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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Irritable Bowel Syndrome

Treatments: Drug: GSK3352589; Drug: Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03154086

207440

Details and patient eligibility

About

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.

Enrollment: 68 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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68 participants in 11 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Part A: Cohort 2: Placebo Fasted/Placebo Fed

Experimental group

Description:

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.

Treatment:

Drug: Matching Placebo

Part A:Cohort 3: GSK3352589 150 mg/Placebo

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

Part A:Cohort 3: Placebo/GSK3352589 400 mg

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Drug: Matching Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Part B: GSK3352589

Experimental group

Description:

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.

Treatment:

Drug: GSK3352589

Part B: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Matching Placebo