Safety, tolerability and pharmacokinetics investigation of GSK3494245
Research type
Research Study
Full title
A randomized, double-blind, placebo-controlled, first time in human study to evaluate the safety, tolerability and pharmacokinetics of single (in both fed and fasted states) doses of GSK3494245 in healthy participants
IRAS ID
276086
Contact name
Deborah Wong
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2019-004492-39
Duration of Study in the UK
0 years, 8 months, 14 days
Research summary
Research Summary
GlaxoSmithKline (GSK) is developing a new medicine (GSK3494245) 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. Our study drug works by disrupting the process the parasites use to recycle and remove unwanted proteins, which leads to the death of the parasite. If the study drug works, it will provide a better treatment option for patients with VL.
This is the first time GSK3494245 will be studied in humans. The main objective of the study is to test the safety, tolerability and blood levels of single doses of GSK3494245 when given as oral capsules in healthy volunteers. The study will also investigate the effect of food intake on the amount of GSK3494245 that enters the blood. The results will be used to decide the appropriate doses of GSK3494245 to be used in further studies.
The study will include approximately 30 healthy male participants. They will be randomly allocated to receive an oral dose of either GSK3494245 or placebo.
The study will consist of 3 Cohorts:
o Cohorts 1 and 2 (8 participants each). Each participant will receive either a single dose of GSK3494245 or placebo at 4 different in-patient visits.
o Cohort 3 (14 participants). Each participant will receive a single dose of GSK3494245 at 2 different inpatient visits (one dose given in a fasted state and another in a fed state).Study participants will stay in the clinical unit for a period of 5 days (4 overnight stays) after each dosing, during which observation and assessments will be carried out.
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.
Lay summary of study results
This study was planned to include two parts. Participants received either a dose of the study medicine, GSK3294245, or placebo (this is a tablet with no active ingredients, like a sugar pill).
Part A Single Ascending Dose (SAD): This part involved testing increasing doses of GSK3494245 starting with lower doses and moving to higher ones. There were up to three groups in this part.
• Group 1: Participants received two increasing doses of GSK3494245 and one dose of a placebo without food.
• Group 2: Participants received four increasing doses of GSK3494245 and one dose of a placebo without food. Group 2A tested one additional dose of GSK3494245 and placebo in participants without food.
• Group 3: This group tested how food affected GSK3494245. Participants received a single dose of GSK3494245 and placebo both with and without food. After Group 3 was completed, Group 3A tested two increasing doses of GSK3494245 with food.
Part B Multiple Ascending Dose (MAD): This part was planned to test repeat doses of GSK3494245 given twice daily for seven days. This part was not started as the study team decided to stop the study.
This was a double-blind study. A double-blind study means that neither the participants nor the study doctor/researchers knew which treatment (medicine or placebo) the participants received. The study doctor and researchers only knew whether the participant received a dose of GSK3494245 or placebo at the end of the study.
The safety of all participants was monitored throughout the study. Participants were also followed up between 7 to 14 days after receiving the last dose of the study treatment in each group.
The study took longer to complete than expected. This was due to the coronavirus disease 2019 (COVID-19) pandemic and lockdowns in the United Kingdom. Additional time was also needed to carefully review the data and make adjustments in the dosages of the study medicine in each group.
After looking at the results of the participants in Group 3A, the sponsor decided to stop the study. This decision was not due to any safety concerns, but because it appeared unlikely that the study medicine could be given once or twice a day without food, as required for effective treatment of the disease.
Researchers found that GSK3494245 was found to be acceptable to participants when taken with food and without food. No significant side effects were found that were related to the study medicine. Although this study medicine will not be studied further, the information from this study may help other researchers develop new medicines for Visceral leishmaniasis or other parasitic diseases.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
20/EE/0184
Date of REC Opinion
30 Jul 2020
REC opinion
Favourable Opinion