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

Constipation Clinical Trial

— SPD555-401  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01424228
• Other study ID #: M0001-C401
• Secondary ID: 2011-000670-62SP
• Status: Completed
• Phase: Phase 4
• Start date: April 6, 2011
• Est. completion date: December 19, 2012

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: December 19, 2012
• Est. primary completion date: December 19, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Constipation

Intervention

Drug:
• placebo
Placebo matching tablet 2 mg once daily before breakfast for 24 weeks
• 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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St. Luc	Brussel
Belgium	Huisartspraktijk Jaak Mortelmans	Ham
Belgium	Universitaire Ziekenhuizen Leuven	Leuven	Flemish Brabant
Belgium	Centre Hospitalier Universitaire Sart Tilman Liège	Liège
Czechia	Derma Plus s.r.o.	Ceské Budejovice
Czechia	Oblastní nemocnice Kolín, a.s.	Kolin
Czechia	Diagnostika a Lécba Zažívacích Chorob, s.r.o.	Ostrava-Hrabuvka
Czechia	MONSE s.r.o	Praha 1
Czechia	Fakultní Thomayerova nemocnice s poliklinikou	Praha 4 - Krc	Praha
Czechia	Nemocnice Tábor, a.s.	Tabor
Czechia	Orlickoústecká Nemocnice a.s	Ústí nad Orlicí
Hungary	Pannónia Magánorvosi Centrum Kft.	Budapest
Hungary	UNO Medical Trials, Kft.	Budapest
Hungary	Fundamed Háziorvosi Szövetkezet	Érd	Pest
Hungary	Petz Aladár Megyei Oktató Kórház	Gyor	Gyor-moson-sopron
Hungary	Békés Megyei Képviselotestület Pándy Kálmán Kórháza	Gyula	Bekes
Hungary	BAZ Megyei és Egyetemi Oktató Kórház	Miskolc
Hungary	Karolina Kórház Rendelointézet	Mosonmagyaróvar	Gyor-moson-sopron
Hungary	Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinika	Szeged	Csongrad
Hungary	Fejér Megyei Szent György Kórház	Székesfehérvár	Pejer
Hungary	Clinfan Kft. SMO	Szekszárd
Hungary	Dr. Bugyi István Kórház	Szentes	Csongrad
Hungary	CRU Hungary Kft.	Szikszó
Hungary	Bíró Praxis Kft.	Úrhida
Hungary	Jávorszky Ödön Városi Kórház	Vác
Italy	Azienda Ospedale San Martino	Genova
Italy	Policlinico Universitario	Padova
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	Azienda Policlinico Umberto I di Roma	Roma
Italy	Policlinico Universitario Campus Biomedico	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Poland	Centrum Medyczne sw. Lukasza Sp. z o.o.	Czestochowa	Slaskie
Poland	Krakowskie Centrum Medyczne NZOZ	Krakow	Malopolskie
Poland	Szpital Wojewódzki w Opolu	Opole	Opolskie
Poland	Endoskopia Sp. z o.o.	Sopot	Pomorskie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "SONOMED"	Szczecin	Zachodniopomorskie
Poland	Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ	Warszawa	Mazowieckie
Romania	Centrul Medical Sana	Bucharest	Bucuresti
Romania	SC Cabinet Medical Dr. Blaj Stefan SRL	Bucharest	Sector 5
Romania	Spitalul Militar Central Bucuresti	Bucharest	Bucuresti
Romania	Endocenter Medicina Integrativa SRL	Bucuresti
Romania	Spitalul Clinic Judetean Cluj,Clinica Medicala I	Cluj-Napoca	Cluj
Romania	Biomed Plus SRL	Craiova	Dolj
Romania	Gastromedica SRL	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu
Romania	CMI de Gastroenterologie Dobru Daniela	Targu-Mures
Romania	Centrul Medical Tuculanu SRL	Timisoara	Timis
Romania	Policlinic Algomed SRL	Timisoara
Slovakia	Lama Medical Care s.r.o., Gastroentero-hepatologicke centrum Thalion	Bratislava
Slovakia	Gastroenterologická ambulancia	Košice
Slovakia	PIGEAS s.r.o.	Martin
Slovakia	Radvanská lekáren, spol. s r.o.,	Nitra
Slovakia	Gastro I.s.r.o.	Prešov
Slovakia	GEA s.r.o Gastroenterologicka ambulancia	Trnava
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario Nuestra Señora de Valme	Sevilla
Sweden	Sahlgrenska Universitetsjukhuset	Göteborg	Vastra Gotaland
Sweden	Aleris Specialistvård Sabbatsberg	Stockholm
Sweden	Karolinska University Hospital Solna	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

Belgium,  Czechia,  Hungary,  Italy,  Poland,  Romania,  Slovakia,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Subjects With an Increase of =1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks		Over 24 week treatment period
Secondary	Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks		Over 24 week treatment period
Secondary	Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks		Baseline and Over 24 week treatment period
Secondary	Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week		Over 24 week treatment period
Secondary	Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period		Over 24 week treatment period
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks		Baseline and Over 24 week treatment period
Secondary	Time to First SCBM After Investigational Product Intake on Day 1 and Day 28		Day 1 and 28
Secondary	Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks		Baseline and Over 24 week treatment period
Secondary	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
Secondary	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
Secondary	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
Secondary	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