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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01424228
• Collaborator: (none)
• Enrollment: 364
• Locations: 60
• Arms: 2
• Actual Duration (Months): 20.5
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Drug: placebo; Drug: prucalopride	Phase 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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 364 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Actual Study Start Date: Apr 6, 2011
• Actual Primary Completion Date: Dec 19, 2012
• Actual Study Completion Date: Dec 19, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period [Over 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.

Secondary Outcome Measures

1. Percentage of Subjects With an Increase of ≥1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks [Over 24 week treatment period]

2. Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks [Over 24 week treatment period]

3. Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks [Baseline and Over 24 week treatment period]

4. Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week [Over 24 week treatment period]

5. Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period [Over 24 week treatment period]

6. Change From Baseline in Average Consistency Per SCBM at Up to 24 Weeks [Baseline and Over 24 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.

7. 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]

8. Change From Baseline in Straining Per SCBM at Up to 24 Weeks [Baseline and Over 24 week treatment period]

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

9. 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]

10. Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks [Baseline and Over 24 week treatment period]

11. Time to First SCBM After Investigational Product Intake on Day 1 and Day 28 [Day 1 and 28]

12. Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks [Baseline and Over 24 week treatment period]

13. Change From Baseline in the Number of Days With Rescue Medication Taken Per Week at Up to 24 Weeks [Baseline and Over 24 week treatment period]

    Rescue medications include laxatives and enemas.

14. Change From Baseline in the Patient Assessment of Constipation - Symptom (PAC-SYM) Questionnaire Score at Up to the Final On Treatment Assessment Value [Baseline and Over 24 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.

15. Change From Baseline in the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score at Up to the Final On Treatment Assessment Value [Baseline and Over 24 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.

16. Change From Baseline in the Short Form-36 Health Survey (SF-36) Score at Up to the Final On Treatment Assessment Value [Baseline and Over 24 week treatment period]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Universitaire Ziekenhuizen Leuven	Leuven	Flemish Brabant	Belgium	3000
2	Cliniques Universitaires St. Luc	Brussel		Belgium	1200
3	Huisartspraktijk Jaak Mortelmans	Ham		Belgium	3945
4	Centre Hospitalier Universitaire Sart Tilman Liège	Liège		Belgium	4000
5	Fakultní Thomayerova nemocnice s poliklinikou	Praha 4 - Krc	Praha	Czechia	140 59
6	Derma Plus s.r.o.	Ceské Budejovice		Czechia	370 01
7	Oblastní nemocnice Kolín, a.s.	Kolin		Czechia	280 20
8	Diagnostika a Lécba Zažívacích Chorob, s.r.o.	Ostrava-Hrabuvka		Czechia	700 30
9	MONSE s.r.o	Praha 1		Czechia	118 33
10	Nemocnice Tábor, a.s.	Tabor		Czechia	390 03
11	Orlickoústecká Nemocnice a.s	Ústí nad Orlicí		Czechia	562 18
12	Békés Megyei Képviselotestület Pándy Kálmán Kórháza	Gyula	Bekes	Hungary	5700
13	Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinika	Szeged	Csongrad	Hungary	6720
14	Dr. Bugyi István Kórház	Szentes	Csongrad	Hungary	6600
15	Petz Aladár Megyei Oktató Kórház	Gyor	Gyor-moson-sopron	Hungary	9024
16	Karolina Kórház Rendelointézet	Mosonmagyaróvar	Gyor-moson-sopron	Hungary	9200
17	Fejér Megyei Szent György Kórház	Székesfehérvár	Pejer	Hungary	8000
18	Fundamed Háziorvosi Szövetkezet	Érd	Pest	Hungary	2030
19	UNO Medical Trials, Kft.	Budapest		Hungary	1135
20	Pannónia Magánorvosi Centrum Kft.	Budapest		Hungary	1136
21	BAZ Megyei és Egyetemi Oktató Kórház	Miskolc		Hungary	3526
22	Clinfan Kft. SMO	Szekszárd		Hungary	7100
23	CRU Hungary Kft.	Szikszó		Hungary	3800
24	Jávorszky Ödön Városi Kórház	Vác		Hungary	2600
25	Bíró Praxis Kft.	Úrhida		Hungary	8142
26	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
27	Azienda Ospedale San Martino	Genova		Italy	16132
28	Policlinico Universitario	Padova		Italy	35128
29	Fondazione IRCCS Policlinico S. Matteo	Pavia		Italy	27100
30	Policlinico Universitario Campus Biomedico	Roma		Italy	00128
31	Azienda Policlinico Umberto I di Roma	Roma		Italy	00161
32	Krakowskie Centrum Medyczne NZOZ	Krakow	Malopolskie	Poland	31-501
33	Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ	Warszawa	Mazowieckie	Poland	02-653
34	Szpital Wojewódzki w Opolu	Opole	Opolskie	Poland	45-061
35	Endoskopia Sp. z o.o.	Sopot	Pomorskie	Poland	81-756
36	Centrum Medyczne sw. Lukasza Sp. z o.o.	Czestochowa	Slaskie	Poland	42-202
37	Niepubliczny Zaklad Opieki Zdrowotnej "SONOMED"	Szczecin	Zachodniopomorskie	Poland	70-361
38	Spitalul Militar Central Bucuresti	Bucharest	Bucuresti	Romania	010825
39	Centrul Medical Sana	Bucharest	Bucuresti	Romania	011025
40	Spitalul Clinic Judetean Cluj,Clinica Medicala I	Cluj-Napoca	Cluj	Romania	400006
41	Biomed Plus SRL	Craiova	Dolj	Romania	200347
42	SC Cabinet Medical Dr. Blaj Stefan SRL	Bucharest	Sector 5	Romania	040101
43	Centrul Medical Tuculanu SRL	Timisoara	Timis	Romania	300158
44	Endocenter Medicina Integrativa SRL	Bucuresti		Romania	021978
45	Gastromedica SRL	Iasi		Romania	700506
46	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu		Romania	550245
47	CMI de Gastroenterologie Dobru Daniela	Targu-Mures		Romania	540103
48	Policlinic Algomed SRL	Timisoara		Romania	300002
49	Lama Medical Care s.r.o., Gastroentero-hepatologicke centrum Thalion	Bratislava		Slovakia	811 07
50	Gastroenterologická ambulancia	Košice		Slovakia	040 01
51	PIGEAS s.r.o.	Martin		Slovakia	03601
52	Radvanská lekáren, spol. s r.o.,	Nitra		Slovakia	950 01
53	Gastro I.s.r.o.	Prešov		Slovakia	08001
54	GEA s.r.o Gastroenterologicka ambulancia	Trnava		Slovakia	91701
55	Hospital Parc Tauli	Sabadell	Barcelona	Spain	08208
56	Hospital Clínico San Carlos	Madrid		Spain	28040
57	Hospital Universitario Nuestra Señora de Valme	Sevilla		Spain	41014
58	Sahlgrenska Universitetsjukhuset	Göteborg	Vastra Gotaland	Sweden	413 45
59	Aleris Specialistvård Sabbatsberg	Stockholm		Sweden	113 82
60	Karolinska University Hospital Solna	Stockholm		Sweden	171 76

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01424228
• Other Study ID Numbers: M0001-C401; 2011-000670-62; SPD555-401
• First Posted: Aug 26, 2011
• Last Update Posted: Jun 11, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Long term; Constipation; Digestive signs and symptoms
• Additional relevant MeSH terms: Constipation; Prucalopride

Study Results

Participant Flow

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Period Title: Overall Study
STARTED	182	182
COMPLETED	126	135
NOT COMPLETED	56	47

Baseline Characteristics

Arm/Group Title	Placebo	Prucalopride	Total
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast	Total of all reporting groups
Overall Participants	180	181	361
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (16.25)	49.4 (15.78)	48.9 (16.00)
Age, Customized (Count of Participants)
<65 years	149 82.8%	146 80.7%	295 81.7%
> = 65 years to <75 years	20 11.1%	26 14.4%	46 12.7%
>=75 years	11 6.1%	9 5%	20 5.5%
Sex: Female, Male (Count of Participants)
Female	153 85%	155 85.6%	308 85.3%
Male	27 15%	26 14.4%	53 14.7%
Region of Enrollment (Count of Participants)
Romania	38 21.1%	37 20.4%	75 20.8%
Poland	34 18.9%	31 17.1%	65 18%
Hungary	29 16.1%	31 17.1%	60 16.6%
Slovakia	28 15.6%	29 16%	57 15.8%
Italy	19 10.6%	18 9.9%	37 10.2%
Spain	11 6.1%	8 4.4%	19 5.3%
Belgium	8 4.4%	11 6.1%	19 5.3%
Sweden	9 5%	9 5%	18 5%
Czech Republic	6 3.3%	8 4.4%	14 3.9%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period
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 24 week treatment period

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT) includes all subjects randomized into the study who took at least 1 dose of investigational product. There were 21 subjects with a risk of potential unblinding due to an error in the randomization system who were excluded from the ITT Population to avoid the risk of bias to the study results.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	169	171
Number [percentage of subjects]	20.7	25.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Prucalopride
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.367
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT) includes all subjects randomized into the study who took at least 1 dose of investigational product. The 21 subjects with a risk of potential unblinding due to an error in the randomization system were excluded from the ITT Population to avoid the risk of bias to the study results.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	169	171
Number [percentage of subjects]	42.0	48.0

3. Secondary Outcome

Title	Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks
Time Frame	Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	165	158
Mean (Standard Deviation) [SCBM/week]	1.7 (1.86)	2.1 (1.96)

4. Secondary Outcome

Title	Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks
Time Frame	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	165	158
Mean (Standard Deviation) [SCBM/week]	1.3 (1.77)	1.7 (1.90)

5. Secondary Outcome

Title	Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week
Time Frame	Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT) includes all subjects randomized into the study who took at least 1 dose of investigational product. The 21 subjects with a risk of potential unblinding due to an error in the randomization system were excluded from the ITT Population to avoid the risk of bias to the study results.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	169	171
Week 1	18.3	32.2
Week 2	23.1	34.5
Week 3	22.5	32.2
Week 4	23.1	31.6
Week 5	26.6	27.5
Week 6	28.4	29.2
Week 7	29.0	29.8
Week 8	26.0	30.4
Week 9	27.8	33.3
Week 10	26.0	30.4
Week 11	25.4	37.4
Week 12	27.2	33.9
Week 13	23.7	30.4
Week 14	30.2	35.7
Week 15	24.9	29.2
Week 16	29.6	35.1
Week 17	28.4	35.1
Week 18	30.2	32.7
Week 19	32.0	32.2
Week 20	24.9	37.4
Week 21	26.6	30.4
Week 22	27.8	32.7
Week 23	30.2	31.0
Week 24	32.0	31.6

6. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT) includes all subjects randomized into the study who took at least 1 dose of investigational product. The 21 subjects with a risk of potential unblinding due to an error in the randomization system were excluded from the ITT Population to avoid the risk of bias to the study results.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	169	171
First 4-week period	18.3	26.9
Second 4-week period	23.7	25.7
Third 4-week period	23.7	29.2
Fourth 4-week period	22.5	29.2
Fifth 4-week period	23.7	33.3
Sixth 4-week period	24.9	26.9

7. Secondary Outcome

Title	Change From Baseline in Average Consistency Per SCBM at Up to 24 Weeks
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	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	67	55
Mean (Standard Deviation) [units on a scale]	-0.1 (1.79)	-0.1 (1.31)

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	67	55
Normal consistency	16.82 (42.365)	25.71 (40.1)
Hard/Very Hard consistency	-9.11 (41.495)	-13.82 (31.349)

9. Secondary Outcome

Title	Change From Baseline in Straining Per SCBM at Up to 24 Weeks
Description	Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe)
Time Frame	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	67	55
Mean (Standard Deviation) [units on a scale]	-0.44 (0.948)	-0.23 (0.870)

10. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	67	55
No straining	11.14 (39.786)	6.61 (33.916)
Severe/Very Severe straining	-9.85 (29.711)	-4.49 (28.177)

11. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	149	138
Mean (Standard Deviation) [percentage of SBM]	20.94 (32.619)	24.22 (32.878)

12. Secondary Outcome

Title	Time to First SCBM After Investigational Product Intake on Day 1 and Day 28
Time Frame	Day 1 and 28

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT) includes all subjects randomized into the study who took at least 1 dose of investigational product. The 21 subjects with a risk of potential unblinding due to an error in the randomization system were excluded from the ITT Population to avoid the risk of bias to the study results.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	169	171
Day 1	359.67	100.83
Day 28	100.58	81.78

13. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	140	144
Mean (Standard Deviation) [tablets/week]	-0.68 (1.583)	-0.97 (1.821)

14. Secondary Outcome

Title	Change From Baseline in the Number of Days With Rescue Medication Taken Per Week at Up to 24 Weeks
Description	Rescue medications include laxatives and enemas.
Time Frame	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	140	144
Mean (Standard Deviation) [days/week]	-0.42 (0.892)	-0.54 (1.018)

15. Secondary Outcome

Title	Change From Baseline in the Patient Assessment of Constipation - Symptom (PAC-SYM) Questionnaire Score at Up to the Final On Treatment Assessment Value
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	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	167	167
Mean (Standard Deviation) [units on a scale]	-0.68 (0.929)	-0.55 (0.794)

16. Secondary Outcome

Title	Change From Baseline in the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score at Up to the Final On Treatment Assessment Value
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	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	162	166
Mean (Standard Deviation) [units on a scale]	-0.73 (0.902)	-0.67 (0.932)

17. Secondary Outcome

Title	Change From Baseline in the Short Form-36 Health Survey (SF-36) Score at Up to the Final On Treatment Assessment Value
Description	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.
Time Frame	Baseline and Over 24 week treatment period

Outcome Measure Data

Analysis Population Description

ITT population. Not all subjects in the ITT population had data for this outcome.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	Tablet once daily before breakfast	1 mg or 2 mg tablet once daily before breakfast
Measure Participants	164	167
Mental component	3.786 (10.0887)	3.179 (10.5714)
Physical component	3.331 (6.9830)	2.965 (6.9320)

Adverse Events

Adverse Event Reporting Description	The Safety Population includes all subjects randomized into the study who took at least 1 dose of investigational product. Three subjects did not receive investigational product and therefore were not included in the Safety Population (n = 361).
Arm/Group Title	Placebo		Prucalopride
Arm/Group Description	Tablet once daily before breakfast		1 mg or 2 mg tablet once daily before breakfast
All Cause Mortality
	Placebo		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/180 (2.2%)		4/181 (2.2%)
Gastrointestinal disorders
Colitis ischemic	1/180 (0.6%)		0/181 (0%)
Obstruction gastric	0/180 (0%)		1/181 (0.6%)
Hepatobiliary disorders
Cholecystitis chronic	1/180 (0.6%)		0/181 (0%)
Infections and infestations
Vestibular neuronitis	1/180 (0.6%)		0/181 (0%)
Investigations
Blood pressure decreased	0/180 (0%)		1/181 (0.6%)
Electrocardiogram QT prolonged	0/180 (0%)		1/181 (0.6%)
Nervous system disorders
Cerebrovascular accident	0/180 (0%)		1/181 (0.6%)
Ischemic stroke	1/180 (0.6%)		0/181 (0%)
Psychiatric disorders
Abnormal behavior	0/180 (0%)		1/181 (0.6%)
Vascular disorders
Orthostatic hypotension	1/180 (0.6%)		0/181 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/180 (12.8%)		41/181 (22.7%)
Gastrointestinal disorders
Abdominal pain	8/180 (4.4%)		18/181 (9.9%)
Nausea	7/180 (3.9%)		13/181 (7.2%)
Nervous system disorders
Headache	10/180 (5.6%)		21/181 (11.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.