To investigate the safety and tolerability of GSK2556286 after single ascending and repeat oral doses in healthy adult participants.To determine the pharmacokinetics of single and repeat oral doses of GSK2556286 in healthy participants.To assess the…
ID
Source
Brief title
Condition
- Mycobacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability of GSK2556286:
Number and severity of Serious and Non-Serious Adverse Events.
Plasma concentrations of GSK2556286 plus derived parameters, as data allow.
For Single Ascending Dose (SAD) part: Derived pharmacokinetic parameters for
GSK2556286 including area under the plasma drug concentration versus time curve
(AUC(0-t), AUC(0-*), maximum observed plasma drug concentration (Cmax), time to
maximum observed plasma drug concentration (tmax) and apparent terminal
half-life (t1/2) as data allow.
For Multiple Ascending Dose (MAD) part: AUC(0-t), AUC(0-*), AUC(0-*), Cmax,
tmax, trough plasma concentration (C*) and t1/2.
Secondary outcome
For SAD part: Derived pharmacokinetic parameters for GSK2556286 following
single dose (fasted and fed) including area under the plasma drug concentration
versus time curve (AUC(0-t), AUC(0-*), Cmax, tmax, t1/2 as data allow.
Dose-proportionality assessment using derived PK parameters, as data allow:
For SAD part: AUC(0-*), AUC(0-t), Cmax
For MAD part: AUC(0-*), Cmax
Observed accumulation ratio based on AUC (Ro) and Cmax (RCmax) and steady-state
ratio (Rss) following repeat dosing.
Trough plasma concentrations at the end of the dosing interval (C*) to assess
the achievement of steady-state of GSK2556286 following repeat oral doses.
Background summary
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis
(Mtb). According to the WHO 2019 report it was the top infectious disease
killer worldwide accounting for more than 10 million cases and 1.5 million
deaths in 2018.
The study will evaluate the safety, tolerability and pharmacokinetics (PK)
profile of single and repeat ascending doses of GSK2556286. A food effect (FE)
cohort will investigate the influence of food on the PK of GSK2556286. Results
of this study are intended to be used to identify doses of GSK2556286 to be
used in further studies. This study will be conducted at a single centre.
Study objective
To investigate the safety and tolerability of GSK2556286 after single ascending
and repeat oral doses in healthy adult participants.
To determine the pharmacokinetics of single and repeat oral doses of GSK2556286
in healthy participants.
To assess the effect of food on the pharmacokinetics of GSK2556286 following an
oral dose in healthy participants.
To assess preliminary dose proportionality of GSK2556286 following single and
repeat oral doses.
To examine the extent of accumulation and achievement of steady-state following
repeat oral doses of GSK2556286.
Study design
The study is a randomised, double blind (sponsor unblinded), placebo-controlled
study. Inclusion of the placebo arm will allow for an evaluation of adverse
events attributable to treatment versus those independent of treatment. There
are two parts to the study:
Part A will be a single-ascending dose, sequential, parallel cohort design
including up to 8 cohorts. Each dosing cohort will comprise of 8 participants
(6 active: 2 placebo) dosed under fasted conditions. Each participant will only
participate in one cohort, where they will be randomised to receive a single
dose of either GSK2556286 or matching placebo, administered in a 3:1 ratio
according to the randomisation schedule in a blinded manner. Sentinel dosing
will be used in each cohort. One cohort will investigate the effect of food
administration (high fat meal) on safety, tolerability and PK after a single
dose of GSK2556286. Based on emerging data, a second food effect cohort may
also be included using a higher dose of GSK2556286.
The food effect cohorts may be dosed in parallel with the ascending dose
cohorts, based on review of safety and PK data of the fasted cohorts by the
Dose Escalation Committee (Section 5.4.2).
Part B will be a multiple-ascending, sequential, parallel dose cohort design
including up to 4 cohorts. Each cohort will comprise of 8 participants (6
active: 2 placebo). Each participant will only participate in one cohort, where
they will be randomised to receive a daily dose of GSK2556286 or matching
placebo over a period of up to 14 days, administered in a 3:1 ratio according
to the randomisation schedule in a blinded manner. Sentinel dosing will be used
in each cohort. Part B may include drug administration after either fed or
fasted conditions, dependent on the results from Part A.
Intervention
GSK2556286 Tablets for oral administration are available as white tablets
containing 25 mg, 75 mg, or 250 mg of the drug substance GSK2556286A (free
base).
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the protocol for further
information.
Stockley Park West, 1-3 Ironbridge Road Uxbridge
Middlesex UB11 1BT
GB
Stockley Park West, 1-3 Ironbridge Road Uxbridge
Middlesex UB11 1BT
GB
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004420-38-NL |
| CCMO | NL74338.056.20 |