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A Study to Evaluate the Effects of Domperidone on Cardiac Repolarization in Healthy Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Treatment A (domperidone 10 mg)
Drug: Treatment B (domperidone 20 mg)
Drug: Treatment C (placebo)
Drug: Treatment D (moxifloxacin)
Registration Number
NCT01643889
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to assess the effects of single and multiple doses of domperidone on the QTc interval duration in healthy adult volunteers at domperidone doses of 10 mg four times a day (q.i.d.) and 20 mg q.i.d.

Detailed Description

This is a randomized (the study drug is assigned by chance), placebo- and positive-controlled, double-blind (neither physician nor participant knows the treatment that the participant receives), single-dose and multiple-dose, 4-way crossover (method used to switch participants from one treatment arm to another in a clinical trial) study. A placebo control will be used to evaluate the effect of domperidone on QTc intervals in comparison with placebo. QTc is a measure of time in the heart electrical cycle. Placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial. Moxifloxacin, which is known to prolong QTc intervals, will be used as positive control to establish assay sensitivity. The participants will be randomly assigned to 1 of 4 treatment sequence groups (ADBC, BACD, CBDA, and DCAB) based on a computer-generated randomization schedule and will receive the following 4 treatments in the order specified by the randomization: Treatment A (10 mg domperidone); Treatment B (20 mg domperidone); Treatment C (placebo); Treatment D (moxifloxacin). The study has 3 phases: a screening phase, a double-blind treatment phase (that corresponds to 4 treatment periods), and an assessment period. Each treatment period will last 4 days and will be separated with a washout period (ie, period when receiving no treatment) of 4 to 9 days. The participants will be confined to the clinical testing facility for approximately 5 days in each period. All treatments (A, B, C and D) will be given orally with water. The maximum study duration for a participant will be 74 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
44
Inclusion Criteria
  • If a woman, must be postmenopausal, surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control
  • If a woman, must have a negative serum beta human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test on Day -1 of each treatment period
  • Body mass index (BMI; weight [kg]/height2 [m]2) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
  • Blood pressure between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
  • An electrocardiogram (ECG) consistent with normal cardiac conduction and function
Exclusion Criteria
  • History of risk factors for cardiac diseases
  • Laboratorial tests with clinically significant abnormal values
  • Clinically significant abnormal physical examination, vital signs or electrocardiogram (ECG) at screening
  • Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol within 14 days before the first dose of the study drug
  • History of or current clinically significant medical illness, disease, or condition that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Sequence group ADBCTreatment A (domperidone 10 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group ADBCTreatment B (domperidone 20 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group ADBCTreatment C (placebo)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group ADBCTreatment D (moxifloxacin)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group BACDTreatment A (domperidone 10 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group BACDTreatment B (domperidone 20 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group BACDTreatment C (placebo)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group BACDTreatment D (moxifloxacin)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group CBDATreatment A (domperidone 10 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group CBDATreatment B (domperidone 20 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group CBDATreatment C (placebo)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group CBDATreatment D (moxifloxacin)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group DCABTreatment A (domperidone 10 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group DCABTreatment B (domperidone 20 mg)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group DCABTreatment C (placebo)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Sequence group DCABTreatment D (moxifloxacin)Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Primary Outcome Measures
NameTimeMethod
The change from baseline in QTc intervals on Day 1Baseline, 5 hours
The change from baseline in QTc intervals on Day 4Baseline, 5 hours
Secondary Outcome Measures
NameTimeMethod
The plasma concentrations of domperidone9 time points on Day 4
The plasma concentrations of moxifloxacin9 time points on Day 4
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