Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation.
BACKGROUND
Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT(4) agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC.


METHODS
A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of ≥ 1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with ≥ 3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored.


RESULTS
More patients had an increase from baseline of ≥ 1 SCBM per week (weeks 1-4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of ≥ 3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters.


CONCLUSIONS
In this population with OIC, prucalopride improved bowel function and was safe and well tolerated.
Sloots
Cornelius E J
CE
Department of Pediatric Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. c.sloots@erasmusmc.nl
Rykx
An
A
Cools
Marina
M
Kerstens
Rene
R
De Pauw
Martine
M
D015746:Abdominal Pain / Q000139:chemically induced / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D054368:Laxatives / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055986:Vital Signs; D055815:Young Adult
D000701:Analgesics, Opioid; D001572:Benzofurans; D054368:Laxatives; D017366:Serotonin Receptor Agonists; C406662:prucalopride