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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Irritable Bowel Syndrome

Treatments: Drug: Matched Placebo; Drug: GSK3179106

Study type: Interventional

Funder types: Industry

Identifiers

NCT02798991

205181

Details and patient eligibility

About

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.

Enrollment: 46 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 >1.5xupper 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 8 patient groups, including a placebo group

10 mg of GSK3179106 QD-Cohort 1

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

50 mg of GSK3179106 QD-Cohort 2

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

200 mg of GSK3179106 QD-Cohort 3

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

400 mg of GSK3179106 QD-Cohort 4

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

25 mg of GSK3179106 BID-Cohort 5

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

200 mg of GSK3179106 BID-Cohort 6

Experimental group

Description:

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

Treatment:

Drug: GSK3179106

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Matched Placebo

Matching placebo BID-Cohort 5, 6

Placebo Comparator group

Description:

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

Treatment:

Drug: Matched Placebo