Absorption and elimination of radiolabelled GSK3640254 Version 1
Research type
Research Study
Full title
A two-period study in healthy male participants to determine the pharmacokinetics, balance/excretion, and metabolism of [14C]-GSK3640254 following a single intravenous radiolabeled microtracer dose (concomitant with a non-radiolabeled oral dose) and a single oral radiolabeled dose. (HMR code: 19-015)
IRAS ID
280687
Contact name
Temitope Adeloye
Contact email
Sponsor organisation
ViiV Healthcare
Eudract number
2019-004444-30
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
The study medicine is an experimental treatment for HIV-1 infection. HIV-1 is a virus that infects and damages cells in the immune system, weakening the body’s ability to fight infections and disease. If people with HIV-1 aren’t treated, they can develop AIDS, which is life threatening. There’s no cure for HIV-1, but it can be treated with existing medicines (called ‘antiretrovirals’) that stop the virus from replicating in the body. The study medicine is a new type of antiretroviral medicine. We hope it will give patients infected with HIV-1 more treatment options.The study medicine has already been tested in healthy people and people who have HIV-1. We’re doing this study in healthy men to find out how much of the study medicine gets into the blood, and how the body breaks it down and gets rid of it. To do that, we’ll ‘label’ the study medicine with a small amount of radioactivity, called carbon-14. We’ll measure the label to detect traces of the study medicine, and its breakdown products, in blood, urine, faeces (‘poo’), and bile. We’ll also check for side effects.
We’ll enrol 6 healthy men, aged 30–50 years. They’ll have 2 study sessions. In Session 1, they’ll receive a dose of study medicine by mouth, as 2 tablets, and a tiny ‘microdose’ by slow injection into a vein. In Session 2, they’ll receive a dose of study medicine by mouth, as a liquid.
Participants will take up to 5½ weeks to finish the study. They’ll stay on the ward for 16 nights (8 nights in each session) and make 2 outpatient visits. Participants may stay on the ward for longer in Session 2, depending on the results.
A pharmaceutical company ViiV Healthcare is funding the study.
The study will take place at 1 centre in London.
Summary of Results
Researchers look at the results of many studies to understand if experimental new medicines work and how they work. It takes lots of people in many studies all around the world to advance medical science. This summary shows the results from only this study. Other studies may find different results.We are extremely grateful to the study participants who took part in this important research.
Why did we do the study?
The study medicine (GSK3640254) is an experimental new treatment for human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 is a virus that infects and damages cells in the immune system, weakening the body’s ability to fight infection and disease. If people with HIV-1 aren’t treated, they can develop AIDS, which is life threatening. There’s no cure for HIV-1, but it can be treated with existing medicines (called ‘antiretrovirals’) that stop the virus from replicating in the body. The study medicine is a new type of antiretroviral medicine. We hope it will give patients infected with HIV-1 more treatment options.In this study we tested single doses of the study medicine in healthy volunteers, to find out how much of it gets into the bloodstream, and how the body breaks it down and gets rid of it. To do that, we ‘labelled’ the study medicine with a small amount of radioactivity, called carbon-14. We measured the label to detect traces of the study medicine and its breakdown products, in blood, urine, faeces (‘poo’) and bile. We also checked for side effects.
Who organised the study and when did it take place?
This study was paid for by ViiV Healthcare – a company that develops drugs and advances in the treatment and care of people with HIV. GlaxoSmithKline (also called “GSK”) – a company that discovers and makes vaccines, medicines and other health products – was responsible for running the study for ViiV Healthcare. ViiV Healthcare – through GSK – paid HMR to run this study.The doctors and support staff of HMR, London organised the study. The doctors at HMR have no financial interest in ViiV Healthcare or GSK.
The study took place at HMR (London) from 24 September 2020 until 23 November 2020. We completed the study as planned.
Who took part in the study and what treatments did they take?
5 healthy men, aged 31–45 years, took part in the study. They had 2 study sessions. In Session 1, they received a single dose of 200 mg study medicine by mouth, as 2 tablets, and a tiny ‘microdose’ of 100 micrograms study medicine by slow injection into a vein over 1 h. In Session 2, they received a single dose of 85 mg study medicine by mouth, as a liquid.The doses of study medicine that participants received by slow injection into a vein, and by mouth as a liquid, were ‘labelled’ with a small amount of radioactivity, called carbon-14. The amount of radiation participants were exposed to was about a third (0.93 milliSieverts) of the total amount of background radiation (2.7 milliSieverts) that the average UK resident is exposed to each year.
What were the results of the study?
Side effects
Side effects are unwanted medical events (such as headache) that happen during the study and are reported because the study doctor believes the side effects may have been related to the study medicine. In this study, we found out the following.
• There were no serious side effects – those are side effect that are life threatening or required someone to go to hospital.
• Only 1 out of 5 people (20%) had side effects. That person reported a feeling of weakness or a lack of energy after taking the study medicine in both study sessions, and feeling sick after taking the study medicine as a liquid (by mouth) in Session 2.Other results
We found out how much of the study medicine gets into the bloodstream, and how the body breaks it down and gets rid of it, as follows.
• The body got rid of the study medicine within about 7 days after each dose.
• By labelling the study medicine, we were able to find out how the body gets rid of (‘excretes’) the study medicine. The results showed that most of the study medicine was excreted in the faeces (97.5%). A small amount of study medicine was excreted in the urine (2.5%). Only small amounts of the study medicine are broken down in the gut and liver.
• When the study medicine was taken by mouth, about ⅕ of the dose got into the bloodstream (21.4%). The amount of the study medicine dose that got into the bloodstream was slightly higher when it was given as a liquid compared with when it was given as tablets.
The study medicine was well tolerated at the doses and duration tested.How has the study helped patients and researchers?
The results of this study will be used to decide the doses of study medicine to be tested in future studies in patients with HIV-1 infection, so we can find out if patients are helped by the study medicine.Are there plans for further studies?
Studies of GSK3640254 (the study medicine) are ongoing and further trials are planned in patients with HIV-1 infection.Where can I find more information about the study?
You can find out more detailed information about this study at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C3281f9688b50443f1e4908d9e4dc7fc9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792458535606467%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=%2BVcV5ARY71WrjC9eMa7IWskMVUpc7ADmDSbiPRLcEIY%3D&reserved=0 and on the ViiV Study Register (https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.viiv-studyregister.com%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C3281f9688b50443f1e4908d9e4dc7fc9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792458535606467%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=lcxqM%2B9awBRmbqtv6IYtAchONv4Cea8BiOBK1QSmHwA%3D&reserved=0).If you would like more general information about clinical trials, the UK Clinical Research Collaboration (UKCRC) booklet ‘Understanding Clinical Trials’ has information about medical research, and questions you might want to ask. If you’d like to read it, please visit https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.ukcrc.org%2Fwp-content%2Fuploads%2F2014%2F03%2FiCT_Booklet.pdf&data=04%7C01%7Capprovals%40hra.nhs.uk%7C3281f9688b50443f1e4908d9e4dc7fc9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792458535606467%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=QJ6z4qvzlP9s03Unf2gd9zO4AFUrE30qBPjT%2FWdlscg%3D&reserved=0.
REC name
London - Brent Research Ethics Committee
REC reference
20/LO/0806
Date of REC Opinion
3 Sep 2020
REC opinion
Further Information Favourable Opinion