Clinical trial NCT00903747: Thorough Corrected QT Interval (QTc) Study To Evaluate Possible Effects of Prucalopride on ECG Parameters
Official title: A Phase I Thorough QT/QTc Study To Evaluate The Effect of Therapeutic and Supratherapeutic Multiple Doses of Prucalopride on Cardiac Repolarisation in Healthy Male and Female Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Constipation
Keywords: Prucalopride
safety study
Lead sponsor: Movetis
Sponsor class: INDUSTRY
First posted: 2009-05-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: January to April 2009
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Movetis NV
name: Remi VD Broeck, MD
role: STUDY_DIRECTOR
References:
citation: Mendzelevski B, Ausma J, Chanter DO, Robinson P, Kerstens R, Vandeplassche L, Camm J. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study. Br J Clin Pharmacol. 2012 Feb;73(2):203-9. doi: 10.1111/j.1365-2125.2011.04088.x.