Last updated: 06/17/2020 13:30:08

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

GSK study ID
209275
See study documents
Clinicaltrials.gov ID
NCT03627494
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Three-Part FTIH Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Oral Doses of GSK3439171A, in a Randomized, Double-Blind (sponsor unblinded), Placebo-Controlled, Dose Escalation study and to Evaluate the Effect of Food on a Single Oral Dose of GSK3439171A in Healthy Adult Participants
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Part A: Number of subjects with Adverse Events (AE) and Serious Adverse Events (SAE)

Timeframe: Up to 6 weeks

Part B: Number of subjects with AE and SAE

Timeframe: Up to 5 weeks

Part C: Number of subjects with AE and SAE

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Hematology Values

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Hematology Values

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Hematology Values

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Clinical Chemistry Values

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Clinical Chemistry Values

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Clinical Chemistry Values

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Urinalysis Values

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Urinalysis Values

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Urinalysis Values

Timeframe: Up to 4 weeks

Part B: Number of subjects with abnormal Hormone Assessment

Timeframe: Days -1 and 16

Part A: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure.

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure.

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure.

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Vital Signs: Pulse rate

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Vital Signs: Pulse rate

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Vital Signs: Pulse rate

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Vital Signs: Respiratory Rate

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Vital Signs: Respiratory Rate

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Vital Signs: Respiratory Rate

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Vital Signs: Oral temperature

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal Vital Signs: Oral temperature

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal Vital Signs: Oral temperature

Timeframe: Up to 4 weeks

Part A: Number of subjects with abnormal Electrocardiogram (ECG) findings

Timeframe: Up to 6 weeks

Part B: Number of subjects with abnormal ECG findings

Timeframe: Up to 5 weeks

Part C: Number of subjects with abnormal ECG findings

Timeframe: Up to 4 weeks

Part A: Area under the plasma drug concentration versus time curve (AUC(0-T) of GSK3439171A following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: AUC(0-T) of GSK3439171A following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part A: Area under the plasma drug concentration versus time curve (AUC(0-Inf) of GSK3439171A following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: AUC(0-Inf) of GSK3439171A following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part A: Maximum observed plasma drug concentration (Cmax) of GSK3439171A following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: Cmax of GSK3439171A following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK3439171A following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: Tmax of GSK3439171A following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part A: Apparent terminal half-life (t1/2) of GSK3439171A following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: t1/2 of GSK3439171A following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Secondary outcomes:

Part C: AUC(0-t) of GSK3439171A

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part C: AUC(0-inf) of GSK3439171A

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose

Part C: Cmax of GSK3439171A

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part C: Tmax of GSK3439171A

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part C: t1/2 of GSK3439171A in fed state

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part A: Dose proportionality of GSK3439171A using AUC (0-T) following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part A: Dose proportionality of GSK3439171A using AUC (0-Inf) following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part A: Dose proportionality of GSK3439171A using Cmax following Single dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period

Part B: Dose proportionality of GSK3439171A using AUC (0-tau) following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part B: Dose proportionality of GSK3439171A using Cmax following repeat dose

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part B: AUC (Ro) of GSK3439171A following repeat oral doses

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part B: Ratio of Cmax (RCmax) of GSK3439171A following repeat oral doses

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part B: Steady-state ratio (Rss) of GSK3439171A following repeat oral doses

Timeframe: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16

Part B: Trough plasma concentrations at the end of the dosing interval (Ctau) of GSK3439171A

Timeframe: Pre-dose on Days 15 and 16

Interventions:
  • Drug: GSK3439171A
  • Drug: Placebo
    • Enrollment:
    66
    Primary completion date:
    2019-26-08
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Muscular Dystrophies
    Product
    GSK3439171
    Collaborators
    Not applicable
    Study date(s)
    August 2018 to August 2019
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Male
    Age
    18 - 65 years
    Accepts healthy volunteers
    Yes
    • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
    • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • 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
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
    • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • 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
    Exclusion criteria:
    • 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.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Baltimore, Maryland, United States, 21225
    Status
    Study Complete
    Contact us

    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2019-26-08
    Actual study completion date
    2019-26-08

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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