A Randomized, Double-blind, Ascending Dose Trial to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics, of Repeat Doses of Motilin Receptor Agonist GSK962040 in Male and Female Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- GSK962040
- Conditions
- Gastroparesis
- Sponsor
- GlaxoSmithKline
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Safety, tolerability, and PK of GSK962040 from all adverse event reporting, 12-lead ECGs, vital signs, observation, safety laboratory tests and GI symptom diary; (AUC, Cmax, Tmax, accumulation ratio (Ro), half life and time invariance ratio (Rs)).
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study will evaluate the safety, tolerability and exposure of repeat escalating oral doses of GSK962040.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. In any case, liver function tests must be strictly within the normal range at screening.
- •Male or female between 18 and 55 years of age, inclusive.
- •Non-smoker for at least 6 months based on smoking history.
- •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 is confirmatory.
- •Child-bearing potential and agrees to use one of the contraception methods listed in the protocol 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 for at least 4 days following the last dose of study medication.
- •Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication through at least 4 days after the last dose of study medication.
- •Body weight \> 50 kg and BMI within the range 18.5 - 29.9 kg/m2 (inclusive).
- •QTcB or QTcF \< 450 msec or QTc\<480msec in subjects with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
- •Normal physical examination (physical exam demonstrates no evidence of clinically active disease or physical or mental impairment). A subject with a clinical abnormality may be included only if the Principal Investigator or physician designee considers that the abnormality will not introduce additional risk factors and will not interfere with the study procedures. Consultation with the GSK medical monitor is required before such subjects may be included.
Exclusion Criteria
- Not provided
Arms & Interventions
Subjects receiving GSK962040 in cohort 1
Eligible subjects will receive repeat oral doses of GSK962040 given as 10 milligrams once daily tablet for 14 days.
Intervention: GSK962040
Subjects receiving GSK962040 in cohort 1
Eligible subjects will receive repeat oral doses of GSK962040 given as 10 milligrams once daily tablet for 14 days.
Intervention: Placebo
Subjects receiving GSK962040 in cohort 2
Eligible subjects will receive repeat oral doses of GSK962040 given as 30 milligrams once daily tablet for 14 days.
Intervention: GSK962040
Subjects receiving GSK962040 in cohort 2
Eligible subjects will receive repeat oral doses of GSK962040 given as 30 milligrams once daily tablet for 14 days.
Intervention: Placebo
Subjects receiving GSK962040 in cohort 3
Eligible subjects will receive repeat oral doses of GSK962040 given as 100 milligrams once daily tablet for 14 days.
Intervention: GSK962040
Subjects receiving GSK962040 in cohort 3
Eligible subjects will receive repeat oral doses of GSK962040 given as 100 milligrams once daily tablet for 14 days.
Intervention: Placebo
Subjects receiving placebo in cohort 1, 2 and 3
Eligible subjects will receive repeat oral doses of placebo tablets given once daily for 14 days in cohort 1, 2 and 3.
Intervention: GSK962040
Subjects receiving placebo in cohort 1, 2 and 3
Eligible subjects will receive repeat oral doses of placebo tablets given once daily for 14 days in cohort 1, 2 and 3.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety, tolerability, and PK of GSK962040 from all adverse event reporting, 12-lead ECGs, vital signs, observation, safety laboratory tests and GI symptom diary; (AUC, Cmax, Tmax, accumulation ratio (Ro), half life and time invariance ratio (Rs)).
Secondary Outcomes
- Pharmacokinetic parameters following repeated oral doses of GSK962040 during a simulated liquid enteral feed meal: Cmax, Tmax, and AUC(0-t)
- Effect on gastric emptying.Effect of liquid meal on PK of GSK962040. Effect on bowel movement parameters
- Gastric emptying, as measured by the 13C octanoic acid breath test:Gastric half emptying time (t1/2b), Duration of the lag time (tlag), Gastric evacuation coefficient (GEC)
- Bowel movement parameters: Time to first bowel movement after first dose, Daily bowel movement count, Daily average bowel movement Bristol Stool Form scale
- Pharmacokinetic parameters following repeated every other day (QOD) oral doses of GSK962040: Cmax, Tmax, AUC(0-t), accumulation ratio (Ro), and, if possible, half-life, and time invariance ratio (Rs), as needed.