An AME study of xevinapant in Healthy Male Subjects
Research type
Research Study
Full title
A Phase 1, Open-label, 2-part, Single-dose Study of the Absorption, Metabolism, and Excretion of Oral [14C]-Xevinapant, and Absolute Oral Bioavailability of Xevinapant in Healthy Male Subjects
IRAS ID
291893
Contact name
Samuel Israel
Contact email
Sponsor organisation
Debiopharm International S.A
Eudract number
2021-000301-25
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
IRAS Project ID, 291893; REC Reference , 21/LO/0012
Duration of Study in the UK
0 years, 1 months, 7 days
Research summary
Summary of Research
This study is A Phase 1, Open-label, 2-part, Single-dose Study of the Absorption, Metabolism, and Excretion of Oral [14C]-xevinapant, and Absolute Oral Bioavailability of xevinapant in Healthy Male Subjects.The study drug is currently being developed as a potential cancer treatment.
Subjects will participate in either Part 1 or Part 2 of the study. In both parts, subjects will be screened to assess their eligibility within 28 days prior to dose administration.
Part 1
Subjects will be admitted to the clinic on Day-1 and be confined to the clinic until at least Day 8. On Day 1, subjects will receive a single oral dose of radiolabelled [14C]-xevinapant. Subjects will be discharged once certain radioactivity recovery discharge criteria have been met. If the discharge criteria have not been met by Day 8, subjects will remain in the clinic and excreta samples will continue to be collected until discharge criteria are met, up to Day 15. If the discharge criteria have not been met by Day 15, subjects may be asked to collect excreta samples at home for the 24-hour period prior to additional clinic visits on Days 22 and 29.Part 2
Subjects will be admitted to the clinic on Day-1 and on Day 1 will receive a single oral dose of xevinapant followed 1 hour later by a single radioactive ‘microdose’ of [14C]-xevinapant administered as an intravenous bolus. Subjects will be discharged from the clinic on Day 5.The total study duration is anticipated to be no more than 8 weeks in total in Part 1 or 5 weeks in total in Part 2.
Both parts of the planned study will be conducted at a single research centre (Covance Clinical Research Unit Ltd, Leeds). Six subjects will be enrolled in Part 1 and six subjects will be enrolled in Part 2.
Study drug radioactivity will be in the form of Carbon-14, a naturally occurring radioactive form of carbon. Using radioactivity in this study will allow the study drug and its breakdown products to be measured in the blood, urine, faeces and expired air.Summary of Results
CLINICAL TRIAL RESULTS SUMMARY A 2-part study in healthy men to find out how much of a radioactive oral dose of xevinapant is found in human blood, urine, stool, and breath (Part 1), and how much of an oral dose of xevinapant makes its way into the blood compared to a dose injected directly into a vein (Part 2).
THANK YOU!
Thank you to those who participated in this research study for xevinapant. Without trial participants, drug development would not be possible. Participation in this trial has helped the researchers learn how xevinapant works and how safe it is to use.
The trial information given in this summary is from one trial only and must not be used to make medical decisions. This drug is not yet approved and the outcomes of this trial may not apply to all patients.
WHAT IS XEVINAPANT?
Xevinapant is a blocker of a type of protein that is found to be in excess and overactive in a variety of cancers, including squamous cell carcinoma of the head and neck. This type of protein prevents the body’s immune system from killing cancer cells, and therefore allows cancer cells to survive the effects of chemotherapy and radiotherapy and keep growing. By blocking this protein, doctors hope to use xevinapant in combination with chemotherapy and radiotherapy to treat these types of cancer.
WHAT WAS THE PURPOSE OF THIS CLINICAL TRIAL?
This trial was designed to answer these questions:
Part 1:
How much of a radioactive oral dose of xevinapant is found in urine, stool, and breath?
How much xevinapant and radioactivity is taken up in the blood and how fast?
How much xevinapant and radioactivity goes into the urine and how fast?
How much of the main breakdown product of xevinapant, called D-1143-MET1, is found in the blood and urine, and how quickly does it appear here?
Which compounds are found in the blood, urine, and stool after xevinapant is broken down by the body?
Part 2:
How much of an oral dose of xevinapant makes its way into the blood compared to a dose injected directly into a vein?
HOW WAS THIS TRIAL DONE?
Who took part in this trial?
This trial included 12 healthy men, 6 men in Part 1 and 6 men in Part 2. In Part 1, the men were aged between 35 and 65 years. In Part 2, the men were aged between 18 and 65 years.Where did this trial take place?
This trial took place in the United Kingdom.When did this trial take place?
This trial started in July 2021 and ended in November 2021.What treatments were tested in this trial?
In Part 1, all men who took part in the trial were given 200 mg xevinapant labelled with a radioactive tag ([14C]), to drink as a liquid.
In Part 2, all men who took part in the trial were given 200 mg xevinapant to drink as liquid. One hour later the men were given 100 µg xevinapant labelled with a radioactive tag ([14C]) as an injection into the vein.
The radioactive tag that was used in both parts of this study was an extremely small dose of radioactivity that was known to be well below any harmful limit.What has been completed?
Part 1:
Everyone took their medicine once on the first day of the study and stayed at the study site until Day 8 at the earliest and Day 15 at the latest. How long they stayed at the site depended on whether radioactivity could still be seen in their blood, urine, and stool. Each person on the study collected their urine and stool to give to the study team, and took part in an activity to collect their breath, to see how much of the radioactive label was found. Additionally, blood tests were done to see how much medicine was in the blood. The trial doctor checked for any side effects from the medicine every day the people were at the study site.
Part 2:
Everyone took their medicine on the first day of the study, and was given the injection 1 hour after drinking the liquid. Everyone stayed at the study site until Day 5. Each person on the study collected their urine and stool to give to the study team, to see how much of the radioactive label was found. Additionally, blood tests were done to see how much medicine was in the blood, from both the liquid and the injection.WHAT ARE THE MAIN RESULTS OF THIS TRIAL?
Part 1:
Nearly all (93.5%) of the radioactive-tagged medicine was found in urine and stool. Xevinapant and its breakdown products were removed from the body mostly in the stool (60.2%) and some in the urine (33.3%). None of the radioactivity was found in the breath.
Xevinapant was at its highest level in the blood, half an hour after the medicine was taken. The main breakdown product, called D-1143-MET1, had its highest level in the blood 5 hours after the medicine was taken. Radioactivity was found to be at its highest level in the blood 1 hour after the medicine was taken. Overall, 7 breakdown products were found after testing the blood, urine, and stool samples, with xevinapant found to be mostly broken down into D 1143 MET1.
Part 2:
Overall, about half as much (57.8%) of xevinapant was found in the blood after taking the liquid form of the medicine, compared to the injection (100%).
WHAT WERE THE SIDE EFFECTS?
In this study, some people experienced side effects. Side effects are unwanted medical events (such as a headache) that happen during the study, and are reported because the trial doctor (investigator) thinks the side effects could have been caused by the treatments in the trial. Not all the people in this trial had side effects. None of the men in Part 1 had any side effects.
In Part 2, 2 out of 6 men (33%) had side effects. One man had 2 side effects that were a chest pain not related to the heart, and a reaction where the needle for the injection was placed. Another man had a reaction where the needle for taking blood was placed.
WHAT WAS LEARNED FROM THIS TRIAL?
Findings from this trial will be used to seek approval for using the treatment for people with cancer who are suitable to have this medicine.
WHERE CAN I FIND MORE INFORMATION ABOUT THIS TRIAL?
Trial Title A Phase 1, Open-label, 2-part, Single-dose Study of the Absorption, Metabolism, and Excretion of Oral [14C]-Xevinapant, and Absolute Oral Bioavailability of Xevinapant in Healthy Male SubjectsPublic Trial Title A 2-part study in healthy men to find out how much of a radioactive oral dose of xevinapant is found in human blood, urine, stool, and breath (Part 1), and how much of an oral dose of xevinapant makes its way into the blood compared to a dose injected directly into a vein (Part 2).
Protocol Number Debio 1143-108
EudraCT Number 2021-000301-25
Study Sponsor Debiopharm https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbajv71vHqsNc2VjA316oE9bjimknPNdmhLSAuz-2F2wYMU1HJM_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKWXxhiEAOvGeqwemTru19g8GpL9-2BvDglCJo-2BBrqaTqPtRTG5YG023EuySXyaVSUPL-2FTAwoxZ8u4fJlAucrBOSe1ZQbi8ZBTy6hb6s-2F0bTR3Jafp0jM-2BFlmwQ16QSX7sdhE8f-2FVeBZCFHbEKjy4Z-2FDaV0B3mGGNZTWv4-2FPN7rPl4Q-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cec75ea87f0f34ea900ab08daac765929%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638011921539256841%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Xo1vHY%2BffXA8jwN93HiCWPcI3UQEFw81obr%2Bgvl4cvk%3D&reserved=0
Please email any questions to ClinicalTrials@debiopharm.com This study is also registered on https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cec75ea87f0f34ea900ab08daac765929%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638011921539256841%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=SuVoCI2hIIhxqaMFyY6lZmUKRWirwN752gITzBFII34%3D&reserved=0
ARE THERE PLANS FOR FURTHER TRIALS?
Debiopharm ran other healthy volunteer studies at the same time as this study, and are currently testing xevinapant in clinical trials in patients with cancer. It is hoped that clinical trials with xevinapant will show that this is a safe and effective medication that can be used in the future.REC name
London - Brent Research Ethics Committee
REC reference
21/LO/0066
Date of REC Opinion
13 May 2021
REC opinion
Further Information Favourable Opinion