Phase 1 Completed N=8 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT03154086 ↗

Enrolled (actual)

Serious AEs

1.0%

Results posted

Aug 2019

Primary outcomePrimary: Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 — 0; 1; 0; 0 Participants

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1	0; 1; 0; 0; 0; 3	—
PRIMARY Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2	0; 0; 0; 0; 1; 0	—
PRIMARY Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3	0; 0; 0; 2; 3; 1	—
PRIMARY Part B: Number of Participants With SAEs and Non-SAEs	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1	0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2	0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3	0; 0; 1	—
PRIMARY Part B: Number of Participants With Abnormal Findings After Physical Examination	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal ECG Findings in Cohort 2	0; 0; 0; 0; 0; 0	—
PRIMARY Part B: Number of Participants With Abnormal ECG Findings	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3	-1.25; -1.75; -2.08; 3.00; -2.70; 1.58	—
PRIMARY Part A: Change From Baseline in SBP and DBP in Cohort 2	3.75; 6.00; 3.75; -6.58; -1.75; -6.50	—
PRIMARY Part B: Change From Baseline in SBP and DBP	-4.70; -1.83; -2.33; 1.17; -2.33; -8.08	—
PRIMARY Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3	-3.79; -3.25; -3.00; -3.25; -4.00; -2.75	—
PRIMARY Part A: Change From Baseline in Pulse Rate in Cohort 2	1.50; 7.50; 0.42; 9.08; 1.75; -1.00	—
PRIMARY Part B: Change From Baseline in Pulse Rate	-1.55; -0.42; -2.25; -3.58; -1.17; -3.42	—
PRIMARY Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3	-0.09; 0.00; -0.22; -0.15; -0.12; 0.00	—
PRIMARY Part A: Change From Baseline in Body Temperature in Cohort 2	0.00; -0.10; 0.00; 0.00; 0.00; -0.10	—
PRIMARY Part B: Change From Baseline in Body Temperature	0.00; 0.00; 0.00; 0.00; 0.00; 0.00	—
PRIMARY Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1	0; 0; 0; 1; 0; 3	—
PRIMARY Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3	0; 0; 1; 0; 1; 0	—
PRIMARY Part B: Average BSFS at Indicated Time Points	3.17; 3.88; 3.92; 3.92; 4.13; 4.30	—
PRIMARY Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3	0.01; 0.00; 0.02; 0.00; 0.04; -0.03	—
PRIMARY Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2	0.00; 0.00; 0.00; 0.02; 0.05; 0.05	—
PRIMARY Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes	0.03; 0.00; 0.05; 0.03; 0.02; 0.02	—
PRIMARY Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3	0.029; 0.275; -0.073; 0.112; 0.120; 0.063	—
PRIMARY Part A: Change From Baseline in Erythrocytes in Cohort 2	0.110; 0.150; 0.167; 0.042	—
PRIMARY Part B: Change From Baseline in Erythrocytes	0.081; 0.208; 0.033; 0.230; -0.183; -0.023	—
PRIMARY Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3	0.0; 6.2; -2.5; 2.0; -0.8; 2.2	—
PRIMARY Part A: Change From Baseline in Hemoglobin in Cohort 2	4.0; 5.5; 5.8; 2.3	—
PRIMARY Part B: Change From Baseline in Hemoglobin	-1.8; 1.8; -5.3; 0.7; -6.7; 0.0	—
PRIMARY Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3	0.9; 0.2; 1.5; 1.7; 1.6; 0.8	—
PRIMARY Part A: Change From Baseline in Erythrocyte MCV in Cohort 2	-2.0; -2.0; 1.5; 0.7	—
PRIMARY Part B: Change From Baseline in Erythrocyte MCV	-1.4; 0.2; -2.7; -0.2; 0.2; -1.3	—
PRIMARY Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3	-0.19; -0.37; -0.13; -0.25; -0.84; 0.08	—
PRIMARY Part A: Change From Baseline in Erythrocyte MCH in Cohort 2	0.20; 0.20; 0.20; 0.27	—
PRIMARY Part B: Change From Baseline in Erythrocyte MCH	-0.87; -0.87; -1.25; -1.13; -0.28; 0.13	—
PRIMARY Part A: Change From Baseline in Hematocrit in Cohort 1 and 3	0.007; 0.025; 0.002; 0.017; 0.018; 0.007	—
PRIMARY Part A: Change From Baseline in Hematocrit in Cohort 2	0.005; 0.010; 0.023; 0.008	—
PRIMARY Part B: Change From Baseline in Hematocrit	0.000; 0.018; -0.012; 0.018; -0.017; -0.007	—
PRIMARY Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3	5.0; -1.8; -6.2; -1.2; -7.2; 6.0	—
PRIMARY Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2	-1.5; -0.5; 0.2; -2.3; -4.5; -1.5	—
PRIMARY Part B: Change From Baseline in ALT, AST and Alk Phos	-4.8; -7.7; -6.2; 2.3; -0.8; -0.3	—
PRIMARY Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3	1.2; 1.0; 1.2; 2.2; 1.6; -0.7	—
PRIMARY Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2	3.5; 2.0; 1.5; -0.7; -8.5; -8.0	—
PRIMARY Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin	2.4; 2.5; 3.2; 2.0; 2.0; 2.5	—
PRIMARY Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3	-0.049; -0.005; -0.075; -0.060; -0.054; -0.063	—
PRIMARY Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2	-0.075; -0.110; 0.022; -0.037; 0.35; 0.30	—
PRIMARY Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea	-0.001; 0.040; 0.108; 0.050; -0.045; -0.035	—
PRIMARY Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3	-3.1; -1.8; -3.5; -3.2; -4.8; -2.8	—
PRIMARY Part A: Change From Baseline in Albumin and Total Protein in Cohort 2	-1.0; -2.0; -1.2; -1.7; -2.5; -4.5	—
PRIMARY Part B: Change From Baseline in Albumin, Total Protein	-2.5; -2.3; -2.2; -3.3; -3.7; -0.8	—
PRIMARY Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3	0; 0; 0; 0; 0; 0	—
PRIMARY Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2	0; 0; 0; 0; 0; 0	—
PRIMARY Part B: Number of Participants With Abnormal Findings for Urine Parameters	0; 0; 0; 0; 0; 0	—
PRIMARY 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	0.8452; 1.306; 2.480; 4.630; 2.771; 2.030	—
PRIMARY 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	0.9652; 1.446; 2.738; 5.031; 3.648; 2.372	—
PRIMARY Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589	0.2339; 0.2919; 0.5541; 0.7318; 0.5397; 0.4317	—
PRIMARY Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589	1.25; 1.50; 1.00; 1.50; 1.25; 0.750	—
PRIMARY Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589	5.54; 7.83; 17.1; 17.0; 19.2; 20.5	—
PRIMARY Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect	0.5397; 0.4317	0.204
PRIMARY Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect	1.019; 0.7081	0.118
PRIMARY Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect	1.294; 0.8636	0.157
PRIMARY Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589	0.4479; 0.4647; 2.167; 3.459; 2.934; 0.7147	—
PRIMARY 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	1.389; 1.641; 7.285; 11.41; 12.31; 1.988	—
PRIMARY Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589	0.5028; 0.5468; 2.522; 4.055; 3.673; 0.8303	—
PRIMARY Part B: Cmax Following Repeat Dose Administration of GSK3352589	0.1308; 0.1394; 0.5255; 0.8191; 0.6607; 0.1655	—
PRIMARY Part B: Tmax Following Repeat Dose Administration of GSK3352589	0.767; 1.00; 1.00; 1.50; 0.750; 0.500	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03154086). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.