210035 FTiH study for safety, tolerability, and PK of GSK2556286
Research type
Research Study
Full title
A randomised, double-blind, 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.
IRAS ID
308526
Contact name
Edward Banham-Hall
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2019-004420-38
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 5 months, 7 days
Research summary
Summary of Research
GlaxoSmithKline (GSK) is developing a new drug (GSK2556286) for the treatment of Tuberculosis. Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). TB was the top infectious disease killer worldwide accounting for more than 10 million cases and 1.5 million deaths in 2018.
Currently, the successful treatment of TB with combination drug regimens is hindered by long treatment durations, drug resistance, poor tolerability and lack of adherence. New safe and effective medicines with novel mechanisms of action are required.
GSK2556286 demonstrated activity against drug sensitive and drug resistant Mtb strains and did not demonstrate cross-resistance to other TB drugs. In animal studies, GSK2556286 has been shown to have good penetration into granulomas, which is a hallmark of TB disease, and demonstrated treatment-shortening potential. If the study drug works, it may be a good partner drug for future anti-TB combination regimens, with the potential to shorten the duration of treatment for TB.
This is the first time GSK2556286 will be studied in humans. The main objective is to test the safety and tolerability of single and repeat doses of orally administered GSK2556286 in healthy participants, and to measure concentrations of drug in the blood at various time intervals (pharmacokinetics).
Approximately 120 male and female (of non-childbearing potential) participants will be enrolled in the study, which consists of 2 parts:
- Part A (single dose) will consist of 88 participants (11 cohorts of 8).
- Part B (repeat dose) will consist of 32 participants (4 cohorts of 8).In each part, participants will be allocated randomly to receive a dose of either GSK2556286 or placebo.
Participation has no direct benefit to participants. This study is sponsored by GSK and will be conducted in a Medicines and Health Care Products Regulatory Agency (MHRA) accredited clinical research unit in the United Kingdom.
Summary of Results
A total of 92 participants from 2 countries, Netherlands and the United Kingdom took part in this study. The details of the participants were as follows. This was a ‘double-blind’ study, meaning, neither the study doctor nor the participants knew which study treatment the participant received. The study had two parts: Part A and Part B as shown in the study design figure.Part A: In this part, researchers tested single, increasing dose of GSK2556286 in 10 groups of participants. In each group, up to 6 participants received GSK2556286, while 2 received placebo. A placebo is a dummy medicine without any active ingredient. It is used in research studies to compare how well a new medicine works compared to the placebo. GSK2556286 and placebo were given as oral tablets. To see the effect of food, initially, GSK2556286 was given in a fasted state (on an empty stomach). Some groups explored the effects of taking the medicine after eating a high-fat meal to see how food impacted the medicine’s safety, tolerability, and behaviour in the body. This food-effect group was studied at the same time as the groups testing increasing doses of the medicine. Results from Part A informed the meal type in Part B.
Part B: Here, researchers tested multiple increasing doses of GSK2556286 when given daily for 14 days in 2 groups. In each group, approximately 6 participants received GSK2556286 and 2 received a placebo. Appropriate doses for Part B were selected by the dose escalation committee based on findings from Part A or previous doses in Part B. It was planned to include 4 groups in Part B, however, after reviewing the results from Group 2B (650 milligrams [mg]), the researchers decided to stop the study early and did not continue with the remaining groups.
There were no serious side effects related to the study medicines and no deaths were reported in this study.
In Part A, non-serious side effects related to the study medicines were reported by 1 participant (17%) in Group 1A and Group 2A, 1 participant (33%) in Group 3A, and 2 participants (40%) in Group 10A. Participants in the placebo group and other groups of Part A did not report any non-serious side effects. The below table shows the non-serious side effects reported by the participants.
In Part B, non-serious side effects related to the study medicines were reported by 2 participants (29%) in Group 1B, 4 participants (67%) in Group 2B, and 1 participant (25%) in the placebo group.
After carefully examining the safety results and how GSK2556286 behaved in the body, the study was concluded in November 2024. Due to significant differences in how GSK2556286 was absorbed and processed in the body of the participants, as well as frequent headaches being reported by some subjects in part B, GSK, the sponsor of this study, decided to stop development of GSK2256286.
After this phase of the study completed, GSK2556286 was tested with healthy volunteers receiving the medication daily for several days. During this part of the study a greater number of healthy volunteers reported headaches than would be expected. The healthy volunteers remained safe and well otherwise, with normal investigations. Their headaches resolved fully when they stopped taking GSK2556286. However, the decision was taken to stop the study and not develop GSK2556286 further.
REC name
HSC REC A
REC reference
21/NI/0185
Date of REC Opinion
3 Dec 2021
REC opinion
Favourable Opinion