Evaluation of Prucalopride in Male Subjects With Chronic Constipation.
Condition: Male Subjects With Chronic Constipation
MeSH terms: Constipation
Intervention: Placebo; Prucalopride
Intervention description: Placebo matched to Prucalopride tablet orally once daily.; Prucalopride 2 mg tablet orally once daily for subjects greater than or equal to (≥) 18 to less than (<) 65 years; 1 mg once daily orally for subjects ≥65 years, and in case of insufficient response, increased to 2 mg once daily orally at Week 2 or Week 4.
Intervention MeSH terms: Prucalopride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 374.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Constipation; Male

Summary:

      This is a multi-centre, randomised, parallel-group, double-blind, placebo-controlled phase
      III trial to evaluate the efficacy of prucalopride versus placebo over 12 weeks of treatment
      in male subjects with chronic constipation.

      Furthermore the safety, tolerability, effect on quality of life and effect on symptoms of
      prucalopride will be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is a male out-patient ≥18 years of age (no upper age limit).

          2. Subject has a history of constipation. The subject reports an average of ≤ 2 SBM/week
             that result in a feeling of complete evacuation (SCBM) and one or more of the
             following for at least 6 months before the selection visit:

               1. Very hard (little balls) and/or hard stools for at least a quarter of the stools;

               2. Sensation of incomplete evacuation following for at least a quarter of the
                  stools;

               3. Straining at defecation for at least a quarter of the time. This includes
                  subjects who never have SBMs. The above criteria are only applicable for SBMs,
                  i.e. BMs not preceded within a period of 24 hours by the intake of a laxative
                  agent or by the use of an enema.

          3. Subject agrees to stop his current laxative treatment and is willing to use rescue
             medication according to the rescue rule [Dulcolax® (bisacodyl)/enemas]

          4. Subject's constipation is chronic.

          5. Subject is able and willing to complete the questionnaires (if a validated version in
             the language of the subject is available) and the e-diary.

          6. Subject voluntarily signs the written Informed Consent Form (ICF) in accordance with
             the regional laws/regulations, prior to the first trial-related activity.

          7. Subject is willing to adhere to all trial requirements (amongst others
             colonoscopy/sigmoidoscopy, if required).

        Exclusion Criteria:

          1. Subjects in whom constipation is thought to be drug-induced.

          2. Subjects using any disallowed medication

          3. Subjects suffering from secondary causes of chronic constipation, such as:

             Endocrine disorders, e.g. hypopituitarism, hypothyroidism, hypercalcaemia,
             pseudohypoparathyroidism, pheochromocytoma or glucagon-producing tumours, unless these
             are controlled by appropriate medical therapy. Subjects with insulin-dependent
             diabetes mellitus should always be excluded, also if the subjects are under
             appropriate medical therapy; Metabolic disorders (e.g. porphyria, uraemia,
             hypokalaemia or amyloid neuropathy, unless these are controlled by appropriate medical
             therapy); Neurological disorders (e.g. Parkinson's disease, cerebral tumours,
             cerebrovascular accidents, multiple sclerosis, meningocele, aganglionosis,
             hypoganglionosis, hyperganglionosis, autonomic neuropathy or neuropathy due to
             chemotherapy, spinal cord injury, Chaga's disease, major depression); Surgery.
             Subjects with insulin-dependent diabetes mellitus should always be excluded,
             irrespective of whether the constipation started prior to or after the onset of
             diabetes.

          4. Subjects with a significant history of cancer (i.e. less than a 5-year disease-free
             survival).

          5. Subjects with intestinal perforation or obstruction due to structural or functional
             disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the
             intestinal tract, such as Crohn's disease, and ulcerative colitis and toxic
             megacolon/megarectum. Results of an endoscopy or radiologic bowel evaluation is
             required to rule out polyps, cancer, stricture or other structural or organic disease:

               1. For patients ≤ 50 years: a flexible sigmoidoscopy or colonoscopy after the onset
                  of constipation symptoms and within the previous 5 years;

               2. For patients > 50 years: a flexible sigmoidoscopy /double contrast barium enema
                  or colonoscopy after the onset of constipation symptoms and within the previous 5
                  years.

               3. For subjects, regardless of age, even if results of this test are available
                  within the previous 5 years but if the patient has alarm symptoms such as anemia,
                  weight loss, heme positive stool, or rectal bleeding: a flexible sigmoidoscopy
                  and double contrast barium enema or colonoscopy is needed after the onset of
                  symptoms.

               4. If abnormalities have been detected during the sigmoidoscopy or colonoscopy e.g.,
                  because of polyps, the subject can be included in the trial if the polyps were
                  removed. If clinically indicated, a repeat colonoscopy/sigmoidoscopy needs to be
                  performed at latest within one week after the screening visit. If no barium enema
                  with flexible sigmoidoscopy or a colonoscopic examination has been performed
                  within the period as described above, the assessment is to be scheduled on the
                  screening visit or within the week following screening. When it is clinically
                  indicated that a repeat colonoscopy/sigmoidoscopy is needed to confirm results of
                  a colonoscopy/sigmoidoscopy performed after the screening visit, the subject
                  should be a screen failure.

          6. Subjects with known serious illness: clinically significant cardiac, vascular, liver,
             pulmonary, or psychiatric disorders (as evaluated by the Investigator).

          7. Subjects with any condition that in the opinion of the Investigator would complicate
             or compromise the trial or the well-being of the subject or evidence of clinically
             relevant pathology that could interfere with the trial results or put the subject's
             safety at risk.

          8. Subjects known to have human immunodeficiency virus (HIV) infection or AIDS, hepatitis
             B or hepatitis C.

          9. Subjects with impaired renal function, i.e. serum creatinine concentration >180 μmol/l
             or calculated creatinine clearance ≤30 ml/min, including subjects requiring dialysis.

         10. Subjects with clinically significant abnormalities of haematology, urinalysis, or
             blood chemistry as determined by the Investigator. If the results of the haematology,
             biochemistry or urinalysis tests are not within the laboratory's reference ranges, the
             subject can be included only on the condition that the Investigator judges that the
             deviations are not clinically significant. This should be clearly recorded in the
             electronic Case Report Form (e-CRF).

         11. Subjects with a known history of alcohol or drug abuse in the previous 6 months.

         12. Subjects with lactose intolerance for whom it is expected that low doses of lactose
             can lead to diarrhoea, or a known allergy to ingredients or excipients of the trial
             medication.

         13. Subjects who received an investigational drug in the 30 days preceding the run-in
             period of the trial.

         14. Subjects who previously used prucalopride.