A Trial in Healthy Volunteers, to Evaluate the Tolerability and Cardiac Safety of Prucalopride

Constipation Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, 2-Way Cross-Over Trial in Healthy Volunteers, to Evaluate the Pharmacokinetics, Tolerability and Cardiac Safety of Oral Prucalopride at Steady State, After up-Titration to a Maximum of 20 mg.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488215
• Other study ID #: PRU-GBR-10
• Status: Completed
• Phase: Phase 1
• First received: June 19, 2007
• Last updated: May 28, 2008
• Start date: January 2000
• Est. completion date: March 2000

Study information

• Verified date: June 2007
• Source: Movetis
• Contact: n/a
• Is FDA regulated: No
• Health authority: UK: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

An escalating dose of prucalopride up to a maximum of 20 mg was given once daily to 32 healthy volunteers to determine safety at the maximum tolerable dose or at 20 mg.

Description:

This is a single-centre, double-blind, placebo-controlled, cross-over trial in 32 healthy volunteers with two sessions (I and II). Each session consists of a run-in day for baseline assessments, 13 treatment days and 5 additional days for assessments. Subjects will be randomized to start with either the prucalopride or placebo session.

Between the 2 sessions, there will be a washout period of 14 to 21 days, to avoid any carry-over effect.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2000
• Est. primary completion date: March 2000
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Aged between 18 and 45 years, extremes included.

2. Subject has a normal weight as defined by a Quetelet Index range of 18 - 30 kg/m2, extremes included.

3. Informed consent form signed and dated, prior to screening.

4. Healthy on the basis of a pre-trial physical examination, medical history, anamnesis, electrocardiogram, 24 hour Holter monitoring and the results of blood biochemistry and haematology tests and a urinalysis carried out in 3 weeks preceding randomization.

Exclusion Criteria:

1. History or suspicion of alcohol, barbiturate, amphetamine or narcotic abuse.

2. Smoking more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 6 months prior to selection.

3. History of cardiac arrhythmia's, bronchospastic or cardiovascular disease (e.g. ischemic heart disease or cerebrovascular accident), diabetes mellitus, thyrotoxicosis, Parkinsonism, drug allergy.

4. Presence of prolonged QTc (Bazett) on ECG at screening (QTc > 450 msec in male subjects, QTc > 470 msec in female subjects).

5. Use of concomitant medication, except for oral contraceptives and paracetamol. All other medication must have been stopped at least 14 days before the first dose.

6. Participation in an investigational drug trial in 30 days prior to the first visit.

7. Donation of blood in the 60 days preceding the first visit.

8. Pregnancy (as confirmed by a HCG test during screening and at day 0 of each treatment session) or breast-feeding female.

9. Subjects with positive results for HIV, hepatitis B or C at screening.

10. Female subjects of childbearing potential without adequate contraceptive protection during the trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Constipation

Intervention

Drug:
• prucalopride
The dose will be consecutively escalated in 2 mg steps per day, starting from 2 mg up to 20 mg once daily or until severe drug-related adverse events occur (= individual maximum tolerable dose, on decision of the subject and/or investigator).

Other:
• Placebo
During the placebo session, the number of placebo tablets will be consecutively escalated in an identical way as described for prucalopride. This means 1 tablet more every day, up to 10 tablets.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Movetis

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The exploration whether the maximum tolerable dose (MTD, defined as the highest dose not causing severe drug-related adverse events in > 50 % of the subjects) is achieved between 0 and 20 mg prucalopride.		26 days	Yes
Secondary	The documentation of laboratory and cardiovascular safety (vital signs, ECG, Holter monitoring) at the MTD or at 20 mg.		26 days	Yes