Efficacy and Safety Study of Prucalopride for the Treatment of Chronic Constipation

NCT ID: NCT00631813

Last Updated: 2008-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 253 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-11-30
• Study Completion Date: 1997-04-30

Brief Summary

The purpose of this study is to determine which dose of prucalopride is safe and effective in patients with chronic constipation.

Hypothesis:

Prucalopride 1 and 2 mg bid are safe and effective for the treatment of chronic constipation whereas 0,5 mg is a suboptimal dose.

Detailed Description

This is a phase II trial with a parallel-group design, consisting of a drug-free run-in phase (phase 1), followed by a placebo controlled double-blind phase (phase 2). Patients will receive either R093877 0.5 mg b.i.d., 1 mg b.i.d. or 2 mg b.i.d. or placebo for a period of 12 weeks.

Phase 1 is a run-in period of 4 weeks duration, during which the bowel habit is documented and the existence of constipation confirmed. At the start of this period all existing laxative medication is withdrawn and patients will be instructed not to change their dietary habits, in particular their fiber intake during the trial. Patients will enter the double-blind phase if constipation has been shown to be present during the run-in period.

If the definition of constipation was not met during the 4 weeks of the run-in period, the patient will be considered ineligible for the double-blind period.

Phase 2 is a double-blind, randomized, placebo-controlled phase, in which patients will be treated for 12 weeks with either 0.5 mg, 1 mg or 2 mg of R093877 or placebo given twice daily (one capsule is taken before breakfast and one is to be taken before the evening meal).

Patients admitted to the double blind treatment period will be randomly allocated to one of the 4 treatment arms.

Conditions

Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Prucalopride 0.5 mg

Group Type: ACTIVE_COMPARATOR

Prucalopride

Intervention Type: DRUG

0.5 mg bid

2

Prucalopride 1 mg

Group Type: ACTIVE_COMPARATOR

Prucalopride

Intervention Type: DRUG

1 mg bid

3

Prucalopride 2 mg

Group Type: ACTIVE_COMPARATOR

Prucalopride

Intervention Type: DRUG

2 mg bid

4

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

bid

Interventions

Prucalopride

0.5 mg bid

Intervention Type: DRUG

Prucalopride

1 mg bid

Intervention Type: DRUG

Prucalopride

2 mg bid

Intervention Type: DRUG

Placebo

bid

Intervention Type: DRUG

Other Intervention Names

Resolor; Resolor; Resolor

Eligibility Criteria

Inclusion Criteria

1. Age between 18-70 years;

2. History of constipation, i.e., the subject reported the occurrence of two or more of the following criteria for at least 6 months before the selection visit:

• two or fewer spontaneous* bowel movements a week,
• lumpy (scyballae) and/or hard stools at least ¼ of the stools,
• sensation of incomplete evacuation after at least ¼ of the stools,
• straining at defaecation at least ¼ of the time. *The above criteria were only applicable for spontaneous bowel movements i.e., not preceded within a 24-hour period by the intake of a laxative agent. Subjects who never had a spontaneous bowel movement were considered constipated and eligible to enter the double-blind phase of the trial.

3. Constipation being severe and causing disability; the subject's occupational, social and recreational activities were governed by his/her constipation and efforts to attain relief;

4. Normal inhibition pattern of the external anal sphincter during straining i.e., relaxation of the m.puborectalis and a distal displacement of the rectal canal (digital examination and/or electromyographic and/or manometric evidence was acceptable);

5. Poor results with routine laxative treatment and diet counselling;

6. Constipation of a functional, i.e., idiopathic nature;

7. Written or oral witnessed informed consent;

8. Availability for follow-up during the trial period.

Exclusion Criteria

1. Constipation thought to be drug-induced;

2. Presence of secondary causes of constipation, i.e., subjects suffering from types or causes of constipation other than idiopathic constipation, for instance: endocrine disorders, metabolic disorders, or neurologic disorders;

3. Congenital megacolon/megarectum;

4. History of previous abdominal surgery (other than hysterectomy, surgery for Meckel's diverticle, appendectomy, cholecystectomy, inguinal hernia repair, splenectomy, nephrectomy or fundoplication) thought to be the primary cause of constipation;

5. Known or suspected organic disorders of the large bowel, i.e., obstruction, carcinoma or inflammatory bowel disease;

6. Active proctological conditions thought to be responsible for the constipation;

7. Presence of the following ECG abnormalities:

• 2nd or 3rd degree of AV-block,
• prolonged QT-times (> 460 ms),
• bradycardia;

8. Use of concomitant medication that might cause QT-prolongation;

9. Use of diuretics not associated with potassium sparing effects;

10. Known illnesses or conditions such as severe cardiovascular or lung disease, neurologic or psychiatric disorders (including substance abused dependence but with the exception of nicotine), alcoholism, cancer or AIDS and other gastrointestinal or endocrine disorders;

11. Impaired renal function;

12. Presence of a serum amylase, a serum glutamic-oxaloacetic transaminase (SGOT) or a serum glutamic-pyruvic transaminase (SGPT) concentration of > 2 times the normal limit;

13. Presence of clinically significant abnormalities of blood chemistry, other than those mentioned under 9-10, haematology or urinalysis at selection;

14. Pregnancy or wish to become pregnant during the trial. ;

15. Breast-feeding;

16. Investigational drug received in the 30 days preceding the trial;

17. Inability or unwillingness to return for required follow-up visits;

18. Reliability and physical state preventing proper evaluation of a drug trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Movetis

INDUSTRY

Sponsor Role: lead

Responsible Party

Movetis

Principal Investigators

P. Van Eeghem, MD

Role: PRINCIPAL_INVESTIGATOR

Onze Lieve Vrouw Hospital

References

Emmanuel A, Cools M, Vandeplassche L, Kerstens R. Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis. Am J Gastroenterol. 2014 Jun;109(6):887-94. doi: 10.1038/ajg.2014.74. Epub 2014 Apr 15.

Reference Type: DERIVED

PMID: 24732867 (View on PubMed)

Other Identifiers

PRU-INT-2

Identifier Type: -

Identifier Source: org_study_id