Safety Study of Prucalopride in Healthy Volunteers

Single-centre, double-blind, placebo-controlled, cross-over study in 33 healthy volunteers with 2 sessions. Each session consisted of a run-in day for baseline assessments, 8 treatment days and 5 additional days for followup assessments. Subjects were randomised to start with either the prucalopride or placebo session. The prucalopride dose was consecutively escalated in 2 mg steps per day, starting from 2 mg up to 10 mg once daily If a subject did not tolerate the 10- or 8-mg dose, 1 step back in the dosage scheme was allowed, from 10 to 8 mg on Day 6, or from 8 to 6 mg on Day 5. Subjects with intolerance for doses of less than 6 mg, were withdrawn from the study. Repeated dosing (6, 8 or 10 mg) was continued once daily until Day 8, to achieve steady-state. During placebo, the number of placebo tablets was consecutively escalated in an identical way as described for prucalopride. Between the 2 sessions, there was a washout period of 14 to 21 days, to avoid any carry-over effect.

Inclusion criteria

• Aged between 18 and 45 years.
• Normal weight.
• Healthy on the basis of a pre-study physical examination, medical history, anamnesis,ECG, 24-hour Holter monitoring, echocardiogram and the results of blood biochemistry and haematology tests and a urinalysis carried out in 3 weeks preceding randomisation.

Exclusion criteria

• History or suspicion of alcohol, barbiturate, amphetamine or narcotic abuse.
• Smoking more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 6 months prior to selection.
• History of cardiac arrhythmias, bronchospastic or cardiovascular disease (e.g. ischaemic heart disease or cerebrovascular accident), diabetes mellitus, thyrotoxicosis,Parkinsonism.
• Presence of prolonged QTc (Bazett) on ECG at screening (QTc >450 ms in male subjects, QTc >470 ms in female subjects).
• Use of concomitant medication, except for oral contraceptives and paracetamol.
• Participation in an investigational drug study in 30 days prior to the first visit.
• Donation of blood in the 60 days preceding the first visit.
• Pregnancy or breast-feeding female.
• Female subjects of childbearing potential without adequate contraceptive protection during the study.