Efficacy Study of Prucalopride to Treat Chronic Intestinal Pseudo-Obstruction (CIP)

This phase II, double-blind, placebo-controlled, two-treatment four periods cross-over trial investigated the clinical safety, tolerability and the efficacy of R093877 (prucalopride) in improving the symptoms associated with chronic intestinal pseudo-obstruction (CIP) in subjects with CIP.

Subjects were treated for 4 periods of 12 weeks each with either R093877 2 mg (2 periods) or placebo (2 periods). In each of the first and second 6 month period, there was a placebo (PLA) and an active drug (PRU) treatment period. There were no wash-out periods. In total,7 subjects were randomized; 2 were assigned to the PLA-PRU-PLA-PRU, 2 to the PRUPLA-PRU-PLA, 2 to the PLA-PRU-PRU-PLA, and 1 to the PRU-PLA-PLA-PRU sequence group. Subjects were allowed to use up to 4 mg of prucalopride per day if the 2 mg dose seemed to be insufficient. Two subjects used an average of 3 mg of prucalopride per day during the active drug periods.

Inclusion criteria

• Aged ≥ 18 years;
• A history of chronic pseudo-obstruction for at least 3 months;
• Subjects with chronic idiopathic pseudo-obstruction or chronic pseudo-obstruction secondary to scleroderma or intestinal polyneuropathy;
• CIP had been diagnosed by a Barium-imaging study showing the presence of dilatation of any part of the small bowel (with or without the presence of large bowel dilatation);

Exclusion criteria

• Subjects with organic obstructing lesions causing intestinal obstruction;
• Current uncontrolled cardiovascular or lung disease, neurologic or psychiatric disorders (including substance abuse but with the exception of nicotin), alcoholism, cancer or AIDS and endocrine disorder;
• Impaired renal function
• A serum amylase, a serum glutamic-oxaloacetic transaminase (SGOT) or a serum glutamic-pyruvic transaminase (SGPT)concentration of > 2 times the normal limit;
• Laboratory values outside the reference range of the laboratory, unless explained by the disease or felt by the investigator to be clinically unimportant;
• Use of disallowed concomitant therapy;
• Female subjects who were pregnant or wished to become pregnant during the course of the trial or who were lactating;