A Phase I, Randomized, Placebo-controlled, Double Blind, Repeat Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Gastrointestinal Transit Time and Pharmacodynamic Biomarkers of GSK3179106 in Normal Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: GSK3179106
* Drug: Matched Placebo


Participation Criteria
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Eligibility Criteria
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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 >1. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg of GSK3179106 QD-Cohort 1<br>Eligible six subjects will receive 10 mg oral dose once daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Experimental: 50 mg of GSK3179106 QD-Cohort 2<br>Eligible six subjects will receive 50 mg oral dose once daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Experimental: 200 mg of GSK3179106 QD-Cohort 3<br>Eligible six subjects will receive 200 mg oral dose once daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Experimental: 400 mg of GSK3179106 QD-Cohort 4<br>Eligible six subjects will receive 400 mg oral dose once daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Experimental: 25 mg of GSK3179106 BID-Cohort 5<br>Eligible six subjects will receive 25 mg oral dose twice daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Experimental: 200 mg of GSK3179106 BID-Cohort 6<br>Eligible six subjects will receive 200 mg oral dose twice daily for 14 days | Drug: GSK3179106<br>* It is uncoated round or oblong tablet with 3 strengths viz;. 5, 25 and 100 mg. It is White to slightly colored tablet and will be administered orally<br>|
| Placebo Comparator: Matching placebo QD-Cohort 1, 2, 3, 4<br>Eligible two subjects, per cohort, will receive oral dose of matched placebo once daily for 14 days | Drug: Matched Placebo<br>* It is uncoated round or oblong placebo tablet prepared to match actives across all strengths. It is White to slightly colored tablet and will be administered orally<br>|
| Placebo Comparator: Matching placebo BID-Cohort 5, 6<br>Eligible two subjects, per cohort, will receive oral dose of matched placebo twice daily for 14 days | Drug: Matched Placebo<br>* It is uncoated round or oblong placebo tablet prepared to match actives across all strengths. It is White to slightly colored tablet and will be administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse event (AE) | 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 | Up to Day 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REarranged during Transfection Growth Factor Receptor Tyrosine Kinase Inhibitor