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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

Primary Purpose

Irritable Bowel Syndrome

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

GSK3179106

Matched Placebo

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome focused on measuring REarranged during Transfection Growth Factor Receptor Tyrosine Kinase Inhibitor

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 >1.5xupper 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

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 Type

Experimental

Placebo Comparator

Arm Label

10 mg of GSK3179106 QD-Cohort 1

50 mg of GSK3179106 QD-Cohort 2

200 mg of GSK3179106 QD-Cohort 3

400 mg of GSK3179106 QD-Cohort 4

25 mg of GSK3179106 BID-Cohort 5

200 mg of GSK3179106 BID-Cohort 6

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

Matching placebo BID-Cohort 5, 6

Arm Description

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02798991

First Posted

June 9, 2016

Last Updated

January 16, 2017

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT02798991

Brief Title

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

Official Title

A Phase I, 14 Day, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Repeat Dose, Ascending Cohort Study to Evaluate the Safety, Tolerability Pharmacokinetics, Gastrointestinal Transit Time and Pharmacodynamic Biomarkers of GSK3179106, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

June 2016 (undefined)

Primary Completion Date

November 2016 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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 Growth Factor Receptor Tyrosine Kinase Inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

46 (Actual)

8. Arms, Groups, and Interventions

Arm Title

10 mg of GSK3179106 QD-Cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

50 mg of GSK3179106 QD-Cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

200 mg of GSK3179106 QD-Cohort 3

Arm Type

Experimental

Arm Description

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

Arm Title

400 mg of GSK3179106 QD-Cohort 4

Arm Type

Experimental

Arm Description

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

Arm Title

25 mg of GSK3179106 BID-Cohort 5

Arm Type

Experimental

Arm Description

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

Arm Title

200 mg of GSK3179106 BID-Cohort 6

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Matching placebo BID-Cohort 5, 6

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

GSK3179106

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Matched Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of subjects with adverse event (AE)

Description

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

Time Frame

Up to Day 25

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 >1.5xupper 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

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

Citations:

PubMed Identifier

30277655

Citation

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.

Results Reference

derived

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