Evaluation of Prucalopride in Male Subjects With Chronic Constipation.

NCT01147926 | Completed Phase 3 Results

• 3 other identifiers: SPD555-302M0001-C3022009-015719-42
• Study Type: interventional
• Target: 374
• Locations: 10 countries
• Sites: 73

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.

Conditions

Male Subjects With Chronic Constipation

Keywords

Constipation; Male

Outcome Measures

Primary Outcomes (1)

• The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week

  Spontaneous Bowel Movements defined as a bowel movement that is not preceded within a period of 24 hours by the intake of a laxative agent or by the use of an enema.

  Over 12 week treatment period

Secondary Outcomes (13)

• Percentage of Subjects With an Average Weekly Frequency of at Least 3 SCBM Per Week and an Increase of ≥ 1 SCBM Per Week for ≥ 75% of the 12-week Treatment Period and ≥ 75% of the Last Third of the 12-week Treatment Period

  Over 12 week treatment period

• Percentage of Subjects With an Increase of at Least 1 SCBM Per Week

  Over 12 week treatment period

• SCBM Per Week

  Over 12 week treatment period

• Percent SBM With a Consistency of Normal and Hard/Very Hard

  Over 12 week treatment period

• Percent SCBM With No Straining and Severe/Very Severe Straining

  Over 12 week treatment period

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Prucalopride

ACTIVE COMPARATOR

1 milligram (mg) or 2 mg

Drug: Prucalopride

Interventions

Placebo DRUG

Placebo matched to Prucalopride tablet orally once daily.

Placebo

Prucalopride 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.

Prucalopride

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is a male out-patient ≥18 years of age (no upper age limit).
• 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:
• Very hard (little balls) and/or hard stools for at least a quarter of the stools;
• Sensation of incomplete evacuation following for at least a quarter of the stools;
• 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.
• Subject agrees to stop his current laxative treatment and is willing to use rescue medication according to the rescue rule \[Dulcolax® (bisacodyl)/enemas\]
• Subject's constipation is chronic.
• 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.
• Subject voluntarily signs the written Informed Consent Form (ICF) in accordance with the regional laws/regulations, prior to the first trial-related activity.
• Subject is willing to adhere to all trial requirements (amongst others colonoscopy/sigmoidoscopy, if required).

You may not qualify if:

• Subjects in whom constipation is thought to be drug-induced.
• Subjects using any disallowed medication
• 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.
• Subjects with a significant history of cancer (i.e. less than a 5-year disease-free survival).
• 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:
• For patients ≤ 50 years: a flexible sigmoidoscopy or colonoscopy after the onset of constipation symptoms and within the previous 5 years;
• 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.
• 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.
• 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.
• Subjects with known serious illness: clinically significant cardiac, vascular, liver, pulmonary, or psychiatric disorders (as evaluated by the Investigator).
• 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.
• Subjects known to have human immunodeficiency virus (HIV) infection or AIDS, hepatitis B or hepatitis C.
• Subjects with impaired renal function, i.e. serum creatinine concentration \>180 μmol/l or calculated creatinine clearance ≤30 ml/min, including subjects requiring dialysis.
• 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).

Sponsors & Collaborators

• Shire: lead

Study Sites (73)

Gastro-Kliniek cvba

Antwerp, 2018, Belgium

Location

Cliniques Universitaires St Luc

Brussels, 1200, Belgium

Location

GP / Huisartsenpraktijk De Regenboog

Deurne, 2100, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

Private Practice

Wetteren, 9230, Belgium

Location

4 MHAT

Sofia, 1000, Bulgaria

Location

CCBR Czech Republic Brno

Brno, 60200, Czechia

Location

KKN a.s.

Karlovy Vary, 36001, Czechia

Location

CCBR Czech Republic Pardubice

Pardubice, 530 02, Czechia

Location

Universtiy Hospital Kralovske Vinhorady

Prague, 100 34, Czechia

Location

MONSE s.r.o.

Prague, 118 33, Czechia

Location

Hospital Slany

Slaný, 274 01, Czechia

Location

Orlickoustecka nemocnice

Ústí nad Orlicí, 562 01, Czechia

Location

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

Zlín, 762 75, Czechia

Location

Krajska Nemocnice T. Bati a.s.

Zlín, 762 75, Czechia

Location

CCBR DK Aalborg

Aalborg, 9000, Denmark

Location

CCBR DK Ballerup

Ballerup Municipality, 2750, Denmark

Location

CCBR DK Vejle

Vejle, 7100, Denmark

Location

CHU - Hopital Nord, service gastro-enterologie et hepatologie

Amiens, 80054, France

Location

ARK Clinical Research (Jean XXIII)

Angers, 49000, France

Location

ARK Clinical Research (Proust)

Angers, 49000, France

Location

ARK Clinical Research - Chanzy

Angers, 49000, France

Location

ARK Clinical Research

Avrillé, 49000, France

Location

Hopital Avicenne, Centre d'exploitation fonctionnelle et reducation digestive

Bobigny, 93009, France

Location

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

Dijon, 21079, France

Location

ARK Clinical Research

Le Plessis-Grammoire, 49124, France

Location

Hôpital Edouard Herriot

Lyon, 69437, France

Location

Hopital Archet 2- service gastro-enterologie et hepatologie

Nice, 06002, France

Location

Hôpital Pontchaillou - Service des Maladies de l'Appareil Digestif

Rennes, 35000, France

Location

Cabinet Médical

Thouars, France

Location

ARK Clinical Research

Vendôme, 41100, France

Location

emovis GmbH

Berlin, 10629, Germany

Location

Gastroenterologie und Hepatologie am Johannisplatz

Leipzig, 04103, Germany

Location

Fachartzpraxis für Innere Medizin

Wiesbaden, 65285, Germany

Location

Meander Medisch Centrum

Amersfoort, 3818 ES, Netherlands

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

PT&R / PreCare Trial & Recruitment

Beek, 6191JW, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, 6716 RP, Netherlands

Location

Maastricht Universitair medisch Centrum

Maastricht, 6229 HX, Netherlands

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

Ikazia Ziekenhuis

Rotterdam, 3083 AN, Netherlands

Location

Gabinet Lekarski Janusz Rudziński

Bydgoszcz, 85-681, Poland

Location

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

Lublin, 20-950, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Endoskopia Sp. z o.o.

Sopot, 81-756, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Chirurgii Ogólnej i Gastroenterologii

Torun, 87-100, Poland

Location

Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ

Warsaw, 02-653, Poland

Location

NZOZ Vivamed

Warsaw, 03-580, Poland

Location

CMI Dr. Lenghel Augustin

Oradea, Bihor County, 410163, Romania

Location

Centrul Medical Valahia SRL

Ploieşti, Prahova, 100410, Romania

Location

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

Bucharest, Sector 1, 010825, Romania

Location

SC Quantum Medical Center SRL

Bucharest, Sector 1, 011426, Romania

Location

Endocenter Medicina Integrativa SRL

Bucharest, Sector 2, 021978, Romania

Location

SC Mediclass Sananova SRL

Bucharest, Sector 5, 050524, Romania

Location

SC Cabinet Medical Dr. Blaj Stefan SRL

Bucharest, Sector 5, 40101, Romania

Location

Centrul Medical Humanitas

Bucharest, Sector 6, 062272, Romania

Location

Centrul Medical Tuculanu SRL

Timișoara, Timiș County, 300158, Romania

Location

Centrul Medical Sana

Bucharest, 11025, Romania

Location

Spitalul Clinic Judetean Cluj,Clinica Medicala I

Cluj-Napoca, 400006, Romania

Location

Gastromedica SRL

Iași, 700506, Romania

Location

Cabinet Medical Dr. Lokos Barna-Csaba

Miercurea-Ciuc, 530174, Romania

Location

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, 550245, Romania

Location

CMI de Gastroenterologie Dobru Daniela

Târgu Mureş, 540130, Romania

Location

Policlinic Algomed SRL

Timișoara, 300002, Romania

Location

Oldfield Surgery

Bath, BA2 3HT, United Kingdom

Location

Avondale Surgery

Chesterfield, S40 4TE, United Kingdom

Location

University Hospital & Warwickshire -

Coventry, CV2 2DX, United Kingdom

Location

County Durham & Darlington NHS Foundation Trust

Durham, DH1 5GA, United Kingdom

Location

Burbage Surgery

Hinckley, LE10 2SE, United Kingdom

Location

Townhead Research

Irvine, KA12 0AY, United Kingdom

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Sherbourne Medical Centre

Royal Leamington Spa, CV32 4RA, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 39664231 DERIVED

• 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.

  PMID: 34585675 DERIVED

• 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.

  PMID: 25869393 DERIVED

MeSH Terms

Conditions

Constipation

Interventions

prucalopride

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: September 23, 2010
• Primary Completion: October 25, 2013
• Study Completion: October 25, 2013
• Last Updated: June 10, 2021
• Results First Posted: September 9, 2014

Record last verified: 2021-05

Locations

DE (3); BE (6); BU (1); PL (7); CZ (9); DK (3); FR (13); NL (7); GB (8); RO (16)