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

Completed

Conditions: Tuberculosis
10028440

Registration Number: NL-OMON55164

Lead Sponsor: GlaxoSmithKline

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 96

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 an EMA-approved COVID-19 vaccine 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 in consultation with the Medical
Monitor (if required) agree and document that the finding is unlikely to
introduce additional risk factors and will not interfere with the study
procedures.
Note: Screened participants with laboratory values outside of the normal range
may be rescreened once for inclusion into the study at the discretion of the
Investigator.
Body weight *50kg, and body mass index (BMI) within the range 19 to 29.9 kg/m2
inclusive.
Male and/or Female Participants:
Male participants:
A male participant with a female partner of reproductive potential must agree
to use contraception as detailed in Appendix 4 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.
Female participants:
A female participant is eligible to participate if she is not a woman of
childbearing potential (WONCBP) as defined in Appendix 4 of this clinical study
protocol.
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, haematological,
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) >1.5xupper limit of normal (ULN)
Total bilirubin >1.5xULN (isolated total bilirubin >1.5xULN may be acceptable,
after consultation with the GSK Medical Monitor, if total bilirubin is
fractionated and direct bilirubin <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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability of GSK2556286:<br /><br>Number and severity of Serious and Non-Serious Adverse Events.<br /><br><br /><br>Plasma concentrations of GSK2556286 plus derived parameters, as data allow.<br /><br>For Single Ascending Dose (SAD) part: Derived pharmacokinetic parameters for<br /><br>GSK2556286 including area under the plasma drug concentration versus time curve<br /><br>(AUC(0-t), AUC(0-), maximum observed plasma drug concentration (Cmax), time to<br /><br>maximum observed plasma drug concentration (tmax) and apparent terminal<br /><br>half-life (t1/2) as data allow.<br /><br>For Multiple Ascending Dose (MAD) part: AUC(0-t), AUC(0-), AUC(0-), Cmax,<br /><br>tmax, trough plasma concentration (C) and t1/2.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>For SAD part: Derived pharmacokinetic parameters for GSK2556286 following<br /><br>single dose (fasted and fed) including area under the plasma drug concentration<br /><br>versus time curve (AUC(0-t), AUC(0-), Cmax, tmax, t1/2 as data allow.<br /><br>Dose-proportionality assessment using derived PK parameters, as data allow:<br /><br>For SAD part: AUC(0-), AUC(0-t), Cmax<br /><br>For MAD part: AUC(0-), Cmax<br /><br>Observed accumulation ratio based on AUC (Ro) and Cmax (RCmax) and steady-state<br /><br>ratio (Rss) following repeat dosing.<br /><br>Trough plasma concentrations at the end of the dosing interval (C) to assess<br /><br>the achievement of steady-state of GSK2556286 following repeat oral doses.</p><br>