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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01424228

Acronym

SPD555-401

Enrollment

364

Registered

2011-08-26

Start date

2011-04-06

Completion date

2012-12-19

Last updated

2021-06-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Constipation

Keywords

Long term, Constipation, Digestive signs and symptoms

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.

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).

Interventions

DRUGplacebo

Placebo matching tablet 2 mg once daily before breakfast for 24 weeks

DRUGprucalopride

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks	Over 24 week treatment period	—
Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks	Baseline and Over 24 week treatment period	—
Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week	Over 24 week treatment period	—
Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period	Over 24 week treatment period	—
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.
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	—
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)
Percentage of Subjects With an Increase of ≥1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks	Over 24 week treatment period	—
Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks	Baseline and Over 24 week treatment period	—
Time to First SCBM After Investigational Product Intake on Day 1 and Day 28	Day 1 and 28	—
Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks	Baseline and Over 24 week treatment period	—
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.
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.
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.
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.
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	—

Countries

Belgium, Czechia, Hungary, Italy, Poland, Romania, Slovakia, Spain, Sweden

Participant flow

Participants by arm

Arm	Count
Placebo Tablet once daily before breakfast	180
Prucalopride 1 mg or 2 mg tablet once daily before breakfast	181
Total	361

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	10	14
Overall Study	inclusion/exclusion criteria not met	2	2
Overall Study	Lack of Efficacy	5	7
Overall Study	Non-compliance	2	0
Overall Study	Sponsor's decision	9	12
Overall Study	Unplanned journey	0	1
Overall Study	Withdrawal by Subject	27	11
Overall Study	Worsening of symptoms	1	0

Baseline characteristics

Characteristic	Placebo	Total	Prucalopride
Age, Continuous	48.3 years STANDARD_DEVIATION 16.25	48.9 years STANDARD_DEVIATION 16	49.4 years STANDARD_DEVIATION 15.78
Age, Customized <65 years	149 Participants	295 Participants	146 Participants
Age, Customized > = 65 years to <75 years	20 Participants	46 Participants	26 Participants
Age, Customized >=75 years	11 Participants	20 Participants	9 Participants
Region of Enrollment Belgium	8 Participants	19 Participants	11 Participants
Region of Enrollment Czech Republic	6 Participants	14 Participants	8 Participants
Region of Enrollment Hungary	29 Participants	60 Participants	31 Participants
Region of Enrollment Italy	19 Participants	37 Participants	18 Participants
Region of Enrollment Poland	34 Participants	65 Participants	31 Participants
Region of Enrollment Romania	38 Participants	75 Participants	37 Participants
Region of Enrollment Slovakia	28 Participants	57 Participants	29 Participants
Region of Enrollment Spain	11 Participants	19 Participants	8 Participants
Region of Enrollment Sweden	9 Participants	18 Participants	9 Participants
Sex: Female, Male Female	153 Participants	308 Participants	155 Participants
Sex: Female, Male Male	27 Participants	53 Participants	26 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	23 / 180	41 / 181
serious Total, serious adverse events	4 / 180	4 / 181

Outcome results

Primary

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

Time frame: Over 24 week treatment period

Population: 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	Measure	Value (NUMBER)
Placebo	The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period	20.7 percentage of subjects
Prucalopride	The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period	25.1 percentage of subjects

p-value: 0.367Cochran-Mantel-Haenszel

Secondary