Trial Outcomes & Findings for Evaluation of Prucalopride in Male Subjects With Chronic Constipation. (NCT NCT01147926)

NCT ID: NCT01147926

Last Updated: 2021-06-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 374 participants
• Primary outcome timeframe: Over 12 week treatment period
• Results posted on: 2021-06-10

Participant Flow

Participant milestones

Measure	PLACEBO Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE 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.
Overall Study STARTED	187	187
Overall Study COMPLETED	160	158
Overall Study NOT COMPLETED	27	29

Reasons for withdrawal

Measure	PLACEBO Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE 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.
Overall Study Subject Withdrew Consent	9	10
Overall Study Adverse Event	7	6
Overall Study Subject Non-Compliant	5	4
Overall Study Principal investigator left hospital	1	3
Overall Study Selection criteria not met	3	1
Overall Study Lost to Follow-up	0	2
Overall Study Sponsor's Decision	0	1
Overall Study Lack of Efficacy	1	0
Overall Study Too busy, no time for study	1	0
Overall Study Went on holiday	0	1
Overall Study Colonoscopy result	0	1

Baseline Characteristics

Evaluation of Prucalopride in Male Subjects With Chronic Constipation.

Baseline characteristics by cohort

Measure	PLACEBO n=186 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=184 Participants 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 n=370 Participants Total of all reporting groups
Age, Continuous	58.5 Years STANDARD_DEVIATION 16.28 • n=93 Participants	58.4 Years STANDARD_DEVIATION 17.57 • n=4 Participants	58.5 Years STANDARD_DEVIATION 16.91 • n=27 Participants
Age, Customized Less than 65 years	115 Participants n=93 Participants	104 Participants n=4 Participants	219 Participants n=27 Participants
Age, Customized Between 65 and 75 years	39 Participants n=93 Participants	43 Participants n=4 Participants	82 Participants n=27 Participants
Age, Customized 75 years and above	32 Participants n=93 Participants	37 Participants n=4 Participants	69 Participants n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	186 Participants n=93 Participants	184 Participants n=4 Participants	370 Participants n=27 Participants
Region of Enrollment BELGIUM	10 Participants n=93 Participants	10 Participants n=4 Participants	20 Participants n=27 Participants
Region of Enrollment BULGARIA	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants
Region of Enrollment CZECH REPUBLIC	15 Participants n=93 Participants	14 Participants n=4 Participants	29 Participants n=27 Participants
Region of Enrollment DENMARK	21 Participants n=93 Participants	19 Participants n=4 Participants	40 Participants n=27 Participants
Region of Enrollment FRANCE	20 Participants n=93 Participants	21 Participants n=4 Participants	41 Participants n=27 Participants
Region of Enrollment GERMANY	11 Participants n=93 Participants	10 Participants n=4 Participants	21 Participants n=27 Participants
Region of Enrollment NETHERLANDS	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants
Region of Enrollment POLAND	28 Participants n=93 Participants	26 Participants n=4 Participants	54 Participants n=27 Participants
Region of Enrollment ROMANIA	57 Participants n=93 Participants	56 Participants n=4 Participants	113 Participants n=27 Participants
Region of Enrollment UNITED KINGDOM	10 Participants n=93 Participants	14 Participants n=4 Participants	24 Participants n=27 Participants

PRIMARY outcome

Timeframe: Over 12 week treatment period

Population: 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.

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.

Outcome measures

Measure	PLACEBO n=181 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=177 Participants 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.
The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week	17.7 percentage of subjects	37.9 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT

Outcome measures

Measure	PLACEBO n=181 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=177 Participants 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.
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	12.2 percentage of subjects	27.7 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT

Outcome measures

Measure	PLACEBO n=181 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=177 Participants 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.
Percentage of Subjects With an Increase of at Least 1 SCBM Per Week	45.3 percentage of subjects	53.7 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

Outcome measures

Measure	PLACEBO n=172 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
SCBM Per Week	1.8 SCBM/week Standard Deviation 1.91	2.6 SCBM/week Standard Deviation 2.40

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

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.

Outcome measures

Measure	PLACEBO n=167 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
Percent SBM With a Consistency of Normal and Hard/Very Hard Normal consistency	50.8 percentage of SBM Standard Deviation 30.21	47.5 percentage of SBM Standard Deviation 31.70
Percent SBM With a Consistency of Normal and Hard/Very Hard Hard/Very hard consistency	31.9 percentage of SBM Standard Deviation 29.86	26.9 percentage of SBM Standard Deviation 28.27

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

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

Outcome measures

Measure	PLACEBO n=167 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
Percent SCBM With No Straining and Severe/Very Severe Straining No straining	9.5 percentage of SBM Standard Deviation 16.23	9.7 percentage of SBM Standard Deviation 17.40
Percent SCBM With No Straining and Severe/Very Severe Straining Severe/Very severe straining	23.7 percentage of SBM Standard Deviation 27.62	20.6 percentage of SBM Standard Deviation 27.33

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

Outcome measures

Measure	PLACEBO n=167 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
Percent SBM With Sensation of Complete Evacuation	43.2 percentage of SBM Standard Deviation 32.90	46.7 percentage of SBM Standard Deviation 34.19

SECONDARY outcome

Timeframe: Day 1

Population: mITT.

Outcome measures

Measure	PLACEBO n=181 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=177 Participants 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.
Time to First SCBM After Investigational Product Intake on Day 1	218.9 hours Interval 143.93 to 291.43	110.3 hours Interval 70.8 to 172.77

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

Outcome measures

Measure	PLACEBO n=172 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
Bisacodyl Tablets Taken Per Week	1.0 Tablets/week Standard Deviation 1.76	0.6 Tablets/week Standard Deviation 1.56

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

Outcome measures

Measure	PLACEBO n=172 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=170 Participants 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.
Days With Rescue Medication Taken Per Week	0.6 Days/week Standard Deviation 0.94	0.3 Days/week Standard Deviation 0.69

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

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.

Outcome measures

Measure	PLACEBO n=171 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=169 Participants 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.
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	30.4 percentage of subjects	34.9 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

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.

Outcome measures

Measure	PLACEBO n=171 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=169 Participants 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.
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	32.7 percentage of subjects	40.2 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

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

Outcome measures

Measure	PLACEBO n=171 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=169 Participants 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.
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	30.4 percentage of subjects	21.9 percentage of subjects

SECONDARY outcome

Timeframe: Over 12 week treatment period

Population: mITT. Not all subjects in the mITT population had data for this outcome.

The subject was asked to rate his global evaluation of the efficacy of treatment using the following 5-point scale: 0=not at all effective 1=a little bit effective 2=moderately effective 3=quite a bit effective 4=extremely effective.

Outcome measures

Measure	PLACEBO n=171 Participants Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=169 Participants 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.
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	30.4 percentage of subjects	46.7 percentage of subjects

Adverse Events

PLACEBO

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

PRUCALOPRIDE

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO n=186 participants at risk Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=184 participants at risk 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.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/186	0.54% 1/184 • Number of events 1
Cardiac disorders MYOCARDIAL ISCHAEMIA	0.54% 1/186 • Number of events 1	0.00% 0/184
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.54% 1/186 • Number of events 1	0.00% 0/184
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GLOTTIS CARCINOMA	0.54% 1/186 • Number of events 1	0.00% 0/184
Respiratory, thoracic and mediastinal disorders ATELECTASIS	0.54% 1/186 • Number of events 1	0.00% 0/184

Other adverse events

Measure	PLACEBO n=186 participants at risk Placebo matched to Prucalopride tablet orally once daily.	PRUCALOPRIDE n=184 participants at risk 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.
Gastrointestinal disorders ABDOMINAL PAIN	5.9% 11/186 • Number of events 12	4.3% 8/184 • Number of events 11
Gastrointestinal disorders DIARRHOEA	1.6% 3/186 • Number of events 3	6.5% 12/184 • Number of events 16
Gastrointestinal disorders NAUSEA	2.2% 4/186 • Number of events 4	6.0% 11/184 • Number of events 12
Nervous system disorders HEADACHE	3.8% 7/186 • Number of events 8	9.2% 17/184 • Number of events 18

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER