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TuberculosisPhase 1NCT04472897

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

A Phase 1 study testing GSK2556286 in people with Tuberculosis, run by GlaxoSmithKline at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Tuberculosis
What is being tested?
GSK2556286
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
92 participants
Where
2 sitesin 2 countries
Study dates
30 Oct 2020to 6 Nov 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 33Show fewer
  • 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:
  • Heart rate of <40 or >100 beats per minute (bpm) in males and <50 or >100 bpm in females.
  • PR interval of <120 or >220 milliseconds (msec) in males and females.
  • QRS duration of <70 or >120 msec in males and females.
  • 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:
  • medical history and examination.
  • 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.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Netherlands1 site

  • GSK Investigational Site

    Groningen, 9713 AG

Other trials in Netherlands

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

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

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.

Conditions
Tuberculosis
Being tested
GSK2556286, Placebo
Keywords
GSK2556286, Pharmacokinetics, Interventional, Tuberculosis, Placebo-controlled, First time in human
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2556286Drug

    GSK2556286 will be administered.

  • PlaceboDrug

    Placebo will be administered

Study groups in NCT04472897
Study groupRoleWhat they receive
Part A: Participants receiving GSK2556286ExperimentalParticipants 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.
Receives: Drug: GSK2556286
Part A: Participants receiving placeboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo
Part B: Participants receiving GSK2556286ExperimentalParticipants 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.
Receives: Drug: GSK2556286
Part B: Participants receiving placeboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs

    Measured: Up to Day 15

  2. Part B: Number of participants with any SAEs and non-SAEs

    Measured: Up to Day 28

  3. Part A: Number of participants with AEs (SAEs and non-SAEs) by severity

    Measured: Up to Day 15

  4. Part B: Number of participants with AEs (SAEs and non-SAEs) by severity

    Measured: Up to Day 28

  5. Part A: Plasma concentrations of GSK2556286

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: Pre-dose on Days 1, 12, 13 and 14

  18. Part B: T1/2 of GSK2556286

    Measured: 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 outcomes (14)

  1. Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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)

    Measured: 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)

    Measured: 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

    Measured: 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)

    Measured: 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

    Measured: 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])

    Measured: 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)

    Measured: 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

    Measured: 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

    Measured: Pre-dose on Days 1, 12, 13 and 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2020
  2. Study start30 Oct 2020
  3. Primary completion6 Nov 2024
  4. Study completion6 Nov 2024

Why it stopped: A decision to stop the study was made by the site and GSK project team based on pre-defined stopping criteria in the protocol

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
This is a double-blind, randomized, sequential, parallel dose cohort study.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04472897
Sponsor's protocol ID
210035
Status last verified
May 2025
First submitted
14 Jul 2020
Last updated
11 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Ilsley E, Banham-Hall E, Chaychenko T, Chinenyeze K, Maher-Edwards G, Muya C, Rolfe K, Sharma R, Tiberi S, Barros-Aguirre D. Randomized, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Oral Doses of Novel Antitubercular Drug Candidate, GSK2556286, in Healthy Adults. J Clin Pharmacol. 2026 May;66(5):e70203. doi: 10.1002/jcph.70203.

    PubMed 42139005

  • Nuermberger EL, Martinez-Martinez MS, Sanz O, Urones B, Esquivias J, Soni H, Tasneen R, Tyagi S, Li SY, Converse PJ, Boshoff HI, Robertson GT, Besra GS, Abrahams KA, Upton AM, Mdluli K, Boyle GW, Turner S, Fotouhi N, Cammack NC, Siles JM, Alonso M, Escribano J, Lelievre J, Rullas-Trincado J, Perez-Herran E, Bates RH, Maher-Edwards G, Barros D, Ballell L, Jimenez E. GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0013222. doi: 10.1128/aac.00132-22. Epub 2022 May 24.

    PubMed 35607978

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2556286 in people with Tuberculosis, run by GlaxoSmithKline at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: A decision to stop the study was made by the site and GSK project team based on pre-defined stopping criteria in the protocol). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs (time frame: Up to Day 15). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04472897, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2025.

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