First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect

NCT ID: NCT03627494

Last Updated: 2020-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-30
• Study Completion Date: 2019-08-26

Brief Summary

The FTIH study with GSK3439171A will evaluate the safety of GSK3439171A in healthy subjects in order to avoid confounding factors due to the disease or concomitant drugs in patients. The study design is based on pre-clinical findings for GSK3439171A, contributing to the frequency, type and duration of safety assessment and monitoring during treatment periods in each cohort. The single dose assessments in Part A will be conducted to determine safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the study intervention in individuals before progressing to doses explored further in other parts of the study and will allow for any adjustments needed based on emerging safety, tolerability, and PK information. Part A will also serve to identify a dose for use in examining the effect of food on GSK3439171A exposure in Part C. In Part B, a single dose safety, tolerability and PK will be collected followed by progression of these subjects to the repeat dose portion of the study. The up to 14-day dosing was chosen as it is thought to provide sufficient safety and tolerability data to bridge to longer duration studies. The dosing period can be adjusted depending on PK and PD data collected in Part A of the study. Part B will involve more detailed PK/PD/metabolite assessments to better understand the impact of GSK3439171A on target engagement and metabolism in humans. Approximately 150 subjects will be screened to achieve 75 randomly assigned to study intervention. Duration for Part A, B and C will be approximately 10 weeks, 9 weeks and 8 weeks respectively.

Conditions

Muscular Dystrophies

Study Design

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

Study Groups

Part A: P1,PBO/GSK3439171A Dose 2/GSK3439171A Dose 3

Subjects will administer oral solution with doses 0.5 milligram (mg) up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence placebo (PBO) followed by Dose 2 of GSK3439171A followed by Dose 3 of GSK3439171A in period 1 (P1). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P1, GSK3439171A Dose 1/ PBO/GSK3439171A Dose 3

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and PBO as per randomized sequence: Dose 1 of GSK3439171A followed by PBO followed by Dose 3 of GSK3439171A in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P1, GSK3439171A Dose 1/ GSK3439171A Dose 2/ PBO

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 1 of GSK3439171A followed by Dose 2 of GSK3439171A followed by PBO in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P2, PBO/GSK3439171A Dose 5/GSK3439171A Dose 6

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 5 of GSK3439171A followed by Dose 6 of GSK3439171A in period 2 (P2). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P2, GSK3439171A Dose 4/ PBO/GSK3439171A Dose 6

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by PBO followed by Dose 6 of GSK3439171A in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P2, GSK3439171A Dose 4/ GSK3439171A Dose 5/ PBO

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by Dose 5 of GSK3439171A followed by PBO in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P3, PBO/GSK3439171A Dose 8/GSK3439171A Dose 9

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 8 of GSK3439171A followed by Dose 9 of GSK3439171A in Period 3 (P3). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P3, GSK3439171A Dose 7/ PBO/GSK3439171A Dose 9

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by PBO followed by Dose 9 of GSK3439171A in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P3, GSK3439171A Dose 7/ GSK3439171A Dose 8/ PBO

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by Dose 8 of GSK3439171A followed by PBO in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part B: GSK3439171A

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A in part B

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part B: Placebo

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of Placebo in part B

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part C: GSK3439171A fed followed by GSK3439171A fasted

Subjects will administer GSK3439171A in Fed condition in Part C P1 followed by GSK3439171A in fasted condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part C: GSK3439171A fasted followed by GSK3439171A fed

Subjects will administer GSK3439171A in fasted condition in Part C P1 followed by GSK3439171A in fed condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Group Type: EXPERIMENTAL

GSK3439171A

Intervention Type: DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo

Intervention Type: DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Interventions

GSK3439171A

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Intervention Type: DRUG

Placebo

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Subjects with Body weight >=50.0 kilograms (Kg) (110 lbs.) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per square meter (inclusive).
• Only male subjects are eligible for this study. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male subjects are eligible to participate if they agree to the following during the their entire enrolment in the study plus an additional 5 days or 5 terminal half-lives (whichever is longer): Refrain from donating sperm plus either be abstinent from sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier (female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year)
• Subjects must be capable of giving signed informed consent

• Subjects are excluded from the study if they have history or presence of 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 intervention; or interfering with the interpretation of data.
• Subjects are excluded from the study if they have any clinically significant abnormal vital signs
• Subjects are excluded from the study if they have Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• Subjects are excluded from the study if they have ALT >1.5 times upper limit of normal (ULN)
• Subjects are excluded from the study if Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Subjects are excluded from the study if they have current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects are excluded from the study if they have QTc >450 milliseconds
• Subjects who are unable to refrain from the use of prescription or non-prescription drugs, including aspirin, Non-steroidal Anti-inflammatory Drugs (NSAIDs), vitamins, herbal and dietary supplements (including St John's Wort) within 10 days prior to the first dose of study medication.
• In cases, where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days
• Subjects with exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Subjects with current enrolment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
• Subjects with presence of Hepatitis B surface antigen (HBsAg) at screening.
• Subjects with Positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
• Subjects with Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
• Subjects with positive pre-study drug/alcohol screen
• Subjects with positive human immunodeficiency virus (HIV) antibody test
• Subjects with regular use of known drugs of abuse or positive urine drug test at screening or each in-house admission to the clinical research unit
• Subjects with regular alcohol consumption within 6 months prior to screening and 5 days prior to admission defined as: An average weekly intake of > 14 units for males. One unit is equivalent to 8 gram of alcohol: a half-pint (Approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of 80 proof distilled spirits
• Subjects with positive urinary cotinine test indicative of smoking history at screening or each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening
• Subjects with sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• 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

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

209275

Identifier Type: -

Identifier Source: org_study_id