Tuberculosis
Conditions
Keywords
GSK2556286, Pharmacokinetics, Interventional, Tuberculosis, Placebo-controlled, First time in human
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.
Interventions
DRUGGSK2556286
GSK2556286 will be administered.
DRUGPlacebo
Placebo will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study.
Intervention model description
This is a double-blind, randomized, sequential, parallel dose cohort study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Part A: Dose proportionality of GSK2556286 based on AUC(0-inf) | 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: Dose proportionality of GSK2556286 based on AUC(0-t) | 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: Dose proportionality of GSK2556286 based on Cmax | 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: Dose proportionality of GSK2556286 based on AUC(0-tau) | 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: Dose proportionality of GSK2556286 based on Cmax | 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: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro]) | 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: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax) | 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: Steady state ratio (Rss) 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: Ctau at the end of the dosing interval to assess steady state of GSK2556286 | Pre-dose on Days 1, 12, 13 and 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 |
Countries
Netherlands, United Kingdom
Outcome results
None listed