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

NCT04472897 | Terminated Phase 1 DMC

• 1 other identifier: 210035
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 2

Brief 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. The findings will help determine appropriate dosing for future clinical studies.

Conditions

Tuberculosis

Keywords

GSK2556286; Pharmacokinetics; Interventional; Tuberculosis; Placebo-controlled; First time in human

Outcome Measures

Primary Outcomes (18)

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

  Up to Day 15

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

  Up to Day 28

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

  Up to Day 15

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

  Up to Day 28

• Part A: Plasma concentrations of GSK2556286

  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

• 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

  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

• Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286

  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

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

  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

• Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286

  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

• Part A: Apparent terminal half-life (T1/2) of GSK2556286

  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

• Part B: Plasma concentrations of GSK2556286

  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

• Part B: AUC(0-t) of GSK2556286

  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

• Part B: AUC(0-inf) of GSK2556286

  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

• 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

  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

• Part B: Cmax of GSK2556286

  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

• Part B: Tmax of GSK2556286

  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

• Part B: Trough plasma concentration (Ctau) of GSK2556286

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

• Part B: T1/2 of GSK2556286

  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)

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

  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

• Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions

  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

• Part A: Cmax of GSK2556286 under fasted and fed conditions

  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

• Part A: Tmax of GSK2556286 under fasted and fed conditions

  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

• Part A: T1/2 of GSK2556286 under fasted and fed conditions

  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

Study Arms (4)

Part A: Participants receiving GSK2556286

EXPERIMENTAL

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

Part A: Participants receiving placebo

PLACEBO COMPARATOR

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

Part B: Participants receiving GSK2556286

EXPERIMENTAL

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

Part B: Participants receiving placebo

PLACEBO COMPARATOR

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

Interventions

GSK2556286 DRUG

GSK2556286 will be administered.

Part A: Participants receiving GSK2556286; Part B: Participants receiving GSK2556286

Placebo DRUG

Placebo will be administered

Part A: Participants receiving placebo; Part B: Participants receiving placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Groningen, 9713 AG, Netherlands

Location

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35607978 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a double-blind, randomized, sequential, parallel dose cohort study.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 16, 2020
• Study Start: October 30, 2020
• Primary Completion: November 6, 2024
• Study Completion: November 6, 2024
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

GB (1); NL (1)