Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study.
Chronic constipation is common among nursing home residents. The aim of this study was to evaluate safety, tolerability and pharmacokinetics of the selective 5HT(4) receptor agonist prucalopride in elderly, chronically constipated patients in nursing homes. A multicentre, phase II, randomized, double-blind dose-escalation study in 89 elderly constipated nursing home residents treated with placebo, 0.5, 1 or 2 mg prucalopride once daily for 28 days was analysed. Adverse events, vital signs, ECG, Holter monitor and pharmacokinetics were assessed (Clinicaltrials.gov identifier: NCT00627692). Patients' mean age was 83 years; 88% had a history of cardiovascular diseases. Most frequent adverse events, at least possibly related to prucalopride, were diarrhoea and abdominal pain. Relative to placebo, there were no differences in vital signs, ECG corrected QT interval, ECG morphology parameters, or incidence of supraventricular or ventricular arrhythmias on Holter monitoring. Plasma prucalopride concentrations increased proportionally with administered dose. Prucalopride up to 2 mg once daily for 4 weeks was safe and well-tolerated by constipated elderly patients, with no differences vs placebo in ECG or a range of Holter-monitoring parameters.
Camilleri
M
M
Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
Beyens
G
G
Kerstens
R
R
Robinson
P
P
Vandeplassche
L
L
D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001572:Benzofurans / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D003248:Constipation / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use*
D001572:Benzofurans; D005765:Gastrointestinal Agents; D017366:Serotonin Receptor Agonists; C406662:prucalopride