A Phase I, 14 Day, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Repeat Dose, Ascending Cohort Study to Evaluate the Safety, Tolerability Pharmacokinetics, Gastrointestinal Transit Time and Pharmacodynamic Biomarkers of GSK3179106, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- GSK3179106
- Conditions
- Irritable Bowel Syndrome
- Sponsor
- GlaxoSmithKline
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Number of subjects with adverse event (AE)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The current study is designed to assess the safety, tolerability, pharmacokinetics (PK), gastrointestinal (GI) transit time and pharmacodynamic (PD) biomarkers of repeat oral doses of GSK3179106 administered for 14 days in normal healthy subjects. It is a randomized, double-blind, placebo-controlled, ascending cohort study. A total of 48 subjects will be randomized (8 subjects/cohort) with 3:1 allocation to GSK3179106 or matching placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- •Healthy as determined by the investigator based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. History of regular bowel habits
- •Male or Female of non-childbearing potential.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions
Exclusion Criteria
- •ALT and bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>
- •ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Estimated Glomerular Filtration Rate \<60 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2)
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •History of Gastroesophageal reflux disease (GERD), dyspepsia, GI bleeding, GI surgery that could affect motility
Arms & Interventions
10 mg of GSK3179106 QD-Cohort 1
Eligible six subjects will receive 10 mg oral dose once daily for 14 days
Intervention: GSK3179106
50 mg of GSK3179106 QD-Cohort 2
Eligible six subjects will receive 50 mg oral dose once daily for 14 days
Intervention: GSK3179106
200 mg of GSK3179106 QD-Cohort 3
Eligible six subjects will receive 200 mg oral dose once daily for 14 days
Intervention: GSK3179106
400 mg of GSK3179106 QD-Cohort 4
Eligible six subjects will receive 400 mg oral dose once daily for 14 days
Intervention: GSK3179106
25 mg of GSK3179106 BID-Cohort 5
Eligible six subjects will receive 25 mg oral dose twice daily for 14 days
Intervention: GSK3179106
200 mg of GSK3179106 BID-Cohort 6
Eligible six subjects will receive 200 mg oral dose twice daily for 14 days
Intervention: GSK3179106
Matching placebo QD-Cohort 1, 2, 3, 4
Eligible two subjects, per cohort, will receive oral dose of matched placebo once daily for 14 days
Intervention: Matched Placebo
Matching placebo BID-Cohort 5, 6
Eligible two subjects, per cohort, will receive oral dose of matched placebo twice daily for 14 days
Intervention: Matched Placebo
Outcomes
Primary Outcomes
Number of subjects with adverse event (AE)
Time Frame: Up to Day 25
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product