GSK3186899 First Time in Human Study
Research type
Research Study
Full title
A randomized, double-blind (sponsor unblinded), placebo-controlled, first time in human study to evaluate the safety, tolerability and pharmacokinetics of single (in both fed and fasted states) and repeat doses of GSK3186899 in healthy participants
IRAS ID
254459
Contact name
Disala Fernando
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2018-004642-42
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 2 months, 14 days
Research summary
Research Summary
GlaxoSmithKline (GSK) is developing a new medicine (GSK3186899) for the treatment of an infectious disease called visceral leishmaniasis (VL). The disease is caused by a parasite and can lead to death if left untreated. GSK3186899 works by inhibiting a complex of two parasite proteins, believed to be involved in the cell cycle process, that leads to the death of the parasite.
This is the first time GSK3186899 will be studied in humans. The main objective of the study is to test the safety, tolerability and blood levels of GSK3186899. The results will be used to determine the appropriate doses of GSK3186899 to be used in further studies. The study will also investigate the effect of food on the absorption of GSK3186899 (Group 3).
The study will include approximately 54 healthy participants, including males, and females who are unable to have children. They will be randomly allocated to receive an oral suspension of either GSK3186899 or placebo.
The study will consist of 2 parts:
• Part A: 30 participants divided into 3 groups:
o Groups 1 and 2 (8 participants each). Each participant will receive either a dose of GSK3186899 or placebo at 4 different in-patient visits.
o Group 3 (14 participants). Each participant will receive either a dose of GSK3186899 or placebo at 2 different in-patient visits (one dose given in a fasted state and another in a fed state).
• Part B: 24 participants in 3 groups of eight. Each participant will receive twice daily doses of GSK3186899 or placebo for 10 days.Taking part in the study will not have a direct benefit to volunteers. The 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, with adequate safety and compliance facilities.
Summary of Results
A total of 25 male participants were enrolled for the study. The average age of the population was 38 years (range: 20-51 years). A majority (79%) of the participants were of White/Caucasian or European heritage.
GSK3186899 was rapidly absorbed following single dose administration of 30 mg to 800 mg. The time taken for the drug concentration to become half of the original concentration was approximately 2 to 5 hours for the 30 mg to 800 mg dose range. Increasing single doses from 30mg to 800mg showed both the maximum observed concentration of the drug and the total exposure of the drug experienced by the subjects increased in a greater than predicted manner.
A total of 12 participants in the study experienced at least 1 side effect in Part A. One participant discontinued study treatment due to abdominal discomfort, which was assessed was of mild severity and not considered related to the study treatment by the investigator. No serious side effects or any other significant side effects were reported during the study.
There were no clinically significant changes in the subjects’ blood and urine tests during the study.
Clinically significant findings were observed during heart rhythm monitoring for 2 participants. One participant underwent a Magnetic Resonance Imaging (MRI) procedure which confirmed the normal heart function of the volunteer and the normal appearance of his heart chambers. No further investigation or active treatment was deemed necessary for this participant. The other participant had isolated episodes of arrhythmia (changes in heart rhythm) which was not causing any symptoms. No further arrhythmia was detected with extended heart monitoring and no further investigation was required at that point. This was judged by the investigator as unrelated to the study medication as the participant has had similar abnormalities prior to dosing on heart rhythm monitoring. One participant experienced a drop in his blood pressure, but this was assessed as not clinically significant since the volunteer already had low blood pressure prior to dosing.
REC name
HSC REC B
REC reference
19/NI/0039
Date of REC Opinion
3 Apr 2019
REC opinion
Further Information Favourable Opinion