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

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

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Drug: GSK3179106; Drug: Matched Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg of GSK3179106 QD-Cohort 1; Eligible six subjects will receive 10 mg oral dose once daily for 14 days	Drug: GSK3179106; 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
Experimental: 50 mg of GSK3179106 QD-Cohort 2; Eligible six subjects will receive 50 mg oral dose once daily for 14 days	Drug: GSK3179106; 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
Experimental: 200 mg of GSK3179106 QD-Cohort 3; Eligible six subjects will receive 200 mg oral dose once daily for 14 days	Drug: GSK3179106; 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
Experimental: 400 mg of GSK3179106 QD-Cohort 4; Eligible six subjects will receive 400 mg oral dose once daily for 14 days	Drug: GSK3179106; 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
Experimental: 25 mg of GSK3179106 BID-Cohort 5; Eligible six subjects will receive 25 mg oral dose twice daily for 14 days	Drug: GSK3179106; 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
Experimental: 200 mg of GSK3179106 BID-Cohort 6; Eligible six subjects will receive 200 mg oral dose twice daily for 14 days	Drug: GSK3179106; 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
Placebo Comparator: 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	Drug: Matched Placebo; 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
Placebo Comparator: Matching placebo BID-Cohort 5, 6; Eligible two subjects, per cohort, will receive oral dose of matched placebo twice daily for 14 days	Drug: Matched Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Cooper M, O'Connor-Semmes R, Reedy BA, Hacquoil K, Gorycki P, Pannullo K, Verticelli A, Shakib S. First-in-Human Studies for a Selective RET Tyrosine Kinase Inhibitor, GSK3179106, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Feb;8(2):234-245. doi: 10.1002/cpdd.600. Epub 2018 Sep 13.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 9, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: REarranged during Transfection Growth Factor Receptor Tyrosine Kinase Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome
• Other Study ID Numbers: 205181

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No