Prucalopride Subjects With Renal Impairment

Single Dose Pharmacokinetic Trial of Oral Prucalopride (R093877) in Subjects With Mild, Moderate and Severe Renal Impairment

The purpose of this study is to evaluate the pharmacokinetics of a single 2 mg oral dose of prucalopride in subjects with various degrees of renal impairment compared with normal renal function and to monitor the safety profile of prucalopride in subjects with renal impairment.

Hypothesis:

Prucalopride might accumulate and exhibit a different pharmacokinetic profile in renally impaired subjects compared with the normal population.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: prucalopride

Detailed Description

This is a single-centre, open label, single-dose, pharmacokinetic trial with prucalopride in subjects with varying degrees of renal impairment. Subjects were classified into one of four renal function groups, as defined by a 24-hour creatinine clearance determination (CRCL) obtained within 2 weeks before trial entry. Each subject was administered a single 2mg oral dose of prucalopride. Plasma samples and complete urine collections were obtained from 0 through 120 h (6 days) after dosing to characterize the pharmacokinetics of prucalopride.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

Description

Inclusion Criteria:

All subjects had to meet the following inclusion criteria:

• Between the ages of 18 and 75 years, inclusive;
• Males or females. Females were to be of non-childbearing potential.

Normal subjects had to meet the following additional inclusion criteria:

• Demographically comparable to the subjects with renal impairment, within 30% of mean weight and height and 10% of the mean age;
• Physical examination, clinical laboratory results, and 12-lead ECG within normal limits at screening;
• No intake of medication, including over-the-counter medication, during a pre-trial 7-day drug-free washout period;

Subjects with renal impairment had to meet the following additional inclusion criteria:

• Stable severity of renal disease;
• Concomitant medications to treat underlying disease states or medical conditions related to renal insufficiency were allowed;
• Stable dose of medication and/or treatment regimen from 2 months prior to and during the trial;
• Subjects with stable cardiovascular disease could be enrolled, provided that the investigator felt their condition would not interfere with the results of the trial.

Exclusion Criteria:

All subjects who met any of the following criteria were excluded from the trial:

• History of hypersensitivity to prucalopride or inactive ingredients in the prucalopride capsule or to related prokinetic compounds;
• Use of any other investigational drug within 30 days prior to signing the consent or intention to take any investigational drug during the trial;
• History of significant blood loss, or blood plasma donation (500mL) within the last 30 days;
• Pregnancy or breast feeding;
• Gastrointestinal (GI) surgery within 3 months, or history of major GI surgery with potential compromise of drug absorption or metabolism;

Normal subjects who met any of the following criteria were excluded from the trial:

• Any abnormal medical history, physical examination, ECG, or laboratory results;
• Use of medications 7 days prior to and during the trial.
• Subjects with renal impairment who met any of the following criteria were excluded from the trial.
• Any abnormality in medical history, physical examination, ECG, or laboratory results that, in the opinion of the investigator, might affect the safety of the subject;
• History of uric acid stone disease, uricosuria, or gout, or current hyperuricemia;
• Renal transplants, lupus erythematosus, or renal carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: prucalopride; single dose of 2 mg prucalopride	Drug: prucalopride; single dose of 2 mg prucalopride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To characterize the Pharmacokinetic profile of prucalopride in subjects with various degrees of renal impairement

Secondary Outcome Measures

Outcome Measure
Secondary efficacy variables: to evaluate the safety and tolerability of prucalopride in subjects with various degrees of renal impairement

Collaborators and Investigators

• Sponsor: Movetis
• Investigators: Principal Investigator: W. Smith, M.D., New Orleans Center for Clinical Research, 2820 Canal Street, New Orleans, LA 70119

Publications and helpful links

General Publications

• Smith WB, Mannaert E, Verhaeghe T, Kerstens R, Vandeplassche L, Van de Velde V. Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study. Drug Des Devel Ther. 2012;6:407-15. doi: 10.2147/DDDT.S36142. Epub 2012 Dec 18.

Study record dates

Study Major Dates

• Study Start: July 1, 1997
• Primary Completion (Actual): August 1, 1999
• Study Completion (Actual): August 1, 1999

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): August 28, 2012
• Last Update Submitted That Met QC Criteria: August 27, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; 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: PRU-USA-6