Evaluation of Prucalopride in Male Subjects With Chronic Constipation.

NCT ID: NCT01147926

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 374 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-23
• Study Completion Date: 2013-10-25

Brief 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.

Detailed Description

In this phase III trial subjects will be screened and enter a 2-week run-in period (or a 3-week run-in period if the subject is using agents that influence bowel habit) during which the presence of constipation will be confirmed [the subject will complete an electronic daily diary (e-diary)]. At the start of run-in, all existing laxative medication will be withdrawn and subjects will be instructed not to change their diet or lifestyle during the trial. Subjects will be allowed to take a laxative [Dulcolax (bisacodyl)] as rescue medication during the trial, but only if they have not had a bowel movement (BM) for 3 or more consecutive days. An enema can only be used after unsuccessful use of Dulcolax (bisacodyl). No Dulcolax (bisacodyl) should be taken or enemas used between 48 hours before and 48 hours after the first intake of study medication.

After the run-in subjects will be randomly assigned to placebo or prucalopride in an equal ratio (1:1) if the subject fulfils the constipation criteria for inclusion. Randomisation will be stratified by country and by the average number of complete bowel movements (CBM) during run-in: 0 CBM/week and > 0 CBM/week.

Adult subjects (i.e. subjects ≥18 to <65 years of age) will take 2 mg prucalopride or matching placebo once daily before breakfast during the entire 12-week treatment period. Elderly subjects (i.e. subjects ≥65 years of age) will start at a dose of 1 mg prucalopride or matching placebo once daily before breakfast. In case of insufficient response, defined as an average of <3 spontaneous complete bowel movements (SCBM)/week during the preceding 2 weeks of treatment (i.e. since the previous visit) at Week 2 or Week 4, the daily dose has to be increased to 2 mg (or matching placebo). Once the dose is increased to 2 mg once daily the subject will stay on this dose for the remainder of the trial. After Week 4 (Visit 4) no changes in dose are allowed anymore.

Conditions

Male Subjects With Chronic Constipation

Study Design

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

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matched to Prucalopride tablet orally once daily.

Prucalopride

1 milligram (mg) or 2 mg

Group Type: ACTIVE_COMPARATOR

Prucalopride

Intervention Type: DRUG

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.

Interventions

Placebo

Placebo matched to Prucalopride tablet orally once daily.

Intervention Type: DRUG

Prucalopride

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 Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Gastro-Kliniek cvba

Antwerp, , Belgium

Cliniques Universitaires St Luc

Brussels, , Belgium

GP / Huisartsenpraktijk De Regenboog

Deurne, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

CHU Sart Tilman

Liège, , Belgium

Private Practice

Wetteren, , Belgium

4 MHAT

Sofia, , Bulgaria

CCBR Czech Republic Brno

Brno, , Czechia

KKN a.s.

Karlovy Vary, , Czechia

CCBR Czech Republic Pardubice

Pardubice, , Czechia

Universtiy Hospital Kralovske Vinhorady

Prague, , Czechia

MONSE s.r.o.

Prague, , Czechia

Hospital Slany

Slaný, , Czechia

Orlickoustecka nemocnice

Ústí nad Orlicí, , Czechia

Krajska Nemocnice T. Bati a.s., Interni oddeleni - klinika IPVZ; Nemocnicni Lekarna

Zlín, , Czechia

Krajska Nemocnice T. Bati a.s.

Zlín, , Czechia

CCBR DK Aalborg

Aalborg, , Denmark

CCBR DK Ballerup

Ballerup Municipality, , Denmark

CCBR DK Vejle

Vejle, , Denmark

CHU - Hopital Nord, service gastro-enterologie et hepatologie

Amiens, , France

ARK Clinical Research (Jean XXIII)

Angers, , France

ARK Clinical Research (Proust)

Angers, , France

ARK Clinical Research - Chanzy

Angers, , France

ARK Clinical Research

Avrillé, , France

Hopital Avicenne, Centre d'exploitation fonctionnelle et reducation digestive

Bobigny, , France

Service de Gastroenterologie & INSERM CIC-P 803 - CHU de Dijon

Dijon, , France

ARK Clinical Research

Le Plessis-Grammoire, , France

Hôpital Edouard Herriot

Lyon, , France

Hopital Archet 2- service gastro-enterologie et hepatologie

Nice, , France

Hôpital Pontchaillou - Service des Maladies de l'Appareil Digestif

Rennes, , France

Cabinet Médical

Thouars, , France

ARK Clinical Research

Vendôme, , France

emovis GmbH

Berlin, , Germany

Gastroenterologie und Hepatologie am Johannisplatz

Leipzig, , Germany

Fachartzpraxis für Innere Medizin

Wiesbaden, , Germany

Meander Medisch Centrum

Amersfoort, , Netherlands

VU Medisch Centrum

Amsterdam, , Netherlands

PT&R / PreCare Trial & Recruitment

Beek, , Netherlands

Ziekenhuis Gelderse Vallei

Ede, , Netherlands

Maastricht Universitair medisch Centrum

Maastricht, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Gabinet Lekarski Janusz Rudziński

Bydgoszcz, , Poland

Instytut Medycyny Wsi im. Witolda Chodźki - Zaklad Endoskopowych Badań Kliniczncyh

Lublin, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, , Poland

Endoskopia Sp. z o.o.

Sopot, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Chirurgii Ogólnej i Gastroenterologii

Torun, , Poland

Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ

Warsaw, , Poland

NZOZ Vivamed

Warsaw, , Poland

CMI Dr. Lenghel Augustin

Oradea, Bihor County, Romania

Centrul Medical Valahia SRL

Ploieşti, Prahova, Romania

Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"

Bucharest, Sector 1, Romania

SC Quantum Medical Center SRL

Bucharest, Sector 1, Romania

Endocenter Medicina Integrativa SRL

Bucharest, Sector 2, Romania

SC Mediclass Sananova SRL

Bucharest, Sector 5, Romania

SC Cabinet Medical Dr. Blaj Stefan SRL

Bucharest, Sector 5, Romania

Centrul Medical Humanitas

Bucharest, Sector 6, Romania

Centrul Medical Tuculanu SRL

Timișoara, Timiș County, Romania

Centrul Medical Sana

Bucharest, , Romania

Spitalul Clinic Judetean Cluj,Clinica Medicala I

Cluj-Napoca, , Romania

Gastromedica SRL

Iași, , Romania

Cabinet Medical Dr. Lokos Barna-Csaba

Miercurea-Ciuc, , Romania

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, , Romania

CMI de Gastroenterologie Dobru Daniela

Târgu Mureş, , Romania

Policlinic Algomed SRL

Timișoara, , Romania

Oldfield Surgery

Bath, , United Kingdom

Avondale Surgery

Chesterfield, , United Kingdom

University Hospital & Warwickshire -

Coventry, , United Kingdom

County Durham & Darlington NHS Foundation Trust

Durham, , United Kingdom

Burbage Surgery

Hinckley, , United Kingdom

Townhead Research

Irvine, , United Kingdom

Wythenshawe Hospital

Manchester, , United Kingdom

Sherbourne Medical Centre

Royal Leamington Spa, , United Kingdom

Countries

Belgium; Bulgaria; Czechia; Denmark; France; Germany; Netherlands; Poland; Romania; United Kingdom

References

Lembo A, Staller K, Boules M, Feuerstadt P, Spalding W, Gabriel A, Youssef A, Xie Y, Terreri B, Cash BD. Efficacy and safety of prucalopride in patients with chronic idiopathic constipation stratified by age, body mass index, and renal function: a post hoc analysis of phase III and IV, randomized, placebo-controlled clinical studies. Therap Adv Gastroenterol. 2024 Dec 10;17:17562848241299731. doi: 10.1177/17562848241299731. eCollection 2024.

Reference Type: DERIVED

PMID: 39664231 (View on PubMed)

Staller K, Hinson J, Kerstens R, Spalding W, Lembo A. Efficacy of Prucalopride for Chronic Idiopathic Constipation: An Analysis of Participants With Moderate to Very Severe Abdominal Bloating. Am J Gastroenterol. 2022 Jan 1;117(1):184-188. doi: 10.14309/ajg.0000000000001521.

Reference Type: DERIVED

PMID: 34585675 (View on PubMed)

Yiannakou Y, Piessevaux H, Bouchoucha M, Schiefke I, Filip R, Gabalec L, Dina I, Stephenson D, Kerstens R, Etherson K, Levine A. A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. Am J Gastroenterol. 2015 May;110(5):741-8. doi: 10.1038/ajg.2015.115. Epub 2015 Apr 14.

Reference Type: DERIVED

PMID: 25869393 (View on PubMed)

Other Identifiers

M0001-C302

Identifier Type: OTHER

Identifier Source: secondary_id

2009-015719-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD555-302

Identifier Type: -

Identifier Source: org_study_id