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

NCT02798991 | Completed Phase 1

• 1 other identifier: 205181
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Irritable Bowel Syndrome

Keywords

REarranged during Transfection Growth Factor Receptor Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (8)

10 mg of GSK3179106 QD-Cohort 1

EXPERIMENTAL

Eligible six subjects will receive 10 mg oral dose once daily for 14 days

Drug: GSK3179106

50 mg of GSK3179106 QD-Cohort 2

EXPERIMENTAL

Eligible six subjects will receive 50 mg oral dose once daily for 14 days

Drug: GSK3179106

200 mg of GSK3179106 QD-Cohort 3

EXPERIMENTAL

Eligible six subjects will receive 200 mg oral dose once daily for 14 days

Drug: GSK3179106

400 mg of GSK3179106 QD-Cohort 4

EXPERIMENTAL

Eligible six subjects will receive 400 mg oral dose once daily for 14 days

Drug: GSK3179106

25 mg of GSK3179106 BID-Cohort 5

EXPERIMENTAL

Eligible six subjects will receive 25 mg oral dose twice daily for 14 days

Drug: GSK3179106

200 mg of GSK3179106 BID-Cohort 6

EXPERIMENTAL

Eligible six subjects will receive 200 mg oral dose twice daily for 14 days

Drug: GSK3179106

Matching placebo QD-Cohort 1, 2, 3, 4

PLACEBO COMPARATOR

Eligible two subjects, per cohort, will receive oral dose of matched placebo once daily for 14 days

Drug: Matched Placebo

Matching placebo BID-Cohort 5, 6

PLACEBO COMPARATOR

Eligible two subjects, per cohort, will receive oral dose of matched placebo twice daily for 14 days

Drug: Matched Placebo

Interventions

GSK3179106 DRUG

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

10 mg of GSK3179106 QD-Cohort 1; 200 mg of GSK3179106 BID-Cohort 6; 200 mg of GSK3179106 QD-Cohort 3; 25 mg of GSK3179106 BID-Cohort 5; 400 mg of GSK3179106 QD-Cohort 4; 50 mg of GSK3179106 QD-Cohort 2

Matched Placebo DRUG

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

Matching placebo BID-Cohort 5, 6; Matching placebo QD-Cohort 1, 2, 3, 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

Related Publications (1)

• 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.

  PMID: 30277655 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2016
• First Posted: June 14, 2016
• Study Start: June 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: January 18, 2017

Record last verified: 2017-01

Locations

AU (1)