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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

Primary Purpose

Irritable Bowel Syndrome

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

GSK3352589

Matching Placebo

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome focused on measuring REarranged during Transfection

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts 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

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Placebo Comparator

Arm Label

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

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

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

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

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

Part A: Cohort 2: Placebo Fasted/Placebo Fed

Part A:Cohort 3: GSK3352589 150 mg/Placebo

Part A:Cohort 3: Placebo/GSK3352589 400 mg

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

Part B: GSK3352589

Part B: Placebo

Arm 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Outcomes

Primary Outcome Measures

Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.

Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.

Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3

Part B: Number of Participants With SAEs and Non-SAEs

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1

A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2

A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3

Part B: Number of Participants With Abnormal Findings After Physical Examination

Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3

Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented.

Part A: Number of Participants With Abnormal ECG Findings in Cohort 2

Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.

Part B: Number of Participants With Abnormal ECG Findings

Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.

Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3

Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in SBP and DBP in Cohort 2

Part B: Change From Baseline in SBP and DBP

Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3

Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Pulse Rate in Cohort 2

Part B: Change From Baseline in Pulse Rate

Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3

Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Body Temperature in Cohort 2

Part B: Change From Baseline in Body Temperature

Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1

The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).

Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2

Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3

Part B: Average BSFS at Indicated Time Points

Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3

Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2

Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes

Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3

Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythrocytes in Cohort 2

Part B: Change From Baseline in Erythrocytes

Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3

Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Hemoglobin in Cohort 2

Part B: Change From Baseline in Hemoglobin

Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3

Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythrocyte MCV in Cohort 2

Part B: Change From Baseline in Erythrocyte MCV

Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3

Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Erythrocyte MCH in Cohort 2

Part B: Change From Baseline in Erythrocyte MCH

Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Hematocrit in Cohort 1 and 3

Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Hematocrit in Cohort 2

Part B: Change From Baseline in Hematocrit

Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3

Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2

Part B: Change From Baseline in ALT, AST and Alk Phos

Blood samples were collected for analysis of hematology parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3

Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2

Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin

Blood samples were collected for analysis of hematology parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3

Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2

Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea

Blood samples were collected for analysis of hematology parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3

Blood samples were collected for analysis of clinical chemistry parameters including albumin, and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Change From Baseline in Albumin and Total Protein in Cohort 2

Blood samples were collected for analysis of clinical chemistry parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part B: Change From Baseline in Albumin, Total Protein

Blood samples were collected for analysis of hematology parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3

Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable).

Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2

Part B: Number of Participants With Abnormal Findings for Urine Parameters

Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. The PK Parameter population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study.

Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including t1/2 following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect

Blood samples were collected from participants for pharmacokinetic analysis following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.

Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589

Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-24) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.

Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.

Part B: Cmax Following Repeat Dose Administration of GSK3352589

Part B: Tmax Following Repeat Dose Administration of GSK3352589

Secondary Outcome Measures

Full Information

NCT ID

NCT03154086

First Posted

May 12, 2017

Last Updated

June 28, 2019

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT03154086

Brief Title

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

Official Title

A Phase I, First Time in Human, Two Part, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Single and Repeat Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

May 17, 2017 (Actual)

Primary Completion Date

March 5, 2018 (Actual)

Study Completion Date

March 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Irritable Bowel Syndrome

Keywords

REarranged during Transfection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

68 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Part A: Cohort 2: Placebo Fasted/Placebo Fed

Arm Type

Experimental

Arm Description

Arm Title

Part A:Cohort 3: GSK3352589 150 mg/Placebo

Arm Type

Experimental

Arm Description

Arm Title

Part A:Cohort 3: Placebo/GSK3352589 400 mg

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Part B: GSK3352589

Arm Type

Experimental

Arm 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.

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

GSK3352589

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matching Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1

Description

Time Frame

Up to 64 days in Cohort 1

Title

Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2

Description

Time Frame

Up to 30 days in Cohort 2

Title

Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3

Description

Time Frame

Up to 30 days in Cohort 3

Title

Part B: Number of Participants With SAEs and Non-SAEs

Description

Time Frame

Up to 25 days

Title

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1

Description

Time Frame

Up to 64 days in Cohort 1

Title

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2

Description

Time Frame

Up to 30 days in Cohort 2

Title

Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3

Description

Time Frame

Up to 30 days in Cohort 3

Title

Part B: Number of Participants With Abnormal Findings After Physical Examination

Description

Time Frame

Up to 25 days

Title

Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2

Title

Part A: Number of Participants With Abnormal ECG Findings in Cohort 2

Description

Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2

Title

Part B: Number of Participants With Abnormal ECG Findings

Description

Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25)

Title

Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part A: Change From Baseline in SBP and DBP in Cohort 2

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part B: Change From Baseline in SBP and DBP

Description

Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)

Title

Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part A: Change From Baseline in Pulse Rate in Cohort 2

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part B: Change From Baseline in Pulse Rate

Description

Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Title

Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part A: Change From Baseline in Body Temperature in Cohort 2

Description

Time Frame

Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3

Title

Part B: Change From Baseline in Body Temperature

Description

Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Title

Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1

Description

Time Frame

Up to 64 days in Cohort 1

Title

Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2

Description

Time Frame

Up to 30 days in Cohort 2

Title

Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3

Description

Time Frame

Up to 30 days in Cohort 3

Title

Part B: Average BSFS at Indicated Time Points

Description

Time Frame

Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14

Title

Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes

Description

Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Erythrocytes in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Erythrocytes

Description

Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Hemoglobin in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Hemoglobin

Description

Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Erythrocyte MCV in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Erythrocyte MCV

Description

Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Erythrocyte MCH in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Erythrocyte MCH

Description

Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Hematocrit in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Hematocrit in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Hematocrit

Description

Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in ALT, AST and Alk Phos

Description

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin

Description

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea

Description

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part A: Change From Baseline in Albumin and Total Protein in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Change From Baseline in Albumin, Total Protein

Description

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3

Description

Time Frame

Baseline (Day-1) and Day 3

Title

Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2

Description

Time Frame

Baseline (Day -1) and Day 3

Title

Part B: Number of Participants With Abnormal Findings for Urine Parameters

Description

Time Frame

Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)

Title

Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose

Title

Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

Title

Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

Title

Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

Title

Part B: Cmax Following Repeat Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

Title

Part B: Tmax Following Repeat Dose Administration of GSK3352589

Description

Time Frame

Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33606922

Citation

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.

Results Reference

derived

Learn more about this trial

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

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