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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01262898




Registration number
NCT01262898
Ethics application status
Date submitted
16/12/2010
Date registered
17/12/2010

Titles & IDs
Public title
Dose Response of 28 Days of Dosing of GSK962040 in Type I and II Diabetic Male and Female Subjects With Gastroparesis
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase II Study to Evaluate the Safety and Efficacy and Dose Response of 28 Days of Once-Daily Dosing of the Oral Motilin Receptor Agonist GSK962040, in Type I and II Diabetic Male and Female Subjects With Gastroparesis
Secondary ID [1] 0 0
2010-023186-21
Secondary ID [2] 0 0
114479
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastroparesis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK962040 (5 mg tablet)
Treatment: Drugs - GSK962040 (25 mg tablet)
Treatment: Drugs - GSK962040 (125 mg tablet)
Treatment: Drugs - Placebo

Experimental: GSK962040 (10 mg) - GSK962040 10 mg

Experimental: GSK962040 (50 mg) - GSK962040 50 mg

Experimental: GSK962040 (125 mg) - GSK962040 125 mg

Experimental: Placebo - Placebo


Treatment: Drugs: GSK962040 (5 mg tablet)
5 mg tablet

Treatment: Drugs: GSK962040 (25 mg tablet)
25 mg tablet

Treatment: Drugs: GSK962040 (125 mg tablet)
125 mg tablet

Treatment: Drugs: Placebo
matching placebo tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Gastric Half Emptying Time (GEt1/2)
Timepoint [1] 0 0
Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28
Secondary outcome [1] 0 0
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)
Timepoint [1] 0 0
Up to follow-up (5-10 days post last dose)
Secondary outcome [2] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position
Timepoint [2] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [3] 0 0
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position
Timepoint [3] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [4] 0 0
Change From Baseline in Electrocardiography Parameters (12-lead ECG)
Timepoint [4] 0 0
Baseline, Day 1 and Day 28
Secondary outcome [5] 0 0
Number of Participants Outside the Normal Range for SBP and DBP
Timepoint [5] 0 0
Screening2/Baseline (Day -30 to -1), Day 1 and 28
Secondary outcome [6] 0 0
Number of Participants Outside the Normal Range for Heart Rate
Timepoint [6] 0 0
Screening2/Baseline (Day -30 to -1), Day 1 and 28
Secondary outcome [7] 0 0
Number of Participants Outside the Normal Range for 12-lead ECG
Timepoint [7] 0 0
Baseline (Day 1 pre-dose), Day 1, Day 14 and Day 28
Secondary outcome [8] 0 0
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase
Timepoint [8] 0 0
Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Secondary outcome [9] 0 0
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid
Timepoint [9] 0 0
Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Secondary outcome [10] 0 0
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein
Timepoint [10] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [11] 0 0
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate
Timepoint [11] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [12] 0 0
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count
Timepoint [12] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [13] 0 0
Mean Change From Baseline in Hematology Parameters : Hematocrit
Timepoint [13] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [14] 0 0
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin
Timepoint [14] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [15] 0 0
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration
Timepoint [15] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [16] 0 0
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume
Timepoint [16] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [17] 0 0
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes
Timepoint [17] 0 0
Baseline (Day 1 pre-dose) and Day 28
Secondary outcome [18] 0 0
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points
Timepoint [18] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [19] 0 0
Maximum Observed Concentration (Cmax) at Specified Time Points
Timepoint [19] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [20] 0 0
Time of Occurrence of Cmax (Tmax) at Specified Time Points
Timepoint [20] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [21] 0 0
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points
Timepoint [21] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [22] 0 0
Apparent Clearance Following Oral Dosing (CL/F) at Specified Time Points
Timepoint [22] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [23] 0 0
Apparent Volume of Distribution (V/F) at Specified Time Points
Timepoint [23] 0 0
Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Secondary outcome [24] 0 0
Apparent Terminal Elimination Half-life (t1/2) at Specified Time Points
Timepoint [24] 0 0
The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.
Secondary outcome [25] 0 0
Time to First Bowel Movement After First Dose
Timepoint [25] 0 0
Up to Day 28
Secondary outcome [26] 0 0
Daily Bowel Movement Frequency
Timepoint [26] 0 0
Up to Week 4 (Day 28)
Secondary outcome [27] 0 0
Daily Average Stool Consistency
Timepoint [27] 0 0
Up to Week 4 (Day 28)
Secondary outcome [28] 0 0
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD)
Timepoint [28] 0 0
Up to 14 days post last dose (Day 28)
Secondary outcome [29] 0 0
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC)
Timepoint [29] 0 0
Baseline(Screening i.e., Day -30 to -1), Day 1 and 28

Eligibility
Key inclusion criteria
* Type I or II Diabetes Mellitus (HbA1C < 10%)
* Male or female between 18 and 80 years of age, inclusive.
* Patient has gastroparesis at screening (gastric half-time of emptying > upper limit of normal as determined by 13C-oral breath test)
* Patient must have a > or = 3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, postprandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating > or = mild (2) and < or = severe (4) post-prandial fullness assessed using the GCSI-DD during the screening period prior to randomization.
* A female patient is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL, or a value consistent with the local laboratory standard value, is confirmatory. OR Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female patients must agree to use contraception for at least 5 days following the last dose of study medication.
* Male patients must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days after the last dose of study medication.
* BMI >18 and < or = 35.0 kg/m2 (inclusive).
* Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months
* Dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments.
* Estimated (or measured) glomerular filtration rate > or = 30 mL/min.
* QTcB or QTcF < 450 msec or QTc < 480 msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* AST and ALT < 2xULN; alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patient has acute severe gastroenteritis
* Patient has a gastric pacemaker
* Patient is on chronic parenteral feeding
* Patient has pronounced dehydration
* Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control diabetes or complications of diabetes
* Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months)
* Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia)
* Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics)
* Regular opiate use
* Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication.
* History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study.
* The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day time-period.
* Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing.
* Lactating females.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Sweden
State/province [14] 0 0
Uppsala
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cambridge
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Dundee
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study is available via the Clinical Study Data Request site

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20852


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.