Safety and pharmacokinetics of NTP42:KVA4
Research type
Research Study
Full title
A Phase I trial to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending doses of NTP42:KVA4 in healthy volunteers.
IRAS ID
295192
Contact name
Therese Kinsella
Contact email
Sponsor organisation
ATXA Therapeutics Limited
Eudract number
2020-005972-37
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Summary of Research
NTP42:KVA4 is a new experimental medicine for treating pulmonary arterial hypertension (PAH). PAH is characterized by high blood pressure in blood vessels that carry blood from the heart to the lungs. The high blood pressure causes these vessels to become stiff, thickened and inflamed which makes it harder for the heart to pump blood through them. People with PAH experience several symptoms including shortness of breath, tiredness, dizziness, palpitations (awareness of heartbeat), and chest pain. While there are treatments to improve the symptoms of PAH, there’s currently no cure. We hope that NTP42:KVA4 will treat PAH by blocking a substance that causes the symptoms in the lungs and heart.We’re doing this study to find out the side effects and blood levels of single and repeated doses of NTP42:KVA4, and to also find out if food affects the absorption of NTP42:KVA4 into the bloodstream. NTP42:KVA4 has never been given to humans before, so we’ll start with a small dose and gradually increase the dose as the study progresses.
The study, carried out in healthy men aged 18–55, has 3 parts (A, B and C).
In Part A, 7 groups of up to 8 participants will either receive single doses of NTP42:KVA4, or placebo, by mouth. In Part B, one of the groups who participated in Part A will return for a second session, where they’ll receive a single dose of NTP42:KVA4 after a high-fat breakfast. In Part C, 3 groups of up to 8 participants will receive repeated doses of NTP42:KVA4 , or placebo, for 7 days. Participants will stay on the ward for up to 10 days and will return for a final follow-up visit 7-10 days later.
A pharmaceutical company (ATXA Therapeutics Ltd) is funding the study.
The study will take place at 1 centre in London.
Summary of Results
ATXA Therapeutics Limited wish to thank the volunteers who participated in the Phase I trial to evaluate the safety and pharmacokinetics of their drug NTP42, taken as the experimental medicine NTP42:KVA4.Study Title: A Phase I trial to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending doses of NTP42:KVA4 in healthy volunteers.
Trial Sponsor: ATXA Therapeutics Limited Trial Site: Hammersmith Medicines Research (HMR), London, United Kingdom Trial Period: 17th May 2021 to 20th January 2022
Trials Details:
EudraCT Number: 2020-005972-37
ClinicalTrials.gov Identifier: NCT04919863Neither the study drug NTP42, nor in its form as an experimental medicine NTP42:KVA4, have been evaluated in humans prior to this Phase I clinical trial in healthy volunteer men.
The Phase I trial consisted of three parts:
Part A: Seven groups of healthy volunteers were given single oral doses of NTP42:KVA4 or placebo, where doses were escalated from 0.25 mg to 243 mg NTP42:KVA4 between groups. Volunteers had fasted (no food or drink other than water) overnight prior to taking the test drug or placebo.
Part B: One dose group from Part A took a second drug dose (9 mg NTP42:KVA4 or placebo) after eating a high-fat breakfast.
Part C: Three groups of healthy volunteers were given repeated, once daily oral doses of NTP42:KVA4 (either 15 mg, 45 mg or 135 mg) or placebo for 7 days. Volunteers had fasted before taking each dose.A total of 79 healthy male volunteers, aged between 18 and 55 years, were enrolled in the trial.
Safety Results: Of the 79 volunteers enrolled in the trial, 57 received at least 1 dose of NTP42:KVA4. Overall, NTP42:KVA4 was well tolerated at all doses tested during the trial and when taken with or without food. There were no deaths, non-fatal serious AEs (SAEs), other significant AEs, or AEs leading to volunteer withdrawal from treatment. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity; there were no severe TEAEs.
There was no apparent relationship between the dose of NTP42:KVA4 and overall incidence of TEAEs in any part of the trial.
There were no changes in laboratory tests (blood or urine measurements), blood pressure and heart rate, rhythm or activity in volunteers receiving single or repeat doses of NTP42:KVA4.
Pharmacokinetics & Pharmacodynamics:
The pharmacokinetic data (effect of the body on the drug) showed that the blood levels of NTP42 increased as the NTP42:KVA4 dose increased, and the trial determined that the experimental medicine can be taken once daily either with or without food. The pharmacodynamic data (effect of the drug on the body) showed that blood levels of the drug matched the predicted biologic effects on the body.Other Information:
Following the successful completion of the Phase I trial and confirmation that it is a safe and well-tolerated drug, further clinical studies in patients are planned for NTP42:KVA4.Further information about the trial may be found at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMk1YwgzxDHQc9QhbqTFJ8Ew-3D-3DAWwo_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKNsJEC0fX4Kt0qER9rdtzngs8XNiwj8kAYVqMNhMcrzJHol5OWOh8JJm3egyegmF5n2OmrzTCFgKMUtkxxjHFtsnY7hyggfS5FFPkVukwTd3HKWohhUazcBx-2BaXVtlzzC5IQj6Q3tYpt8DFgYe3ZN4jlvLUCEhVpDMd0aMmBe-2B4Q-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cc8d0b7f3d82c4f581ccc08da79481ff6%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637955647924565428%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ubwvN9U2U%2BvH%2B6eyRlOUB%2BKQAmoSWykUMe6KT0iRIo8%3D&reserved=0 Additional information about the study drug NTP42 or its experimental medicine NTP42:KVA4 may be found at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.atxatherapeutics.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cc8d0b7f3d82c4f581ccc08da79481ff6%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637955647924565428%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=RI1NAWsKB96HVANsFS7TSlElTR2d3jDGE%2BEmJsN%2Bj%2Bg%3D&reserved=0.
REC name
North East - York Research Ethics Committee
REC reference
21/NE/0069
Date of REC Opinion
28 Apr 2021
REC opinion
Further Information Favourable Opinion