Last updated: 11/07/2025 08:58:01

A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK2556286 in Healthy Adult Participants

GSK study ID
210035
See study documents
Clinicaltrials.gov ID
NCT04472897
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, First-Time-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Oral Doses and the Food Effect of GSK2556286 in Healthy Adult Participants
Trial description: This first time in human (FTIH) study assesses the safety, tolerability, and
pharmacokinetics (PK) of single and multiple increasing doses of GSK2556286. It also
includes food effect cohorts to evaluate how food influences the PK of GSK2556286. The
findings will help determine appropriate dosing for future clinical studies.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with serious adverse events (SAEs) overall and by severity

Timeframe: From the date of informed consent signing (up to 28 days prior to Day 1) through 14 days after the dose administration

Number of participants with non-SAEs overall and by severity

Timeframe: From Day 1 (first dose) up to 14 days after the dose administration

Cohort A: Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK2556286 following single dose administration

Timeframe: Pre-dose, 0.25 hour (h), 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1

Cohort A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286 following single dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1

Cohort A: Maximum observed plasma drug concentration (Cmax) of GSK2556286

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1

Cohort A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286 following single dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1

Cohort A: Apparent terminal half-life (t1/2) of GSK2556286 following single dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1

Cohort B: AUC(0-t) of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Cohort B: AUC(0-inf) of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Cohort B: AUC versus time curve from time zero during a dosage interval of time [AUC(0-tau)] of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Cohort B: Cmax of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Cohort B: Tmax of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Cohort B: Trough plasma concentration (Ctau) of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h, 24h (D2 pre-dose), 36h (D2), 48h (D3 pre-dose),72h post-dose on D1 and D14; Pre-dose, 0.25 h, 0.5h, 0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h, 24h post-dose on D9 and D11; Pre-dose on Days 6, 7, 8

Cohort B: t1/2 of GSK2556286 following multiple dose administration

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 1 and Day 14; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11

Secondary outcomes:

Cohort A: AUC(0-t) of GSK2556286 following single dose administration under fasted and fed conditions

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: AUC(0-inf) of GSK2556286 following single dose administration under fasted and fed conditions

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: Cmax of GSK2556286 following single dose administration under fasted and fed conditions

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: Tmax of GSK2556286 following single dose administration under fasted and fed conditions

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: t1/2 of GSK2556286 following single dose administration under fasted and fed conditions

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort B: AUC(0-t) of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: AUC(0-inf) of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: AUC(0-tau) of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: Cmax of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: Tmax of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: Ctau of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort B: t1/2 of GSK2556286 following multiple dose administration under fasted and fed conditions

Timeframe: Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h and 24h post-dose on Day 9 and Day 11; Pre-dose, 0.25 h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 15h, 24h, 36h, 48h and 72h post-dose on Day 14

Cohort A: Dose-proportionality assessment using AUC(0-inf) following a single dose of GSK2556286

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: Dose-proportionality assessment using AUC(0-t) following a single dose of GSK2556286

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort A: Dose-proportionality assessment using Cmax following a single dose of GSK2556286

Timeframe: At pre-dose and 0.25 hour (h), 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 15 h, 24 h, 36 h, 48 h and 72 h post-dose on Day 1

Cohort B: Dose-proportionality assessment using AUC(0-tau) following multiple doses of GSK2556286

Timeframe: Pre-dose and at 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1;Pre-dose and 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14

Cohort B: Dose-proportionality assessment using Cmax following multiple doses of GSK2556286

Timeframe: Pre-dose and at 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1;Pre-dose and 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14

Cohort B: Observed accumulation ratio (R) of GSK2556286 for AUC [AUC(Ro)] following multiple doses of GSK2556286

Timeframe: Pre-dose and 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14 compared to Pre-dose and at 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1

Cohort B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax) following multiple doses of GSK2556286

Timeframe: Pre-dose and 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14 compared to Pre-dose and at 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1

Cohort B: Observed accumulation ratio of GSK2556286 based on steady state ratio (Rss) following multiple doses of GSK2556286

Timeframe: Pre-dose and 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14 compared to Pre-dose and at 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1

Cohort B: Ctau at the end of the dosing interval to assess steady state following multiple doses of GSK2556286

Timeframe: Pre-dose and 0.25 hour(h),0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,15h,24h,36h,48h and 72h post-dose on Day 14 compared to Pre-dose and at 0.25h,0.5h,0.75h,1h,1.5h,2h,3h,4h,6h,8h,12h,12.25h,12.5h,12.75h,13h,13.5h,14h,15h,16h and 24h post-dose on Day 1

Interventions:
  • Drug: GSK2556286
  • Drug: Placebo
    • Enrollment:
    92
    Primary completion date:
    2024-06-11
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Tuberculosis
    Product
    Not applicable
    Collaborators
    Not applicable
    Study date(s)
    October 2020 to November 2024
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 60 Years
    Accepts healthy volunteers
    Yes
    • Participants had to be 18 to 60 years of age inclusive at the time of signing the
    • informed consent. Participants aged 51 to 60 years had to have received at least one
    • Significant history of or current, cardiovascular, respiratory (including asthma),
    • hepatic, renal, gastrointestinal, endocrine, hematological, infectious or neurological
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Participants had to be 18 to 60 years of age inclusive at the time of signing the informed consent. Participants aged 51 to 60 years had to have received at least one dose of a Coronavirus disease-2019 (COVID-19) vaccine approved by the local regulatory authority at least 3 weeks prior to signing the consent form.
    • Participants had to be overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the inclusion or exclusion criteria, but outside the normal reference range for the population being studied, could be included only if the Investigator considered and documented that the finding was unlikely to introduce additional risk factors and would not interfere with the study procedures.
    • Participants had to have a body weight greater than or equal to (≥) 50 kilograms (kg) and a body mass index (BMI) within the range of 19 to 29.9 kilograms per meter square (kg/m²) inclusive.
    • Male and/or female participants were eligible. A male participant with a female partner of reproductive potential had to agree to use contraception as per the clinical study protocol 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 participant was eligible to participate if she was not a woman of childbearing potential (WONCBP).
    • Participants had to be able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions.
    Exclusion criteria:
    • Significant history of or current, cardiovascular, respiratory (including asthma), hepatic, renal, gastrointestinal, endocrine, hematological, infectious or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs: constituting a risk when taking part in the study or interfering with the interpretation of data.
    • Participants with alanine aminotransferase (ALT) greater than (>)1.5 times upper limit of normal (ULN).
    • Participants with total bilirubin >1.5 times ULN (isolated total bilirubin >1.5 times ULN could have been acceptable, after consultation with the GSK Medical Monitor, if total bilirubin was fractionated and direct bilirubin was less than [<] 35%).
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or cholecystectomy.
    • Current or past history of significant renal disease including renal stones.
    • Current or past history of gastroduodenal ulcers or persistent gastritis requiring medication.
    • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
    • Exclusion criteria for screening electrocardiogram (ECG) with: (a) Heart rate of <40 or >100 beats per minute (bpm) in males and <50 or >100 bpm in females. (b) PR interval of <120 or >220 milliseconds (msec) in males and females. (c) QRS duration of <70 or >120 msec in males and females. (d) Electrocardiogram QT interval corrected for heart rate using Fridericia’s formula (QTcF) interval of >450 msec in males and females.
    • Evidence of previous myocardial infarction (excluding ST segment changes associated with re-polarization).
    • Any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [second degree or higher], Wolff -Parkinson-White [WPW] syndrome).
    • Sinus pauses >3 seconds.
    • Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical monitor, would have interfered with the safety of the individual participant.
    • Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
    • Evidence of latent tuberculosis documented by: (a) medical history and examination. (b) Tuberculosis (TB) testing : either a positive tuberculin skin test (TST) (defined as a skin induration >5 millimeters [mm] at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) TB test such as QuantiFERON-TB Gold Plus test. In cases where the QuantiFERON or TST is indeterminate, the participant may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or TST test is positive, the participant should be followed up as per standard of care.
    • Use of prescription or non-prescription drugs, including Nonsteroidal anti-inflammatory drugs (NSAIDs), high-dose vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
    • Cotinine in urine indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months.
    • Current regular alcohol consumption defined as an average weekly intake of >21 units for males or >14 units for females. One unit was equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
    • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
    • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
    • A positive test for human immunodeficiency virus (HIV) antibody.
    • Urinary analysis indicating presence of blood, protein or glucose. If trace or 1 plus (+) was found on urine dipstick, a repeat test could be performed. If repeat is positive, participant was excluded from recruitment.
    • Screening age-appropriate estimated glomerular filtration rate (eGFR) <90 milliliters per minute mL/min as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
    • Serum (and in the MAD, urinary) electrolytes outside of normal range. May be repeated once if abnormal.
    • A positive pre-study drug/alcohol screen.
    • The participant had taken part in a clinical trial and had received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
    • Part A (Food Effect) Cohort: Participant must have had no relevant dietary restrictions (lactose intolerance) or inability to eat a high fat meal.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    GRONINGEN, Netherlands, 9713 AG
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Cambridge, United Kingdom, CB2 2GG
    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
    Other
    Actual primary completion date
    2024-06-11
    Actual study completion date
    2024-06-11

    Plain language summaries

    Summary of results in plain language
    Available language(s): English, Dutch
    Download document(s)

    To view plain language summaries on trialsummaries.com click here.

    Additional information about the trial

    Additional information
    Not applicable
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