Constipation
Conditions
Keywords
Prucalopride, safety study
Brief summary
This is a 2-arm, parallel-group active- and placebo-controlled, double-blind randomised study, stratified by gender and with a hybrid crossover group design, to compare treatment with prucalopride 2 mg/day (intended therapeutic dose) and prucalopride 10 mg/day (supratherapeutic dose) with placebo. A single oral dose of 400 mg moxifloxacin is included as a positive control in terms of the effect on cardiac repolarisation. Study hypothesis: Treatment with therapeutic (2 mg) or supratherapeutic (10 mg) doses of prucalopride in healthy male and female volunteers will not increase QTc interval compared to placebo.
Detailed description
A total number of 120 healthy subjects (with an approximate 1:1 female:male ratio) are planned to be randomised. Day 1: a baseline ECG profile. Day 1: Group 1 will receive prucalopride, Group 2a will receive moxifloxacin, and Group 2b will receive placebo. On Day 5 (steady-state level is reached), a full ECG assessment day will be performed, enabling the comparison of prucalopride 2 mg with placebo. Subsequently, the number of tablets will be escalated in all groups (blinded) with 1 tablet a day up to 5 tablets. On Day 13 (steady state for the supratherapeutic dose level of 10 mg of prucalopride) another ECG assessment day will be performed, enabling a comparison of prucalopride 10 mg with placebo. Group 2b will receive a single dose of moxifloxacin on Day 15. All subjects will be discharged on Day 16. Subjects will remain in the CRU throughout the treatment period. All subjects will return for a follow-up visit on Day 30 (± 1 week) (approximately 14 days after the last dose).
Interventions
DRUGprucalopride
2-10 mg prucalopride
DRUGmoxifloxacin
400 mg moxifloxacin (Group 2a)
DRUGplacebo
placebo (Group 2b)
Sponsors
Movetis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Healthy volunteers aged between 18 to 50 years. 2. Body mass index (BMI) between 18 and 30 kg/m2. 3. Female subjects must: * be of childbearing potential with a negative serum β-human chorionic gonadotropin (β-HCG) test at screening, and be willing and able to use medically acceptable double barrier methods of birth control, throughout the whole study; or * be postmenopausal; or * have received surgical sterilisation at least 6 months before screening; AND * females must not be receiving hormone replacement therapy (HRT). Main
Exclusion criteria
1. Abnormal QTcF and/or heart rate/blood pressure values at baseline. 2. Subjects with ECG abnormalities that may interfere with the accurate assessment of the QT interval. 3. Subjects with known cardiovascular disorders. 4. Subjects with known clinically significant arrhythmias. 5. Subjects with risk factors e.g., Torsades de Pointes. 6. Subjects with clinically relevant, abnormal serum electrolytes or complete blood count (CBC) at screening. 7. Female subjects who are lactating or pregnant. 8. Subjects suffering from other significant medical conditions. 9. Subjects with a known allergy or sensitivity to moxifloxacin, or to prucalopride. 10. Subjects with a positive screening test for hepatitis B, hepatitis C, or HIV at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment with therapeutic (2 mg) or supratherapeutic (10 mg) doses of prucalopride in healthy male and female volunteers does not increase QTc interval compared to placebo. | January to April 2009 |
Outcome results
None listed