening. If a change in dose in any of
these medications is anticipated during the course of the study, the participant
should be excluded.
- Initiation or increase in dose of bezafibrate or fenofibrate at any time during the 3
months prior to screening. Participants may join the study on stable doses of these
medications, but no change or discontinuation is permitted until completion of the
Main Study Period.
- Initiation or increase in dose of any of the following in the 8 weeks prior to
screening: rifampicin, naltrexone, naloxone, nalfurafine, or sertraline. Participants
may join the study on stable or decreased doses of these medications, but no change in
dose is permitted until completion of the Main Study Period.
- Bile acid binding resin use: a participant must discontinue use of cholestyramine,
colesevelam, colestipol or colestimide prior to the start of the Initial Study Period
(no later than Day-2). Note: these drugs may be administered after completion of the
Main Study Period, if clinically indicated.
- Obeticholic acid use: a participant must discontinue use of obeticholic acid at least
8 weeks prior to the start of the Initial Study Period and may not restart until after
the end of the study.
- Administration of any other Inhibitor of the Human Ileal Bile Acid Transporter (IBAT)
in the 3 months prior to screening.
- Current enrolment or participation within the 8 weeks before start of the Initial
Study Period, in any other clinical study involving an investigational study
treatment.
- QT interval corrected for heart rate QTc >480 millisecond (msec).
- History of sensitivity to the study treatment or components thereof or a history of
drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline
(GSK) Medical Monitor, contraindicates their participation in the study.
- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass
(125 mL) of wine or 1 measure (25 mL) of spirits.
Query!
Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
11/01/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
15/04/2020
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Sample size
Target
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Accrual to date
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Final
147
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
0
0
GSK Investigational Site - Camperdown
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Recruitment hospital [2]
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0
GSK Investigational Site - Herston
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Recruitment hospital [3]
0
0
GSK Investigational Site - Prahran
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Recruitment hospital [4]
0
0
GSK Investigational Site - Nedlands
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Recruitment postcode(s) [1]
0
0
2050 - Camperdown
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Recruitment postcode(s) [2]
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4029 - Herston
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Recruitment postcode(s) [3]
0
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3181 - Prahran
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Recruitment postcode(s) [4]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Arizona
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Country [2]
0
0
United States of America
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State/province [2]
0
0
California
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Country [3]
0
0
United States of America
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State/province [3]
0
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Florida
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Michigan
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Country [5]
0
0
United States of America
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State/province [5]
0
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New Jersey
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0
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United States of America
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State/province [6]
0
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New York
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0
0
United States of America
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State/province [7]
0
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Pennsylvania
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0
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United States of America
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State/province [8]
0
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Texas
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0
0
United States of America
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State/province [9]
0
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Washington
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0
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Canada
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State/province [10]
0
0
Alberta
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Country [11]
0
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Canada
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State/province [11]
0
0
Manitoba
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Country [12]
0
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Canada
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State/province [12]
0
0
Ontario
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Country [13]
0
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Canada
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State/province [13]
0
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Quebec
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Country [14]
0
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France
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State/province [14]
0
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Clermont-Ferrand
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Country [15]
0
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France
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State/province [15]
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Grenoble Cedex 9
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Country [16]
0
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France
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State/province [16]
0
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Lille cedex
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Country [17]
0
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France
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State/province [17]
0
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Paris cedex 12
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Country [18]
0
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France
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State/province [18]
0
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Pessac cedex
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Country [19]
0
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Germany
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State/province [19]
0
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Bayern
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Country [20]
0
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Germany
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State/province [20]
0
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Saarland
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Country [21]
0
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Germany
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State/province [21]
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Hamburg
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Country [22]
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Italy
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State/province [22]
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Emilia-Romagna
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Country [23]
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Italy
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State/province [23]
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Lombardia
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Country [24]
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Italy
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State/province [24]
0
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Toscana
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Italy
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State/province [25]
0
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Veneto
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Country [26]
0
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Japan
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State/province [26]
0
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Chiba
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Country [27]
0
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Japan
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State/province [27]
0
0
Fukui
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Country [28]
0
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Japan
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State/province [28]
0
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Gunma
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Country [29]
0
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Japan
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State/province [29]
0
0
Hiroshima
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0
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Japan
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State/province [30]
0
0
Hokkaido
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0
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Japan
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State/province [31]
0
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Kagawa
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0
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Japan
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State/province [32]
0
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Kanagawa
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Country [33]
0
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Japan
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State/province [33]
0
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Nagasaki
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Country [34]
0
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Japan
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State/province [34]
0
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Osaka
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Japan
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State/province [35]
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Tokyo
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Country [36]
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Poland
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State/province [36]
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Czestochowa
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Country [37]
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Poland
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State/province [37]
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Katowice
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Poland
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State/province [38]
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Myslowice
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Country [39]
0
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Poland
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State/province [39]
0
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Warszawa
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Country [40]
0
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Poland
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State/province [40]
0
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Wroclaw
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Country [41]
0
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Spain
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State/province [41]
0
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Barcelona
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Country [42]
0
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Spain
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State/province [42]
0
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Madrid
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Country [43]
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Spain
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State/province [43]
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Sevilla
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Country [44]
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Spain
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State/province [44]
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Valencia
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Country [45]
0
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United Kingdom
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State/province [45]
0
0
Basingstoke
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Country [46]
0
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United Kingdom
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State/province [46]
0
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Edgbaston
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0
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United Kingdom
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State/province [47]
0
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Glasgow
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Country [48]
0
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United Kingdom
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State/province [48]
0
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Liverpool.
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Country [49]
0
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United Kingdom
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State/province [49]
0
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London
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Country [50]
0
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United Kingdom
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State/province [50]
0
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Manchester
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Country [51]
0
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United Kingdom
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State/province [51]
0
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Middlesbrough
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Country [52]
0
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United Kingdom
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State/province [52]
0
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Newcastle-upon-Tyne
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Country [53]
0
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United Kingdom
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State/province [53]
0
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Nottingham
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0
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United Kingdom
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State/province [54]
0
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Plymouth
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Country [55]
0
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United Kingdom
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State/province [55]
0
0
Sheffield
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This study is being conducted to evaluate the efficacy, safety and tolerability of GSK2330672
administration for the treatment of pruritus (itch) in participants with primary biliary
cholangitis (PBC). Participants will receive either placebo or one of the 4 dose regimens of
GSK2330672 (20 milligram [mg], 90 mg or 180 mg taken once daily or 90 mg twice daily).
Participants on GSK2330672 will also receive placebo tablets to maintain blinding. The study
has a prospectively defined adaptive design that will utilize interim data to further inform
and potentially optimize the doses under investigation. Hence, additional dose regimen may be
added during study. The total duration of a participant in the study will be up to 45 days of
screening and 24 weeks of study including follow-up.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02966834
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
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Address
0
0
GlaxoSmithKline
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02966834
Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,WA
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
Public notes
Investigators:
Richard Skoien, Royal Brisbane and Women's Hospital, Queensland, Herston, Australia, 4029
Simone Strasser, Royal Prince Alfred Hospital, New South Wales, Camperdown, Australia, 2050
George Garas, Sir Charles Gairdner Hospital, Western Australia, Nedlands, Australia, 6009
Contacts
Principal investigator
Title
69
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Name
69
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Address
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Phone
69
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Fax
69
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Email
69
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Contact person for public queries
Title
70
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Name
70
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Address
70
0
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Country
70
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Phone
70
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Fax
70
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Email
70
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[email protected]
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Contact person for scientific queries
Title
71
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Name
71
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Address
71
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71
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Phone
71
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Fax
71
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Email
71
0
[email protected]
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