The effect of repeat doses of GSK962040 on the pharmacokinetics of L-DOPA in subjects with Parkinson’s disease with slow gastric emptying

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2011-004438-32-GB
• Date of registration: 18/04/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: The effect of repeat doses of GSK962040 on the pharmacokinetics of L-DOPA in subjects with Parkinson’s disease with slow 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 levodopa in subjects with Parkinson’s disease exhibiting delayed gastric emptying - GSK962040 Parkinson's disease PoC
• Date of first enrolment: 25/04/2012
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004438-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Sweden, United Kingdom

Contacts

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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)
2. Subjects receiving a stable regimen of L-DOPA for at least four weeks prior to screening
3. Patient has gastroparesis at screening.
• A patient is eligible for Cohort 1 if the gastric half-time of emptying > 120.0 min as determined by 13C-oral breath test
• A patient is eligible for Cohort 2 if the gastric half-time of emptying > ULN and = 120.0 min as determined by 13C-oral breath test
4. Between 40 and 80 years of age, inclusive.
5. Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months
6. Dosage of any concomitant medications has been stable for at least 4 weeks
7. A female subject is eligible to participate if she is of:
o 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].
o 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.
8. ALT < 2xULN; alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
9. Single or Average QTc, QTcB or QTcF< 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Late stage advanced subjects with incapacitating peak dose or biphasic dyskinesia on a stable L-DOPA regime.
2. 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.
3. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
4. Patient has a gastric pacemaker
5. Patient is on chronic enteral (e.g., feeding tube) or parenteral feeding
6. Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months)
7. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
8. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
9. Lactating females.10. 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.
11. 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)
12. Unable to refrain from use of prohibited medications listed in Section 9 within the restricted timeframe relative to the first dose of study medication.
13. 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).
14. 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.
15. 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Investigate the ability of the motilin receptor agonist GSK962040 to improve levodopa pharmacokinetics (PK) by enhancing GE via motilin receptor agonism.
MedDRA version: 20.1 Level: PT Classification code 10051153 Term: Diabetic gastroparesis System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: GSK962040
Product Code: GSK962040
Pharmaceutical Form: Tablet
INN or Proposed INN: GSK962040
CAS Number: 923565-21-3
Current Sponsor code: GSK962040
Other descriptive name: GSK962040
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: GSK962040
Product Code: GSK962040
Pharmaceutical Form: Tablet
INN or Proposed INN: GSK962040
CAS Number: 923565-21-3
Current Sponsor code: GSK962040
Other descriptive name: GSK962040
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: GSK962040
Product Code: GSK962040
Pharmaceutical Form: Tablet
INN or Proposed INN: GSK962040
CAS Number: 923565-21-3
Current Sponsor code: GSK962040
Other descriptive name: GSK962040
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To measure the proportion of subjects who normalize GE rate with co-administration of GSK962040
• To measure the impact of co-administration of GSK962040 on symptoms of Parkinson’s disease
• To evaluate the effect of GSK962040 co-administration on gastroparesis symptoms
• To evaluate the safety and PK profile of GSK962040 in patients with Parkinson’s disease

Main Objective: To measure the effect of co-administration of GSK962040 on levodopa pharmacokinetic exposure in subjects with Parkinson’s disease with delayed gastric emptying

Timepoint(s) of evaluation of this end point: Days 1 and 8

Primary end point(s): L-DOPA PK at screening, Days 1 and 8: dose-normalized AUC(0-4), dose-normalized Cmax, Tmax, t½, (ka)

Secondary Outcome(s)

Secondary end point(s): • GE at screening, Days 1 and 8, as measured by OBT
(GE t½, GEC, GE Tlag) and
• UPDRS motor score at screening (baseline), Days 1 and 8
• Change from baseline in amount of awake time (in hours) spent “on,” “on” with troublesome dyskinesias, and “off” at screening, Days 1 through 8
• Non- motor symptoms scale at screening (baseline), Days 1 and 8
• Vital signs, clinical laboratory data and adverse events
• GSK962040 PK on Days 1 and 8: AUC, Cmax, Tmax, t½
Exploratory Endpoints
• Gastroparesis symptoms by GCSI-DD at screening, Days 1 through 8

Timepoint(s) of evaluation of this end point: Days 1 and 8

Secondary ID(s)

MOT115816

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 27/12/2014
• Date Completed: 01/05/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-004438-32/results