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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01643889
First received: July 16, 2012
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Treatment A (domperidone 10 mg)
Drug: Treatment B (domperidone 20 mg)
Drug: Treatment C (placebo)
Drug: Treatment D (moxifloxacin)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • The change from baseline in QTc intervals on Day 1 [ Time Frame: Baseline, 5 hours ] [ Designated as safety issue: No ]
  • The change from baseline in QTc intervals on Day 4 [ Time Frame: Baseline, 5 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The plasma concentrations of domperidone [ Time Frame: 9 time points on Day 1 ] [ Designated as safety issue: No ]
  • The plasma concentrations of domperidone [ Time Frame: 9 time points on Day 4 ] [ Designated as safety issue: No ]
  • The plasma concentrations of moxifloxacin [ Time Frame: 9 time points on Day 1 ] [ Designated as safety issue: No ]
  • The plasma concentrations of moxifloxacin [ Time Frame: 9 time points on Day 4 ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: July 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence group ADBC
Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Drug: Treatment A (domperidone 10 mg)
1 domperidone 10 mg capsule four times a day (q.i.d.) + 1 domperidone placebo capsule q.i.d. on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment B (domperidone 20 mg)
2 domperidone 10 mg capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment C (placebo)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment D (moxifloxacin)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin 400 mg capsule in the morning of Day 1.
Experimental: Sequence group BACD
Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Drug: Treatment A (domperidone 10 mg)
1 domperidone 10 mg capsule four times a day (q.i.d.) + 1 domperidone placebo capsule q.i.d. on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment B (domperidone 20 mg)
2 domperidone 10 mg capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment C (placebo)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment D (moxifloxacin)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin 400 mg capsule in the morning of Day 1.
Experimental: Sequence group CBDA
Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Drug: Treatment A (domperidone 10 mg)
1 domperidone 10 mg capsule four times a day (q.i.d.) + 1 domperidone placebo capsule q.i.d. on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment B (domperidone 20 mg)
2 domperidone 10 mg capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment C (placebo)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment D (moxifloxacin)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin 400 mg capsule in the morning of Day 1.
Experimental: Sequence group DCAB
Treatment A: domperidone 10 mg; Treatment B: domperidone 20 mg; Treatment C: placebo; Treatment D: moxifloxacin.
Drug: Treatment A (domperidone 10 mg)
1 domperidone 10 mg capsule four times a day (q.i.d.) + 1 domperidone placebo capsule q.i.d. on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment B (domperidone 20 mg)
2 domperidone 10 mg capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment C (placebo)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin placebo capsule in the morning of Day 1.
Drug: Treatment D (moxifloxacin)
2 domperidone placebo capsules four times a day (q.i.d.) on Days 1 to 3 and a single dose on Day 4 (13 doses in total), and 1 moxifloxacin 400 mg capsule in the morning of Day 1.

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01643889

Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01643889     History of Changes
Other Study ID Numbers: CR100893, DOMDYP1001, 2012-001567-70
Study First Received: July 16, 2012
Last Updated: June 21, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Janssen Research & Development, LLC:
Healthy
Domperidone
Cardiac Repolarization

Additional relevant MeSH terms:
Domperidone
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antiemetics
Antineoplastic Agents
Autonomic Agents
Central Nervous System Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Dopamine Agents
Dopamine Antagonists
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014