Status and phase
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Treatments
About
Randomised, single-dose, crossover, placebo-controlled study to see if intravenous amisulpride has any effect on the heart rhythm, in particular the QT interval, in healthy adult volunteers.
Full description
Phase 1, randomised, single-dose, period-balanced, crossover, placebo- controlled study to assess the effects of iv doses of amisulpride on the QT interval, corrected for heart rate by Fridericia's formula (QTcF), in healthy male and female subjects of Caucasian and Japanese ethnicity aged 20-45 years.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Healthy male or female subjects aged between 20 and 45 years (inclusive) at screening.
Signed informed consent in the local language prior to any study-mandated procedure.
Japanese subjects defined as a person carrying a Japanese passport, who is a descendant of four Japanese grandparents and has not been outside Japan for more than five years prior to screening.
The Caucasian subjects should be distinguished especially by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa, western Asia, and India. Therefore, the study may as well include Caucasian subjects from North America, Australia and South Africa
No clinically significant findings on the physical examination at screening and at admission on Day -2.
Body mass index (BMI) between 18 and 25 kg/m2 (inclusive) at screening and at admission on Day -2, body weight at least 48 kg.
Systolic blood pressure (SBP) 90-145 mmHg, diastolic blood pressure (DBP) 40-90 mmHg, and heart rate (HR) 40-90 bpm (all inclusive), measured on the left arm, after 10 minutes in the supine position at screening and at admission on Day -2.
Triplicate 12-lead ECG without clinically relevant abnormalities measured after ten minutes in the supine position at screening and on admission on Day -2.
24-hour 12-lead Holter ECG or an equivalent assessment and/or submaximal exercise test without clinically relevant abnormalities measured at screening.
Haematology, biochemistry and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening and at admission.
Subjects must agree to use acceptable methods of contraception:
Male subjects
Male subjects must use medically acceptable methods of contraception if their female partner(s) is (are) pregnant or lactating from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. Acceptable methods include:
Use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. The acceptable methods of contraception are as follows:
Female subjects
Female subjects of childbearing potential must use medically acceptable methods of contraception from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. Acceptable methods include:
Ability to communicate well with the Investigator in the local language, and to understand and comply with the requirements of the study.
Exclusion criteria
Women who are pregnant and/or breastfeeding.
Received amisulpride for any indication within the last 2 weeks.
Allergy to amisulpride or any of the excipients of APD421.
History of vestibular disorder or history of dizziness.
Received anti-emetic therapy including corticosteroids within the last 2 weeks.
History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug (appendectomy and herniotomy allowed, cholecystectomy not allowed).
History of epilepsy.
History of clinically significant syncope.
Family history of sudden death.
Family history of premature cardiovascular death.
Clinically significant history or family history of congenital long QT syndrome (e.g. Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's syndrome.
History of clinically significant arrhythmias and ischemic heart disease (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF or coronary spasm).
Conditions predisposing the volunteer to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa).
ECG abnormalities in the standard 12-lead ECG (at screening and Day -2) and 24-hour 12-lead Holter ECG or an equivalent assessment and/or submaximal exercise test (at screening) which in the opinion of the Investigator will interfere with the ECG analysis.
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following (at screening and Day -2 of Period 1):
Subject with borderline deviations from these criteria may be included if the deviations do not pose a safety risk, and if agreed between the appointed Cardiologist and the PI.
Signs and/or symptoms of a clinically relevant acute illness in the four-week period prior to screening.
Veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
Known hypersensitivity to any medicines administered in the trial.
Treatment with any prescribed medication during the two weeks prior to first baseline day.
Treatment with any over-the-counter (OTC) medications during the two weeks prior to first baseline day.
Treatment with vitamins and/or minerals within 48 hours prior to the first baseline day.
Treatment with another investigational drug within four weeks prior to dosing or having participated in more than three investigational drug studies within one year prior to dosing.
Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol breath test at screening and on Day -2.
History or clinical evidence of alcoholism or drug abuse. Alcohol abuse is defined as regular weekly intake of more than 14 units (Using alcohol tracker http://www.nhs.uk/Tools/Pages/NHSAlcoholtracker.aspx); drug abuse is defined as compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms.
Excessive caffeine consumption, defined as ≥800 mg per day at screening (800 mg = 7 cups of coffee or 16 cups of tea).
Smoking within three months prior to screening or during the screening period.
Loss of 250 mL or more blood within three months prior to screening.
Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
Positive results from the HIV serology at screening.
Any circumstances or conditions, which, in the opinion of the Investigator, may affect full participation in the study or compliance with the protocol.
Legal incapacity or limited legal capacity at screening.
Primary purpose
Allocation
Interventional model
Masking
40 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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