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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01602549
• Date of registration: 17/05/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• 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
• Date of first enrolment: July 2012
• Target sample size: 58
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01602549
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Australia, Germany, Sweden, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

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.

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.



Age minimum: 40 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Gastroparesis

Intervention(s)

Drug: Placebo

Drug: GSK962040 (25 mg tablet)

Primary Outcome(s)

Dose-normalized L-DOPA Cmax at Day 1 and Day 8 [Time Frame: Day 1 and Day 8]

L-DOPA Terminal Phase Half-life (t1/2) at Baseline, Day 1, and Day 8 [Time Frame: Baseline, Day 1, and Day 8]

L-DOPA Time of Occurrence of Cmax (Tmax) at Baseline, Day 1,and Day 8 [Time Frame: Baseline, Day 1, and Day 8]

Dose-normalized L-DOPA Maximum Observed Concentration (Cmax) at Baseline [Time Frame: Baseline]

Dose-normalized Levodopa (L-DOPA) Area Under the Plasma Concentration-time Curve From Zero to 4 Hours AUC(0-4) at Baseline [Time Frame: Baseline]

Dose-normalized L-DOPA AUC(0-4) at Day 1 and Day 8 [Time Frame: Day 1 and Day 8]

Secondary Outcome(s)

Change From Baseline in Mean Corpuscle Volume (MCV) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

Change From Baseline in Albumin (ALB) and Total Protein (TP) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Absolute Neutrophil Count (ANC), and Platelet Count (PC) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

Change From Baseline in Red Blood Cell Count (RBC) and White Blood Cell Count (WBC) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

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 [Time Frame: Baseline, Day 4, and Day 8]

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [Time Frame: From the start of study medication until Follow-up (up to Day 25)]

Change From Baseline in Hematocrit at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Day 1 and Day 8 [Time Frame: Day 1 and Day 8]

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 [Time Frame: Baseline, Day 4, and Day 8]

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 8 [Time Frame: Baseline, Day 1, and Day 8]

GSK962040 Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) at Day 1 [Time Frame: Day 1]

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Scores at Baseline, Day 1, and Day 8 (Pre-levodopa Dose) [Time Frame: Baseline, Day 1, and Day 8 at pre-levodopa dose]

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 [Time Frame: 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)]

Total Daily L-DOPA Equivalent Dose at Baseline and on Days 1, 2, 3, 4, 5, 6, 7, 8, and 9 [Time Frame: Baseline and Days 1, 2, 3, 4, 5, 6, 7, 8, and 9]

Gastric Half Emptying Time (GE t1/2) at Baseline (BL), Day 1, and Day 8 [Time Frame: Baseline, Day 1, and Day 8]

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 [Time Frame: Day 1 and Day 8]

Change From Baseline in Reticulocytes (RET) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

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 [Time Frame: 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)]

GSK962040 Cmax at Day1 and Day 8 [Time Frame: Day 1 and Day 8]

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) [Time Frame: 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)]

Change From Baseline in Heart Rate at Day 1 and Day 8 [Time Frame: Baseline, Day 1, and Day 8]

Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at Day 4 and Day 8 [Time Frame: Baseline, Day 4, and Day 8]

GSK962040 Tmax at Day1 and Day 8 [Time Frame: Day 1 and Day 8]

Secondary ID(s)

115816

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/02/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01602549