Evaluation of Prucalopride in Subjects With Moderate and Severe Hepatic Impairment

Study Overview
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Brief Summary
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This is a single centre, open-label phase I trial to investigate the effects of moderate to severe hepatic impairment on the pharmacokinetics of prucalopride in comparison with healthy volunteers. Furthermore the short-term safety and tolerability of a single dose of prucalopride will be assessed.

Detailed Description
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In this phase I trial two groups of 6 to 8 hepatically impaired subjects will be evaluated. The first group are the moderate hepatic impairment (Grade B) subjects and the second group the severe hepatic impairment (grade C) subjects. Subjects for both groups will be recruited and treated in parallel. After all subjects with hepatic impairment completed the treatment a third group with matching healthy volunteers will be recruited. Eight healthy subjects will be selected matching for age, gender and weight (BMI based). The subjects will receive a single dose of 2 mg prucalopride in the morning after overnight fasting followed by the consumption of a standard breakfast after 2 hours. Pharmacokinetic evaluation of blood samples will be done immediately before and at a specific timepoint up to 120h post-dosing. Urine samples will be taken to determine prucalopride. Adverse events, including serious adverse events, will be reported from signing the Informed Consent until the last visit. Safety blood samples and a urine sample for urinalysis will be taken.

Official Title
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Evaluation of Pharmacokinetics, Safety and Tolerability of a Single Dose of Prucalopride, in Subjects With Moderate and Severe Hepatic Impairment, in Comparison With Healthy Subjects

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: prucalopride
* Drug: prucalopride
* Drug: prucalopride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main inclusion criteria for hepatic impairment subjects: Moderate (Grade B) or severe (Grade C) chronic hepatic impairment according to Child-Pugh classification; Hepatic impairment must be stable, both clinically and biochemically; Within the normal range of body height and weight on the basis of the Body Mass Index. Main inclusion criteria for healthy subjects: Matching on sex, age and weight(BMI based). Exclusion Criteria: History or suspicion of barbiturate, amphetamine or narcotic abuse; Suspicion of current alcohol abuse; Clinical suspicion or laboratory evidence of unstable hepatic impairment or acute liver injury; Clinically relevant renal disease as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I<br>Moderate hepatic impairment (grade B) | Drug: prucalopride<br>* single oral dose of 2 mg prucalopride<br>|
| Active Comparator: Group II<br>Severe hepatic impairment (grade C) | Drug: prucalopride<br>* single oral dose of 2 mg prucalopride<br>|
| Active Comparator: Group III<br>healthy subjects | Drug: prucalopride<br>* single dose of 2 mg prucalopride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Evaluation of prucalopride in blood immediately before and at 17 timepoints post dosing and in urine at 8 collection time points. | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Evaluation of safety parameters by measuring adverse events, safety, blood and urine samples, ECGs, vital signs and physical examinations. | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Two groups of 8 hepatically impaired subjects, one group of 8 matched healthy subjects