Clinical trial NCT01643889: A Study to Evaluate the Effects of Domperidone on Cardiac Repolarization in Healthy Volunteers
Official title: A Randomized, Double-Blind, Placebo- and Positive-Controlled, Single- and Multiple-Dose, 4-Way Crossover Study to Evaluate the Effects of Domperidone on Cardiac Repolarization in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Domperidone
Cardiac Repolarization
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-07-18
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The change from baseline in QTc intervals on Day 1
timeFrame: Baseline, 5 hours
measure: The change from baseline in QTc intervals on Day 4
timeFrame: Baseline, 5 hours
Secondary outcomes:
measure: The plasma concentrations of domperidone
timeFrame: 9 time points on Day 1
measure: The plasma concentrations of domperidone
timeFrame: 9 time points on Day 4
measure: The plasma concentrations of moxifloxacin
timeFrame: 9 time points on Day 1
measure: The plasma concentrations of moxifloxacin
timeFrame: 9 time points on Day 4
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: