Effect of Intravenous APD421 on Cardiac Conduction in healthy adults
Research type
Research Study
Full title
A Randomized, Double-blind, Placebo-controlled, Crossover Study in Healthy Adult Subjects to Investigate the Effect of Intravenous APD421, with and without Ondansetron, on Cardiac Conduction
IRAS ID
246024
Contact name
Muna Albayaty
Contact email
Sponsor organisation
Acacia Pharma Ltd
Eudract number
2018-000154-21
Duration of Study in the UK
0 years, 2 months, 3 days
Research summary
This is a single-centre, randomised, double-blind, placebo-controlled, three-period, crossover clinical trial to investigate the effects of single doses of the sponsor’s study drug, APD421, on heart function in 30 healthy male and female subjects. The female volunteers may be of childbearing potential. APD421 (amisulpride for intravenous injection) is currently under development for the management of nausea and vomiting.
In clinical practice APD421 may be given together with ondansetron, a drug which is widely used against nausea and vomiting. Since ondansetron has an effect on the heart’s conduction, researchers want to investigate heart function when APD421 is given with and without ondansetron.The clinical trial will also investigate the pharmacokinetics of APD421 after single and repeated doses. Pharmacokinetics (PK) refers to how the study medication is absorbed (taken up into the body), metabolised (chemically broken down), distributed through the body, and excreted (removed form the body).
The study will comprise a screening visit and three different treatment periods.
Subjects will receive all three treatments.This is not a first-in-human study. There is extensive clinical experience of oral amisulpride, at a wide range of doses and over extended treatment periods. Oral doses up to 1200 mg per day are approved in many countries. Safe use beyond one year has been reported. Intramuscular amisulpride use is also approved in France, at a maximum daily dose of 400 mg. Intravenous amisulpride has been administered to more than 2,000 healthy subjects and patients in Phase I to III clinical trials, revealing a very favourable safety profile. The most common side effects reported after amisulpride administration include extrapyramidal disorders (drug-induced movement illnesses), sleeplessness, anxiety, weight increase, headache, psychosis, constipation, amenorrhea and lactation not related to pregnancy. Ondansetron is generally well tolerated. But, over the past couple of years there has been concerns with the heart safety profile of ondansetron. For this reason persons with long QT syndromes (heart conduction errors) will not be included in this study.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
18/EE/0145
Date of REC Opinion
2 Jul 2018
REC opinion
Further Information Favourable Opinion