Safety, pharmacokinetics (PK) and relative bioavailability of NTP42:KVA4 oral formulations
Research type
Research Study
Full title
A Phase 1, randomised, open-label, 3-way crossover study to evaluate the safety, tolerability, pharmacokinetics (including food effect), and relative bioavailability of NTP42:KVA4 administered as a drug-in-capsule, compared with an oral suspension, in healthy volunteers
IRAS ID
1008376
Contact name
Therese Kinsella
Contact email
Sponsor organisation
ATXA Therapeutics Limited
Clinicaltrials.gov Identifier
Research summary
Research Summary
NTP42:KVA4 (the study medicine) is an experimental new medicine for treating pulmonary arterial hypertension (PAH) – high blood pressure in the vessels that carry blood from the heart to the lungs.
In people with PAH, the walls of these blood vessels become stiff and thickened, so blood flows through them more slowly. This makes it harder for the heart to pump blood so the blood pressure inside the vessels increases. Over time this can cause serious damage to the heart, which can lead to death. People with PAH may suffer a wide range of symptoms, including shortness of breath, tiredness, dizziness, palpitations (awareness of heartbeat), swelling in the legs and feet, and chest pain.
Current treatments for PAH improve symptoms but do not treat the cause of the disease – the changes to the blood vessels that carry blood from the heart to the lungs. We hope that the study medicine will work by blocking a substance that causes these changes.
In previous studies in healthy volunteers, NTP42:KVA4 was taken in liquid form. But it would be more convenient for patients to take it as capsules. We’ll test single doses of the study medicine in up to 12 healthy volunteers (aged 18–55) to compare 2 forms of the study medicine: an existing liquid form and a new capsule form.
We aim to find out the side effects and blood levels of the study medicine, how similar the liquid and capsule forms are, and if food affects how much study medicine gets into the bloodstream when given as a capsule.
Participants will have 3 study sessions, and take up to 4 weeks to finish the study. First, they’ll have a screening visit. In each study session, they’ll stay on the ward for 2 nights in a row and make 2 outpatient visits. Then they’ll have a final follow-up visit about a week after their last dose.
A pharmaceutical company ATXA Therapeutics Limited is funding the study.
The study will take place at 1 centre in London.
Summary of Results
"The Trial consisted of three sessions. In each session, volunteers received a single dose of NTP42:KVA4, as the liquid form without food, as a capsule without food or as a capsule with food.
A total of 13 healthy volunteers, 6 male and 7 female, aged between 18 and 55 years, were enrolled in the trial. All 13 volunteers enrolled in the trial received at least 1 dose of NTP42:KVA4 where 11 of them participated in all 3 dose sessions while another could only participate in 2 sessions with the remaining volunteer acting as a replacement for the third dose session.
Safety Results: Overall, NTP42:KVA4, taken as either the liquid or capsule form without or with food was well tolerated. There were no deaths, non-fatal serious adverse events (AEs), 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 NTP42:KVA4, when taken as either the liquid or capsule form, and overall incidence of TEAEs in the trial.
There were no changes in laboratory tests (blood or urine measurements), blood pressure and heart rate, rhythm or activity in volunteers receiving NTP42:KVA4, as either the liquid or capsule form.
Pharmacokinetics & Pharmacodynamics:
The pharmacokinetic data (effect of the body on the drug) showed that the blood levels of NTP42 were increased when the NTP42:KVA4 dose was taken as a capsule compared to the liquid form. The trial determined that the experimental medicine can be taken as a capsule 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:
With the successful completion of the Phase I trial, confirming that it is safe and well-tolerated, further clinical studies for the capsule form of NTP42:KVA4 in patients are justified and planned.
Further information about this current trial may be found at: https://clinicaltrials.gov/study/NCT06092788
Additional information about the study drug NTP42 or its experimental medicine NTP42:KVA4 may be found at: https://www.atxatherapeutics.com/"REC name
London - Harrow Research Ethics Committee
REC reference
23/LO/0641
Date of REC Opinion
20 Oct 2023
REC opinion
Further Information Favourable Opinion