A Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prucalopride (Resolor) Tablets in Subjects With Chronic Constipation

• The percentage of patients with a weekly average of 3 or more SCBMs during the first 4 weeks of the double blind treatment period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Percentage of patients with change of >1 SCBM/week [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Average number of SCBMs, spontaneous bowel movements (SBMs) and BMs per week after medication [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Time to first SBM [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Changes of adverse events, laboratory parameters, vital signs, and electrocardiogram (ECG) data [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

The purpose of this study is to compare the efficacy and safety of prucalopride 2 mg given orally once daily for 12 weeks to those of placebo in treatment of chronic constipation. Prucalopride is an investigational drug that is being tested to see if it may be useful in treating chronic constipation.

Prucalopride is new potent, selective and specific serotonin 4 receptor agonist that stimulates the bowel motility. It is being investigated to see if it may be useful in treating chronic constipation. This study will compare the efficacy and safety of prucalopride 2-mg given orally once daily for 12 weeks to those of placebo in the treatment of chronic constipation. Placebo looks like the drug being studied but has no active ingredients. This study consists of 3 phases: a 2-week drug-free screening phase, a 12-week treatment phase, and a posttreatment follow-up contact performed 7 days following the last dose of study drug. The total duration of the patient's participation in the study is approximately 15 weeks. During the screening phase, the patient's bowel habit will be documented and the existence of chronic constipation confirmed. At the start of this phase, all existing laxative medication will be withdrawn and patient will be instructed not to change their diet or lifestyle during the study. Patients will be allowed to take a laxative (bisacodyl) as a rescue medication throughout the trial, but only if they have not had a bowel movement (BM) for three or more consecutive days. No bisacodyl should be taken or enemas used within 48 hours prior to the start of the double-blind treatment (48 hours prior to Day1) and 48 hours following the start of double-blind treatment (48 hours following Day1). The patient will enter the double-blind treatment phase if constipation is shown to be present during the screening phase. If the definition of constipation is not met during the screening period, the patient will be considered ineligible and will be discontinued from the study. During the double-blind treatment phase, the patient will be treated for 12 weeks with 2-mg prucalopride or matching placebo, given orally once daily before breakfast. Patients will record study drug and rescue medication dosing information and information related to bowel movements in a daily diary throughout the study. 2-mg Prucalopride/placebo tablet, given orally once daily for 12 weeks.

• Drug: prucalopride 2-mg
  2mg tablet once daily for 12 weeks
• Drug: placebo
  1 tablet once daily for 12 weeks

• Experimental: 001
  prucalopride 2-mg 2mg tablet once daily for 12 weeks
  Intervention: Drug: prucalopride 2-mg
• Placebo Comparator: 002
  placebo 1 tablet once daily for 12 weeks
  Intervention: Drug: placebo

Inclusion Criteria:

- Male and non-pregnant, non breast-feeding female outpatients

• History of chronic constipation, not satisfied with laxatives: the patient reports, on average 2 or fewer spontaneous bowel movements (SBMs) per week and 1 or more of the following for at least 6 months before the screening visit and during the run-in phase:a) very hard (little balls) and/or hard stools in more than 25% of BMs
• b) sensation of incomplete evacuation in more than 25% of BMs
• c) straining at defecation in more than 25% of BMs d) sensation of ano-rectal obstruction or blockade in more than 25% of BMs : e) a need for digital manipulation to facilitate evacuation in more than 25% of BM

Exclusion Criteria:

• Secondary to other diseases/conditions (endocrine disorders, metabolic disorders or neurologic disorders or drug-induced or suspected organic disorders of the large bowel, i.e., obstruction, carcinoma, or inflammatory bowel disease)
• Patients who have polyps discovered on the colonoscopy that are untreated (i.e., by polypectomy)
• Use of or intent to use disallowed medications that influence the bowel habit during the study (i.e., anticholinergics [not including antihistamines], opioids, spasmolytics, prokinetics, and tricyclic antidepressants
• Have severe and clinically uncontrolled cardiovascular, liver, or lung disease, neurologic or psychiatric disorders (including active alcohol or drug abuse), cancer or acquired immune deficiency syndrome (AIDS), or other gastrointestinal or endocrine disorders
• Patients with impaired renal function, i.e., serum creatinine >2 mg/dL (>180 mmol/L)
• Patients with clinically significant abnormalities of hematology, urinalysis, or blood chemistry
• Known allergies, hypersensitivity, or intolerance to prucalopride or its excipients
• Females of child-bearing potential without adequate contraceptive protection during the trial
• Patients who have received an investigational drug or used an investigational medical device in the 30 days preceding the screening visit