Thorough QT Study of Intravenous Amisulpride

NCT02661594 | Completed Phase 1 Results

• 1 other identifier: DP10013
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy

Keywords

TQT; amisulpride; volunteer; ECG

Outcome Measures

Primary Outcomes (1)

• Maximal Mean ΔΔQTcF

  Maximal mean placebo-corrected change from baseline of QTcF (QT interval corrected for heart rate using the Fridericia formula) for single 5 mg and 40 mg iv doses of APD421. At each time point (2 mins, 8 mins, etc) the QTcF is compared to the pre-dosing "baseline" value, in order to calculate the change in QTcF (ΔQTcF). The value of ΔQTcF at each time point is then compared against the same time point for a placebo infusion, and the difference is calculated (ΔΔQTcF).

  24 hours

Study Arms (4)

ABCD

EXPERIMENTAL

A: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo.

Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo

BDAC

EXPERIMENTAL

B: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg;

Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo

CADB

EXPERIMENTAL

C: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg

Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo

DCBA

ACTIVE COMPARATOR

D: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg

Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo

Interventions

APD421 5 mg DRUG

Therapeutic dose of amisulpride

Also known as: Amisulpride 5mg

ABCD; BDAC; CADB; DCBA

APD421 40 mg DRUG

Supra-therapeutic dose of amisulpride

Also known as: Amisulpride 40mg

ABCD; BDAC; CADB; DCBA

Moxifloxacin DRUG

Positive control for assay sensitivity

ABCD; BDAC; CADB; DCBA

Placebo DRUG

Placebo comparator to establish baseline for calculating change in QTcF

ABCD; BDAC; CADB; DCBA

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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:
• Condom used with spermicidal foam/gel/film/cream/suppository
• If the subject has undergone surgical sterilisation (vasectomy with documentation of azoospermia) a condom with spermicidal foam/gel/film/cream/suppository must be used.

You may not qualify if:

• 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):

Sponsors & Collaborators

• Acacia Pharma Ltd: lead

MeSH Terms

Interventions

Amisulpride; Moxifloxacin

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

There were no limitations and caveats with this study.

Results Point of Contact

• Title: Dr Gabriel Fox
• Organization: Acacia Pharma Ltd

GabrielFox@acaciapharma.com

+44-(0)1223-919764

Study Officials

• Gabriel Fox, MB BChir

  Acacia Pharma Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 22, 2016
• Study Start: November 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 29, 2018
• Results First Posted: November 30, 2017

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share