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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01602549




Registration number
NCT01602549
Ethics application status
Date submitted
17/05/2012
Date registered
21/05/2012
Date last updated
6/02/2017

Titles & IDs
Public title
A Study to Assess the Effect of Repeat Doses of GSK962040 on the Pharmacokinetics of L-DOPA in Subjects With Parkinson's Disease Exhibiting Delayed Gastric Emptying
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging Study to Assess the Effect of Repeat Doses of GSK962040 on the Pharmacokinetics of L-DOPA in Subjects With Parkinson's Disease Exhibiting Delayed Gastric Emptying
Secondary ID [1] 0 0
115816
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
Neurological 0 0 0 0
Parkinson's disease

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

Experimental: Cohort - 1:2 ratio, placebo, 50 mg administered orally once daily for 7-9 days


Treatment: Drugs: GSK962040 (25 mg tablet)
25 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
Dose-normalized Levodopa (L-DOPA) Area Under the Plasma Concentration-time Curve From Zero to 4 Hours AUC(0-4) at Baseline
Timepoint [1] 0 0
Baseline
Primary outcome [2] 0 0
Dose-normalized L-DOPA AUC(0-4) at Day 1 and Day 8
Timepoint [2] 0 0
Day 1 and Day 8
Primary outcome [3] 0 0
Dose-normalized L-DOPA Maximum Observed Concentration (Cmax) at Baseline
Timepoint [3] 0 0
Baseline
Primary outcome [4] 0 0
Dose-normalized L-DOPA Cmax at Day 1 and Day 8
Timepoint [4] 0 0
Day 1 and Day 8
Primary outcome [5] 0 0
L-DOPA Time of Occurrence of Cmax (Tmax) at Baseline, Day 1,and Day 8
Timepoint [5] 0 0
Baseline, Day 1, and Day 8
Primary outcome [6] 0 0
L-DOPA Terminal Phase Half-life (t1/2) at Baseline, Day 1, and Day 8
Timepoint [6] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [1] 0 0
Gastric Half Emptying Time (GE t1/2) at Baseline (BL), Day 1, and Day 8
Timepoint [1] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [2] 0 0
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose)
Timepoint [2] 0 0
Baseline, Day 1, and Day 8 at pre-levodopa dose
Secondary outcome [3] 0 0
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Scores at Baseline, Day 1, and Day 8 (Pre-dose; 120, 180, and 240 Minutes Post-dose)
Timepoint [3] 0 0
Baseline, Day 1, and Day 8 at pre-dose and 120, 180, and 240 minutes (min) post-dose (PD); Follow-up visit (up to Day 25)
Secondary outcome [4] 0 0
Period Mean Amount of Hours Spent "ON," "ON" Without Dyskinesia, "ON" With Non-troublesome Dyskinesia, "ON" With Troublesome Dyskinesia, and "OFF" at Baseline and During the Treatment Period (Days 1-8), Week 1 of Follow-up, and Week 2 of Follow-up
Timepoint [4] 0 0
Baseline, Days 1-8, Week 1 of Follow-up (Days 6 and 7 of Follow-up; up to Day 16), and Week 2 of Follow-up (Days 13 and 14 of Follow-up; up to Day 23)
Secondary outcome [5] 0 0
Number of Times a Participant Could Alternatively Tap Two Counter Keys 30 Centimeters Apart in 1 Minute (Min) at Baseline, Day1, Day 8, and Follow-up
Timepoint [5] 0 0
Baseline, Day 1, and Day 8 at pre-dose and 0, 30, 60, 90, 120, 180, and 240 minutes post-dose; Follow-up visit (up to Day 25)
Secondary outcome [6] 0 0
Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9
Timepoint [6] 0 0
Baseline and Days 1, 2, 3, 4, 5, 6, 7, 8, and 9
Secondary outcome [7] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8
Timepoint [7] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [8] 0 0
Change From Baseline in Heart Rate at Day 1 and Day 8
Timepoint [8] 0 0
Baseline, Day 1, and Day 8
Secondary outcome [9] 0 0
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8
Timepoint [9] 0 0
Day 1 and Day 8
Secondary outcome [10] 0 0
Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8
Timepoint [10] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [11] 0 0
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) at Day 4 and Day 8
Timepoint [11] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [12] 0 0
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content (CO2)/Bicarbonate (BC), Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN), and Uric Acid (UA) at Day 4 and Day 8
Timepoint [12] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [13] 0 0
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8
Timepoint [13] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [14] 0 0
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8
Timepoint [14] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [15] 0 0
Change From Baseline in Hematocrit at Day 4 and Day 8
Timepoint [15] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [16] 0 0
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at Day 4 and Day 8
Timepoint [16] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [17] 0 0
Change From Baseline in Mean Corpuscle Volume (MCV) at Day 4 and Day 8
Timepoint [17] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [18] 0 0
Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8
Timepoint [18] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [19] 0 0
Change From Baseline in Reticulocytes (RET) at Day 4 and Day 8
Timepoint [19] 0 0
Baseline, Day 4, and Day 8
Secondary outcome [20] 0 0
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Timepoint [20] 0 0
From the start of study medication until Follow-up (up to Day 25)
Secondary outcome [21] 0 0
GSK962040 Area Under the Plasma Concentration-time Curve From Zero to 5.5 Hours (AUC[0-5.5] and Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC[0-inf]) at Days 1 and 8
Timepoint [21] 0 0
Day 1 and Day 8
Secondary outcome [22] 0 0
GSK962040 Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) at Day 1
Timepoint [22] 0 0
Day 1
Secondary outcome [23] 0 0
GSK962040 Cmax at Day1 and Day 8
Timepoint [23] 0 0
Day 1 and Day 8
Secondary outcome [24] 0 0
GSK962040 Tmax at Day1 and Day 8
Timepoint [24] 0 0
Day 1 and Day 8

Eligibility
Key inclusion criteria
* Diagnosis of idiopathic Parkinson's Disease (according to modified Hoehn & Yahr criteria Stages II-IV) and with suboptimal motor control on L-DOPA or L-DOPA combination therapy (i.e. wearing off, peak dose dyskinesias, delayed on or no-on effects)
* Subjects receiving a stable regimen of L-DOPA for at least four weeks prior to screening
* Patient has gastric half-time of emptying > or = 70 min as determined by 13C oral breath test
* Between 40 and 80 years of age, 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 4 weeks
* A female subject 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 and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Child-bearing potential and is abstinent or 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 subjects must agree to use contraception until at least 5 days post-last dose.
* ALT < 2xULN; alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
* Single or Average QTc, QTcB or QTcF< 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Late stage advanced subjects with incapacitating peak dose or biphasic dyskinesia ona stable L-DOPA regime.
* Presence, or history within the previous 3 months, of significant and/or uncontrolled psychiatric, neurological (other than Parkinson's disease), gastro-intestinal, hematological, endocrinologic, neurological (other than Parkinson's disease), cardiovascular disease, active malignancy (other than basal cell cancer) or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
* Patient has a gastric pacemaker
* Patient is on chronic enteral (e.g., feeding tube) or parenteral feeding
* Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months)
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
* Lactating females.
* Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until followup.
* 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)
* Unable to refrain from use of prohibited medications listed in Section 9 within the restricted timeframe relative to the first dose of study medication.
* 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.

Study design
Purpose of the study
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 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
Germany
State/province [1] 0 0
Baden-Wuerttemberg
Country [2] 0 0
Germany
State/province [2] 0 0
Nordrhein-Westfalen
Country [3] 0 0
Germany
State/province [3] 0 0
Thueringen
Country [4] 0 0
Germany
State/province [4] 0 0
Berlin
Country [5] 0 0
Sweden
State/province [5] 0 0
Uppsala
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Cambridge
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Newcastle Upon Tyne
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Norwich

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

No information has been provided regarding IPD availability


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.