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Evaluation of Prucalopride in Male Subjects With Chronic Constipation.

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ClinicalTrials.gov Identifier: NCT01147926
Recruitment Status : Completed
First Posted : June 22, 2010
Results First Posted : September 9, 2014
Last Update Posted : March 25, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Male Subjects With Chronic Constipation
Interventions Drug: Placebo
Drug: Prucalopride
Enrollment 374
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description Placebo matched to Prucalopride tablet orally once daily. Prucalopride 2 milligram (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.
Period Title: Overall Study
Started 187 187
Completed 160 158
Not Completed 27 29
Reason Not Completed
Subject Withdrew Consent             9             10
Adverse Event             7             6
Subject Non-Compliant             5             4
Principal investigator left hospital             1             3
Selection criteria not met             3             1
Lost to Follow-up             0             2
Sponsor's Decision             0             1
Lack of Efficacy             1             0
Too busy, no time for study             1             0
Went on holiday             0             1
Colonoscopy result             0             1
Arm/Group Title PLACEBO PRUCALOPRIDE Total
Hide Arm/Group Description Placebo matched to Prucalopride tablet orally once daily. Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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. Total of all reporting groups
Overall Number of Baseline Participants 186 184 370
Hide Baseline Analysis Population Description
The Safety Population included all subjects randomized into the study and who took at least 1 dose of investigational product (n = 370).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 186 participants 184 participants 370 participants
58.5  (16.28) 58.4  (17.57) 58.5  (16.91)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 184 participants 370 participants
Less than 65 years 115 104 219
Between 65 and 75 years 39 43 82
75 years and above 32 37 69
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 184 participants 370 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
186
 100.0%
184
 100.0%
370
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 184 participants 370 participants
BELGIUM 10 10 20
BULGARIA 9 9 18
CZECH REPUBLIC 15 14 29
DENMARK 21 19 40
FRANCE 20 21 41
GERMANY 11 10 21
NETHERLANDS 5 5 10
POLAND 28 26 54
ROMANIA 57 56 113
UNITED KINGDOM 10 14 24
1.Primary Outcome
Title The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week
Hide Description 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.
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-treat Population (mITT) included all subjects randomized into the study except those excluded due to a major good clinical practice (GCP) breach at one site, who took at least 1 dose of the investigational product.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 181 177
Measure Type: Number
Unit of Measure: percentage of subjects
17.7 37.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PLACEBO, PRUCALOPRIDE
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title 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
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 181 177
Measure Type: Number
Unit of Measure: percentage of subjects
12.2 27.7
3.Secondary Outcome
Title Percentage of Subjects With an Increase of at Least 1 SCBM Per Week
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 181 177
Measure Type: Number
Unit of Measure: percentage of subjects
45.3 53.7
4.Secondary Outcome
Title SCBM Per Week
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 172 170
Mean (Standard Deviation)
Unit of Measure: SCBM/week
1.8  (1.91) 2.6  (2.40)
5.Secondary Outcome
Title Percent SBM With a Consistency of Normal and Hard/Very Hard
Hide Description 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.
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 167 170
Mean (Standard Deviation)
Unit of Measure: percentage of SBM
Normal consistency 50.8  (30.21) 47.5  (31.70)
Hard/Very hard consistency 31.9  (29.86) 26.9  (28.27)
6.Secondary Outcome
Title Percent SCBM With No Straining and Severe/Very Severe Straining
Hide Description Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe)
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 167 170
Mean (Standard Deviation)
Unit of Measure: percentage of SBM
No straining 9.5  (16.23) 9.7  (17.40)
Severe/Very severe straining 23.7  (27.62) 20.6  (27.33)
7.Secondary Outcome
Title Percent SBM With Sensation of Complete Evacuation
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 167 170
Mean (Standard Deviation)
Unit of Measure: percentage of SBM
43.2  (32.90) 46.7  (34.19)
8.Secondary Outcome
Title Time to First SCBM After Investigational Product Intake on Day 1
Hide Description [Not Specified]
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
mITT.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 181 177
Median (95% Confidence Interval)
Unit of Measure: hours
218.9
(143.93 to 291.43)
110.3
(70.8 to 172.77)
9.Secondary Outcome
Title Bisacodyl Tablets Taken Per Week
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 172 170
Mean (Standard Deviation)
Unit of Measure: Tablets/week
1.0  (1.76) 0.6  (1.56)
10.Secondary Outcome
Title Days With Rescue Medication Taken Per Week
Hide Description [Not Specified]
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 172 170
Mean (Standard Deviation)
Unit of Measure: Days/week
0.6  (0.94) 0.3  (0.69)
11.Secondary Outcome
Title Percent of Subjects With an Improvement of ≥ 1 Point on the Patient Assessment of Constipation – Symptom (PAC-SYM) Questionnaire Total Score at Final On Treatment Assessment
Hide Description 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.
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of subjects
30.4 34.9
12.Secondary Outcome
Title Percent of Subjects With an Improvement of ≥ 1 Point on the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Total Score at Final On Treatment Assessment
Hide Description 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.
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of subjects
32.7 40.2
13.Secondary Outcome
Title Percent of Subjects on the Subject Global Evaluation on Severity of Constipation Score Rating Constipation as Severe to Very Severe at Final On-Treatment Assessment
Hide Description Subject was asked to rate the severity of his constipation using a 5-point Likert scale: 0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of subjects
30.4 21.9
14.Secondary Outcome
Title Percent of Subjects on the Subject Global Evaluation on Efficacy of Treatment Score Rating Treatment as Quite a Bit to Extremely Effective at Final On-Treatment Assessment
Time Frame Over 12 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
mITT. Not all subjects in the mITT population had data for this outcome.
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description:
Placebo matched to Prucalopride tablet orally once daily.
Prucalopride 2 mg tablet orally once daily for subjects ≥18 to <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.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of subjects
30.4 46.7
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PLACEBO PRUCALOPRIDE
Hide Arm/Group Description Placebo matched to Prucalopride tablet orally once daily. Prucalopride 2 mg tablet orally once daily for subjects ≥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.
All-Cause Mortality
PLACEBO PRUCALOPRIDE
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
PLACEBO PRUCALOPRIDE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/186 (2.15%)      1/184 (0.54%)    
Cardiac disorders     
ATRIAL FIBRILLATION  0/186 (0.00%)  0 1/184 (0.54%)  1
MYOCARDIAL ISCHAEMIA  1/186 (0.54%)  1 0/184 (0.00%)  0
Injury, poisoning and procedural complications     
LOWER LIMB FRACTURE  1/186 (0.54%)  1 0/184 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
GLOTTIS CARCINOMA  1/186 (0.54%)  1 0/184 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ATELECTASIS  1/186 (0.54%)  1 0/184 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PLACEBO PRUCALOPRIDE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/186 (11.29%)      37/184 (20.11%)    
Gastrointestinal disorders     
ABDOMINAL PAIN  11/186 (5.91%)  12 8/184 (4.35%)  11
DIARRHOEA  3/186 (1.61%)  3 12/184 (6.52%)  16
NAUSEA  4/186 (2.15%)  4 11/184 (5.98%)  12
Nervous system disorders     
HEADACHE  7/186 (3.76%)  8 17/184 (9.24%)  18
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire
Phone: +1 866 842 5335
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01147926     History of Changes
Other Study ID Numbers: SPD555-302
M0001-C302 ( Other Identifier: Movetis )
2009-015719-42 ( EudraCT Number )
First Submitted: June 17, 2010
First Posted: June 22, 2010
Results First Submitted: August 29, 2014
Results First Posted: September 9, 2014
Last Update Posted: March 25, 2015