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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04472897
Recruitment Status : Recruiting
First Posted : July 16, 2020
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is a first time in human (FTIH) study to evaluate the safety, tolerability and pharmacokinetics (PK) of single and repeat ascending doses of GSK2556286 in healthy adult participants. Food effect (FE) cohorts will investigate the influence of food on the PK of GSK2556286. The study will be conducted in two parts. Part A will be a single ascending dose (SAD) including up to 11 cohorts (Cohort 1A to cohort 11A) and Part B will be a multiple ascending dose (MAD), including up to 4 cohorts (Cohort 1B to cohort 4B).

Condition or disease Intervention/treatment Phase
Tuberculosis Drug: GSK2556286 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is a double-blind, randomized, sequential, parallel dose cohort study.
Masking: Double (Participant, Investigator)
Masking Description: This is a double-blind study.
Primary Purpose: Treatment
Official Title: A Randomised, 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
Actual Study Start Date : October 30, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Arm Intervention/treatment
Experimental: Part A: Participants receiving GSK2556286
Participants will be randomized to receive GSK2556286 in any of the 11 cohorts. In each dosing cohort, 6 participants will receive a single dose of GSK2556286. Following initial dosing of cohorts in the fasted state, one cohort will investigate the effect of food administration (high fat meal) on safety, tolerability and PK data of GSK2556286. One cohort may also investigate the effects of a moderate fat meal.
Drug: GSK2556286
GSK2556286 will be administered.

Placebo Comparator: Part A: Participants receiving placebo
Participants will be randomized to receive matching placebo in any of the 11 cohorts. In each dosing cohort, 2 participants will receive a single dose of matching placebo.
Drug: Placebo
Placebo will be administered

Experimental: Part B: Participants receiving GSK2556286

Participants will be randomized to receive GSK2556286 in any of the 4 cohorts. In each dosing cohort, 6 participants will receive repeat doses of GSK2556286 under either fasting or fed conditions, dependent on the results from Part A.

Appropriate doses and dose regimens for Part B will be selected by the Dose Escalation Committee based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B.

Drug: GSK2556286
GSK2556286 will be administered.

Placebo Comparator: Part B: Participants receiving placebo
Participants will be randomized to receive matching placebo in any of the 4 cohorts. In each dosing cohort, 2 participants will receive repeat doses of matching placebo under either fasting or fed conditions, dependent on the results from Part A.
Drug: Placebo
Placebo will be administered




Primary Outcome Measures :
  1. Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs [ Time Frame: Up to Day 15 ]
  2. Part B: Number of participants with any SAEs and non-SAEs [ Time Frame: Up to Day 28 ]
  3. Part A: Number of participants with AEs (SAEs and non-SAEs) by severity [ Time Frame: Up to Day 15 ]
  4. Part B: Number of participants with AEs (SAEs and non-SAEs) by severity [ Time Frame: Up to Day 28 ]
  5. Part A: Plasma concentrations of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  6. Part A: Area under the plasma drug concentration versus time curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  7. Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  8. Part A: Maximum observed plasma drug concentration (Cmax) of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  9. Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  10. Part A: Apparent terminal half-life (T1/2) of GSK2556286 [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  11. Part B: Plasma concentrations of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose. Day 12 and 13: Pre-dose ]
  12. Part B: AUC(0-t) of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  13. Part B: AUC(0-inf) of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  14. Part B: Area under the plasma drug concentration versus time curve from time zero during a dosage interval of time tau (AUC[0-tau)] of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  15. Part B: Cmax of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  16. Part B: Tmax of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  17. Part B: Trough plasma concentration (Ctau) of GSK2556286 [ Time Frame: Pre-dose on Days 1, 12, 13 and 14 ]
  18. Part B: T1/2 of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]

Secondary Outcome Measures :
  1. Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  2. Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  3. Part A: Cmax of GSK2556286 under fasted and fed conditions [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  4. Part A: Tmax of GSK2556286 under fasted and fed conditions [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  5. Part A: T1/2 of GSK2556286 under fasted and fed conditions [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  6. Part A: Dose proportionality of GSK2556286 based on AUC(0-inf) [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  7. Part A: Dose proportionality of GSK2556286 based on AUC(0-t) [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  8. Part A: Dose proportionality of GSK2556286 based on Cmax [ Time Frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  9. Part B: Dose proportionality of GSK2556286 based on AUC(0-tau) [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  10. Part B: Dose proportionality of GSK2556286 based on Cmax [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  11. Part B: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro]) [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  12. Part B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax) [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  13. Part B: Steady state ratio (Rss) of GSK2556286 [ Time Frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose ]
  14. Part B: Ctau at the end of the dosing interval to assess steady state of GSK2556286 [ Time Frame: Pre-dose on Days 1, 12, 13 and 14 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent. Participants aged 51 to 60 years must have received at least one dose of Coronavirus disease-2019 (COVID-19) vaccine approved by the local regulatory authority at least 3 weeks prior to signing the consent form.
  • Participants who are 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) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the Investigator considers and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight more than or equal to (>=)50 kilograms (kg) and body mass index (BMI) within the range 19 to 29.9 kilograms per meter square (kg/m^2) inclusive.
  • Male and/or Female Participants. A male participant with a female partner of reproductive potential must agree to use contraception of this 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 is eligible to participate if she is not a woman of childbearing potential (WONCBP).
  • The participant is 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.
  • Alanine aminotransferase (ALT) greater than (>)1.5 times upper limit of normal (ULN).
  • Total bilirubin >1.5 times ULN (isolated total bilirubin >1.5 times ULN may be acceptable, after consultation with the GlaxoSmithKline (GSK) Medical Monitor, if total bilirubin is fractionated and direct bilirubin less than [<]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) 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:

    1. Heart rate of <40 or >100 beats per minute (bpm) in males and <50 or >100 bpm in females.
    2. PR interval of <120 or >220 milliseconds (msec) in males and females.
    3. QRS duration of <70 or >120 msec in males and females.
    4. 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 (does not include 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, will interfere with the safety for the individual participant.
  • Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
  • Evidence of latent tuberculosis documented by:

    1. medical history and examination.
    2. 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 is 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 (+) is found on urine dipstick, a repeat test can be performed. If repeat is positive, participant is 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 has taken part 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: 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 no relevant dietary restrictions (lactose intolerance) or inability to eat a high fat meal.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04472897


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Netherlands
GSK Investigational Site Completed
Groningen, Netherlands, 9713 AG
United Kingdom
GSK Investigational Site Recruiting
Cambridge, United Kingdom, CB2 2GG
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Edward Banham-Hall         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04472897    
Other Study ID Numbers: 210035
First Posted: July 16, 2020    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study, a key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK2556286
Pharmacokinetics
Interventional
Tuberculosis
Placebo-controlled
FTIH
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections