Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects

NCT ID: NCT03874234

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2019-10-17

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and PK profile of single and repeat ascending doses of GSK3186899 in healthy subjects. This is a Phase 1 first time in human study, to investigate the effect of food on PK of GSK3186899. This study will consists of two parts. Part A (dose escalation phase) will be a single ascending, sequential cross-over design in cohorts 1, 2 and 3 of subjects. Cohort 1 and 2 will be 4-way cross-over which includes 4 dosing regimens of GSK3186899 and placebo (3:1 ratio) under fasted conditions. Cohort 3 will be 2-way cross-over which includes 2 treatment periods, 2 dosing regimens in fasted and fed conditions. In Part B (repeat dose escalation phase) subjects will be randomized to receive repeat doses of either GSK3186899 or placebo (3:1 ratio) in either fed or fasted conditions. Part B will be conducted based on the review of all safety, tolerability and PK data from Part A. The study duration includes screening, treatment periods and follow-up.

Conditions

Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: Subjects receiving GSK3186899 + placebo in Cohort 1

Subjects will receive 3 single ascending oral doses (SAD) of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 1 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

GSK3186899

Intervention Type: DRUG

GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Placebo

Intervention Type: DRUG

Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Part A: Subjects receiving GSK3186899 + placebo in Cohort 2

Subjects will receive 3 SAD of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 2 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.

Group Type: EXPERIMENTAL

GSK3186899

Intervention Type: DRUG

GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Placebo

Intervention Type: DRUG

Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Part A: Subjects receiving GSK3186899 in Cohort 3

Subjects will receive GSK3186899 orally, under fasted condition and fed conditions on Day 1 of cohort 3 in each of the two treatment periods. There will be a wash out period of at least 10 days between each treatment period. A dose level will be determined based on the effect of food on the safety, tolerability and PK of a single dose of GSK3186899, with dose level selected from Cohorts 1 and 2.

Group Type: EXPERIMENTAL

GSK3186899

Intervention Type: DRUG

GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Part B: Subjects receiving GSK3186899

Subjects will receive GSK3186899, orally, twice daily (BID) on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.

Group Type: EXPERIMENTAL

GSK3186899

Intervention Type: DRUG

GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Part B: Subjects receiving placebo

Subjects will receive placebo, orally, BID on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Interventions

GSK3186899

GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Intervention Type: DRUG

Placebo

Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m^2) (inclusive).
• Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP).
• Capable of giving signed informed consent.

• History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Previous history of leishmaniasis.
• ALT >1.5* upper limit of normal (ULN).
• Bilirubin >1.5*ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Current or past history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).
• ECG QT interval corrected for heart rate (QTc) >450 milliseconds (msec).
• Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton-pump inhibitors (PPIs) or anti-H2 antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the Investigator in consultation with the medical monitor.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates participation in the study.
• Regular use of known drugs of abuse.
• Subjects with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate glomerular filtration rate (GFR) <=80 (mL/minute/1.73m^2).
• Presence of Hepatitis B surface antigen (HBsAg) or Positive Hepatitis C antibody test result at screening.
• Positive human immunodeficiency virus (HIV) antibody test.
• Positive pre-study drug/alcohol screen.
• Presence of clinically significant hematuria and/or proteinuria.
• Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening.
• Part A (Food effect) Cohort 3 only: Subject must have no dietary restrictions (example, lactose intolerance) or inability to eat an adapted standard meal (includes 35-40 percent fat content).
• Part A (Food effect) Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (example, cholelithiasis) within 14 days prior to receiving the study treatment.
• Part B only: Early morning cortisol <420 nanomoles per liter (nmol/L) and inadequate response (rise of <250 millimoles per liter (mmol/L) from Baseline) to adrenocorticotropic hormone (ACTH) stimulation test at Day -1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

208436

Identifier Type: -

Identifier Source: org_study_id