A Phase 1, First Time in Human (FTIH) Study to Evaluate GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Volunteers

NCT ID: NCT03154086

Last Updated: 2019-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-17
• Study Completion Date: 2018-03-05

Brief Summary

This FTIH study is designed to assess the safety, tolerability and pharmacokinetic (PK) of escalating single and repeat oral doses of GSK3352589 in normal healthy volunteers. This is a randomized, double-blind (sponsor unblinded), placebo controlled, dose escalation study that will have two parts; Part A and Part B.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg

Subjects will receive single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg

Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg

Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo

Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed

Subjects will receive single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Part A: Cohort 2: Placebo Fasted/Placebo Fed

Subjects will receive single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 3: GSK3352589 150 mg/Placebo

Subjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 3: Placebo/GSK3352589 400 mg

Subjects will receive single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg

Subjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Part B: GSK3352589

Subjects will receive repeat oral doses of GSK3352589 of 5 mg, 15 mg, 50 mg, 100 mg or 200 mg twice daily administered for 14 days.

Group Type: EXPERIMENTAL

GSK3352589

Intervention Type: DRUG

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Part B: Placebo

Subjects will receive repeat oral doses of placebo twice a day tablet administered for 14 days.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Interventions

GSK3352589

It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.

Intervention Type: DRUG

Matching Placebo

It will be available across all strengths to match active drug in the form of tablet for oral administration.

Intervention Type: DRUG

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 >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Previous Diagnosis of IBS
• Estimated Glomerular Filtration Rate <60 millilter 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, Gastrointestinal (GI) bleeding, diverticulitis, diverticular stricture or other intestinal strictures, GI surgery that could affect motility
• Unwillingness or inability to follow the procedures outlined in the protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Adelaide, South Australia, Australia

Countries

Australia

References

Reedy BA, O'Connor-Semmes R, Hacquoil K, Gorycki P, Verticelli A, Molga A. First-in-Human Study for a Selective Rearranged During Transfection Tyrosine Kinase Inhibitor, GSK3352589, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Apr;10(4):334-345. doi: 10.1002/cpdd.911. Epub 2021 Feb 19.

Reference Type: DERIVED

PMID: 33606922 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

207440

Identifier Type: -

Identifier Source: org_study_id