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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01424228
First received: August 25, 2011
Last updated: August 13, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Constipation
Drug: placebo
Drug: prucalopride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period [ Time Frame: Over 24 week treatment period ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Subjects With an Increase of ≥1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks [ Time Frame: Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks [ Time Frame: Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week [ Time Frame: Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period [ Time Frame: Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Change From Baseline in Average Consistency Per SCBM at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Percent SCBM With a Consistency of Normal and Hard/Very Hard at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Change From Baseline in Straining Per SCBM at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe)

  • Change From Baseline in Percent SCBM With No Straining and Severe/Very Severe Straining at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Time to First SCBM After Investigational Product Intake on Day 1 and Day 28 [ Time Frame: Day 1 and 28 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
  • Change From Baseline in the Number of Days With Rescue Medication Taken Per Week at Up to 24 Weeks [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    Rescue medications include laxatives and enemas.

  • Change From Baseline in the Patient Assessment of Constipation - Symptom (PAC-SYM) Questionnaire Score at Up to the Final On Treatment Assessment Value [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score at Up to the Final On Treatment Assessment Value [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Short Form-36 Health Survey (SF-36) Score at Up to the Final On Treatment Assessment Value [ Time Frame: Baseline and Over 24 week treatment period ] [ Designated as safety issue: No ]
    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.


Enrollment: 364
Study Start Date: June 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424228

  Show 60 Study Locations
Sponsors and Collaborators
Shire
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01424228     History of Changes
Other Study ID Numbers: M0001-C401, 2011-000670-62
Study First Received: August 25, 2011
Results First Received: November 11, 2013
Last Updated: August 13, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Poland: CEBK
Romania: National Medicines Agency
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency

Keywords provided by Shire:
Long term
Constipation
Digestive signs and symptoms

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on August 26, 2014