Evaluation of Long-term Prucalopride Treatment With Chronic Constipation in Subjects Aged ≥ 18 Years (SPD555-401)

A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Quality of Life, Safety and Tolerability of Long-term Treatment (24 Weeks) With Prucalopride in Subjects Aged ≥18 Years With Chronic Constipation

The purpose of this trial is to evaluate the long-term (24 weeks) efficacy of prucalopride versus placebo in subjects aged 18 years and older with chronic constipation.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: placebo; Drug: prucalopride

Detailed Description

In this phase IV trial a total of 340 subjects (170 subjects per treatment group), with chronic constipation, are planned to be randomly assigned to double-blind treatment.

The trial duration for a subject can be 26 to 28 weeks in total, including a 2- to 4-week run-in phase followed by a 24-week double-blind treatment phase. The patient will complete an e-diary.

Adult subjects (≥18 to <65 years of age) will take 2 mg prucalopride or matching placebo throughout the entire 24-week treatment period. Elderly subjects (≥65 years of age) will start at a dose of 1 mg prucalopride or matching placebo. In case of insufficient response the daily dose has to be increased to 2 mg (i.e. changed to 2 mg prucalopride or matching placebo).

• Study Type: Interventional
• Enrollment (Actual): 364
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1200
    • Cliniques Universitaires St. Luc
  • Ham, Belgium, 3945
    • Huisartspraktijk Jaak Mortelmans
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire Sart Tilman Liège
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven
• Czechia
  • Ceské Budejovice, Czechia, 370 01
    • Derma Plus s.r.o.
  • Kolin, Czechia, 280 20
    • Oblastni nemocnice Kolin, a.s.
  • Ostrava-Hrabuvka, Czechia, 700 30
    • Diagnostika a Lécba Zažívacích Chorob, s.r.o.
  • Praha 1, Czechia, 118 33
    • MONSE s.r.o
  • Tabor, Czechia, 390 03
    • Nemocnice Tabor, a.s.
  • Ústí nad Orlicí, Czechia, 562 18
    • Orlickoústecká Nemocnice a.s
  • Praha
    • Praha 4 - Krc, Praha, Czechia, 140 59
      • Fakultni Thomayerova nemocnice s poliklinikou
• Hungary
  • Budapest, Hungary, 1136
    • Pannonia Maganorvosi Centrum Kft.
  • Budapest, Hungary, 1135
    • UNO Medical Trials, Kft.
  • Miskolc, Hungary, 3526
    • BAZ Megyei és Egyetemi Oktató Kórház
  • Szekszárd, Hungary, 7100
    • Clinfan Kft. SMO
  • Szikszó, Hungary, 3800
    • CRU Hungary Kft.
  • Vác, Hungary, 2600
    • Jávorszky Ödön Városi Kórház
  • Úrhida, Hungary, 8142
    • Bíró Praxis Kft.
  • Bekes
    • Gyula, Bekes, Hungary, 5700
      • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinika
    • Szentes, Csongrad, Hungary, 6600
      • Dr. Bugyi Istvan Korhaz
  • Gyor-moson-sopron
    • Gyor, Gyor-moson-sopron, Hungary, 9024
      • Petz Aladar Megyei Oktato Korhaz
    • Mosonmagyaróvar, Gyor-moson-sopron, Hungary, 9200
      • Karolina Korhaz Rendelointezet
  • Pejer
    • Székesfehérvár, Pejer, Hungary, 8000
      • Fejer Megyei Szent Gyorgy Korhaz
  • Pest
    • Érd, Pest, Hungary, 2030
      • Fundamed Háziorvosi Szövetkezet
• Italy
  • Genova, Italy, 16132
    • Azienda Ospedale San Martino
  • Padova, Italy, 35128
    • Policlinico Universitario
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico S. Matteo
  • Roma, Italy, 00161
    • Azienda Policlinico Umberto I di Roma
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Biomedico
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas
• Poland
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-501
      • Krakowskie Centrum Medyczne NZOZ
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-653
      • Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ
  • Opolskie
    • Opole, Opolskie, Poland, 45-061
      • Szpital Wojewodzki w Opolu
  • Pomorskie
    • Sopot, Pomorskie, Poland, 81-756
      • ENDOSKOPIA Sp. z o.o.
  • Slaskie
    • Czestochowa, Slaskie, Poland, 42-202
      • Centrum Medyczne sw. Lukasza Sp. z o.o.
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-361
      • Niepubliczny Zaklad Opieki Zdrowotnej "SONOMED"
• Romania
  • Bucuresti, Romania, 021978
    • Endocenter Medicina Integrativa SRL
  • Iasi, Romania, 700506
    • Gastromedica Srl
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean de Urgenta Sibiu
  • Targu-Mures, Romania, 540103
    • CMI de Gastroenterologie Dobru Daniela
  • Timisoara, Romania, 300002
    • Policlinic Algomed SRL
  • Bucuresti
    • Bucharest, Bucuresti, Romania, 010825
      • Spitalul Militar Central Bucuresti
    • Bucharest, Bucuresti, Romania, 011025
      • Centrul Medical Sana
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400006
      • Spitalul Clinic Judetean Cluj,Clinica Medicala I
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Biomed Plus SRL
  • Sector 5
    • Bucharest, Sector 5, Romania, 040101
      • SC Cabinet Medical Dr. Blaj Stefan SRL
  • Timis
    • Timisoara, Timis, Romania, 300158
      • Centrul Medical Tuculanu SRL
• Slovakia
  • Bratislava, Slovakia, 811 07
    • Lama Medical Care s.r.o., Gastroentero-hepatologicke centrum Thalion
  • Košice, Slovakia, 040 01
    • Gastroenterologická ambulancia
  • Martin, Slovakia, 03601
    • Pigeas s.r.o.
  • Nitra, Slovakia, 950 01
    • Radvanská lekáren, spol. s r.o.,
  • Prešov, Slovakia, 08001
    • Gastro I.s.r.o.
  • Trnava, Slovakia, 91701
    • GEA s.r.o Gastroenterologicka ambulancia
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Sevilla, Spain, 41014
    • Hospital Universitario Nuestra Señora de Valme
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Parc Tauli
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital Solna
  • Stockholm, Sweden, 113 82
    • Aleris Specialistvård Sabbatsberg
  • Vastra Gotaland
    • Göteborg, Vastra Gotaland, Sweden, 413 45
      • Sahlgrenska Universitetsjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is a male or non-pregnant, non-breastfeeding female 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).
3. Subject agrees to stop his/her current laxative treatment and is willing to use rescue medication according to the rescue rule [bisacodyl/enemas].

Exclusion Criteria:

1. Subjects in whom constipation is thought to be drug-induced
2. Subjects using any disallowed medication.
3. Subjects who previously used prucalopride.
4. Subjects suffering from secondary causes of chronic constipation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo 2 mg tablet once daily before breakfast	Drug: placebo; Placebo matching tablet 2 mg once daily before breakfast for 24 weeks
ACTIVE_COMPARATOR: prucalopride; Prucalopride 2 mg once daily before breakfast	Drug: prucalopride; Prucalopride 2 mg daily before breakfast 1 mg for subjects >65 years; in case of insufficient response 2 mg at week 2 or week 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period	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 24 week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With an Increase of ≥1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks		Over 24 week treatment period
Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks		Over 24 week treatment period
Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks		Baseline and Over 24 week treatment period
Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week		Over 24 week treatment period
Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period		Over 24 week treatment period
Change From Baseline in Average Consistency Per SCBM at Up to 24 Weeks	Consistency measured using the 7-point Bristol scale where 1-2 indicate constipation (=hard/very hard), 3-4 are ideal stools (=normal), and 5-7 tending toward diarrhea.	Baseline and Over 24 week treatment period
Change From Baseline in Percent SCBM With a Consistency of Normal and Hard/Very Hard at Up to 24 Weeks		Baseline and Over 24 week treatment period
Change From Baseline in Straining Per SCBM at Up to 24 Weeks	Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe)	Baseline and Over 24 week treatment period
Change From Baseline in Percent SCBM With No Straining and Severe/Very Severe Straining at Up to 24 Weeks		Baseline and Over 24 week treatment period
Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks		Baseline and Over 24 week treatment period
Time to First SCBM After Investigational Product Intake on Day 1 and Day 28		Day 1 and 28
Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks		Baseline and Over 24 week treatment period
Change From Baseline in the Number of Days With Rescue Medication Taken Per Week at Up to 24 Weeks	Rescue medications include laxatives and enemas.	Baseline and Over 24 week treatment period
Change From Baseline in the Patient Assessment of Constipation - Symptom (PAC-SYM) Questionnaire Score at Up to the Final On Treatment Assessment Value	The PAC-SYM is a validated 12-item questionnaire for the evaluation of severity of symptoms of constipation in subjects with constipation. Items are rated on a 5-point Likert scale: 0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe. Total score ranges from 0 to 48. Lower scores indicate improvement in symptoms. A 1-point improvement in PAC-SYM total score was considered clinically meaningful.	Baseline and Over 24 week treatment period
Change From Baseline in the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score at Up to the Final On Treatment Assessment Value	The PAC-QOL is a validated 28-item questionnaire for the evaluation of quality of life in subjects with constipation. Items are rated on a 5-point Likert scale: 0=not at all/none of the time, 1=a little bit/a little bit of the time, 2=moderately/some of the time, 3=quite a bit/most of the time, 4=extremely/all of the time. Total score ranges from 0-112. Lower scores indicate improvement in symptoms. A 1-point improvement in PAC-QOL total score was considered clinically meaningful.	Baseline and Over 24 week treatment period
Change From Baseline in the Short Form-36 Health Survey (SF-36) Score at Up to the Final On Treatment Assessment Value	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Total score ranges from 0 (lowest level of health) - 100 (highest level of health) on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). Higher scores are associated with better quality of life.	Baseline and Over 24 week treatment period

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.
• Piessevaux H, Corazziari E, Rey E, Simren M, Wiechowska-Kozlowska A, Kerstens R, Cools M, Barrett K, Levine A. A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride. Neurogastroenterol Motil. 2015 Jun;27(6):805-15. doi: 10.1111/nmo.12553. Epub 2015 Mar 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 6, 2011
• Primary Completion (ACTUAL): December 19, 2012
• Study Completion (ACTUAL): December 19, 2012

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (ESTIMATE): August 26, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Constipation; Long term; Digestive signs and symptoms
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: M0001-C401; 2011-000670-62 (EUDRACT_NUMBER); SPD555-401 (OTHER: Shire)