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Thorough Corrected QT Interval (QTc) Study To Evaluate Possible Effects of Prucalopride on ECG Parameters

Phase 1
Completed
Conditions
Constipation
Interventions
Registration Number
NCT00903747
Lead Sponsor
Movetis
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
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.
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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1prucalopridePrucalopride
2moxifloxacinPlacebo/moxifloxacin
2placeboPlacebo/moxifloxacin
Primary Outcome Measures
NameTimeMethod
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
Secondary Outcome Measures
NameTimeMethod
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