NCT01147926

Evaluation of Prucalopride in Male Subjects With Chronic Constipation.

Completed Phase 3 Results posted Last updated 10 June 2021

What this trial tests

Phase 3 trial testing Placebo in Male Subjects With Chronic Constipation in 374 participants. Completed in 25 October 2013.

Timeline

23 September 2010

Primary endpoint
25 October 2013

25 October 2013

Quick facts

Lead sponsor	Shire
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	374
Start date	23 September 2010
Primary completion	25 October 2013
Estimated completion	25 October 2013
Sites	73 locations across Denmark, France, Netherlands, Belgium, United Kingdom, Germany, Poland, Romania

Drugs / interventions tested

• Placebo
• Prucalopride — full drug profile →

Conditions studied

• Male Subjects With Chronic Constipation — all drugs for Male Subjects With Chronic Constipation →

Sponsor

Shire — full company profile →

Who can join

18 and older, male only, with Male Subjects With Chronic Constipation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Primary · Over 12 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.

Group	Value	95% CI
PLACEBO	17.7
PRUCALOPRIDE	37.9

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 Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	12.2
PRUCALOPRIDE	27.7

Percentage of Subjects With an Increase of at Least 1 SCBM Per Week Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	45.3
PRUCALOPRIDE	53.7

SCBM Per Week Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	1.8	± 1.91
PRUCALOPRIDE	2.6	± 2.40

Percent SBM With a Consistency of Normal and Hard/Very Hard Secondary · Over 12 week treatment period

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.

Normal consistency

Group	Value	95% CI
PLACEBO	50.8	± 30.21
PRUCALOPRIDE	47.5	± 31.70

Hard/Very hard consistency

Group	Value	95% CI
PLACEBO	31.9	± 29.86
PRUCALOPRIDE	26.9	± 28.27

Percent SCBM With No Straining and Severe/Very Severe Straining Secondary · Over 12 week treatment period

Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe)

No straining

Group	Value	95% CI
PLACEBO	9.5	± 16.23
PRUCALOPRIDE	9.7	± 17.40

Severe/Very severe straining

Group	Value	95% CI
PLACEBO	23.7	± 27.62
PRUCALOPRIDE	20.6	± 27.33

Percent SBM With Sensation of Complete Evacuation Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	43.2	± 32.90
PRUCALOPRIDE	46.7	± 34.19

Time to First SCBM After Investigational Product Intake on Day 1 Secondary · Day 1

Group	Value	95% CI
PLACEBO	218.9	143.93 – 291.43
PRUCALOPRIDE	110.3	70.8 – 172.77

Bisacodyl Tablets Taken Per Week Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	1.0	± 1.76
PRUCALOPRIDE	0.6	± 1.56

Days With Rescue Medication Taken Per Week Secondary · Over 12 week treatment period

Group	Value	95% CI
PLACEBO	0.6	± 0.94
PRUCALOPRIDE	0.3	± 0.69

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 Secondary · Over 12 week treatment period

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.

Group	Value	95% CI
PLACEBO	30.4
PRUCALOPRIDE	34.9

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 Secondary · Over 12 week treatment period

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.

Group	Value	95% CI
PLACEBO	32.7
PRUCALOPRIDE	40.2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PLACEBO

Serious: 4/186 (2%)

Deaths: —

PRUCALOPRIDE

Serious: 1/184 (1%)

Deaths: —

Serious adverse events (5 terms)

Reaction	System	PLACEBO	PRUCALOPRIDE
ATRIAL FIBRILLATION	Cardiac disorders	—	—
MYOCARDIAL ISCHAEMIA	Cardiac disorders	—	—
LOWER LIMB FRACTURE	Injury, poisoning and procedural complications	—	—
GLOTTIS CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
ATELECTASIS	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	PLACEBO	PRUCALOPRIDE
HEADACHE	Nervous system disorders	—	—
DIARRHOEA	Gastrointestinal disorders	—	—
ABDOMINAL PAIN	Gastrointestinal disorders	—	—
NAUSEA	Gastrointestinal disorders	—	—

Most-reported serious reactions: ATRIAL FIBRILLATION, MYOCARDIAL ISCHAEMIA, LOWER LIMB FRACTURE, GLOTTIS CARCINOMA, ATELECTASIS.

Data from ClinicalTrials.gov NCT01147926 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation.
   Yiannakou Y, Piessevaux H, Bouchoucha M, Schiefke I, et al · · 2015 · cited 82× · PMID 25869393 · DOI 10.1038/ajg.2015.115
2. The PAC-SYM questionnaire for chronic constipation: defining the minimal important difference.
   Yiannakou Y, Tack J, Piessevaux H, Dubois D, et al · · 2017 · cited 64× · PMID 28983926 · DOI 10.1111/apt.14349
3. Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.
   Camilleri M, Piessevaux H, Yiannakou Y, Tack J, et al · · 2016 · cited 61× · PMID 27056037 · DOI 10.1007/s10620-016-4147-9
4. Efficacy of Prucalopride for Chronic Idiopathic Constipation: An Analysis of Participants With Moderate to Very Severe Abdominal Bloating.
   Staller K, Hinson J, Kerstens R, Spalding W, et al · · 2022 · cited 11× · PMID 34585675 · DOI 10.14309/ajg.0000000000001521
5. A Review of the Cardiovascular Safety of Prucalopride in Patients With Chronic Idiopathic Constipation.
   Tack J, Derakhchan K, Gabriel A, Spalding W, et al · · 2023 · cited 10× · PMID 36927957 · DOI 10.14309/ajg.0000000000002249
6. Tissue distribution and abuse potential of prucalopride: findings from non-clinical and clinical studies.
   Derakhchan K, Lou Z, Wang H, Baughman R. · · 2023 · cited 1× · PMID 36876155 · DOI 10.7573/dic.2022-6-1
7. Safety/Efficacy of Prucalopride in Korean Patients with Chronic Constipation: Post-marketing Surveillance.
   Yeon SE, Kim SY, Chung WC, Jeon SW, et al · · 2021 · cited 1× · PMID 34697276 · DOI 10.4166/kjg.2021.099
8. UEG Week 2014 Poster Presentations
   · 2014 · cited 1×