Evaluation of Prucalopride in Subjects With Moderate and Severe Hepatic Impairment (HI)

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: prucalopride; Drug: prucalopride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group I; Moderate hepatic impairment (grade B)	Drug: prucalopride; single oral dose of 2 mg prucalopride; Drug: prucalopride; single dose of 2 mg prucalopride
ACTIVE_COMPARATOR: Group II; Severe hepatic impairment (grade C)	Drug: prucalopride; single oral dose of 2 mg prucalopride; Drug: prucalopride; single dose of 2 mg prucalopride
ACTIVE_COMPARATOR: Group III; healthy subjects	Drug: prucalopride; single oral dose of 2 mg prucalopride; Drug: prucalopride; single dose of 2 mg prucalopride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Movetis

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): February 1, 2011
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 28, 2010
• First Posted (ESTIMATE): May 31, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 19, 2012
• Last Update Submitted That Met QC Criteria: April 17, 2012
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Two groups of 8 hepatically impaired subjects, one group of 8 matched healthy subjects
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: M0001-C103