OIC: Prucalopride Effects on Subjects With Chronic Non-cancer Pain Suffering From Opioid Induced Constipation

• Sponsor: Shire (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01117051
• Collaborator: (none)
• Enrollment: 174
• Location: 1
• Arms: 2
• Actual Duration (Months): 26.8
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

The study will evaluate the efficacy, safety and tolerability of prucalopride over 12 weeks of treatment in subjects aged 18 years and older with chronic non-cancer pain, suffering from opioid induced constipation.

Condition or Disease	Intervention/Treatment	Phase
Non-cancer Pain; Opioid Induced Constipation	Drug: placebo; Drug: prucalopride	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 174 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Prucalopride in Subjects With Chronic Non-cancer Pain Suffering From Opioid Induced Constipation
• Actual Study Start Date: May 19, 2010
• Actual Primary Completion Date: Aug 13, 2012
• Actual Study Completion Date: Aug 13, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo placebo	Drug: placebo; placebo
Active Comparator: Resolor prucalopride	Drug: prucalopride; 1 or 2 mg prucalopride once daily before breakfast

Outcome Measures

Primary Outcome Measures

1. Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week [12 weeks]

   A bowel movement (BM) was defined as spontaneous if no laxatives were taken in the 24 hours preceding that BM.

Secondary Outcome Measures

1. Plasma Concentration of Prucalopride at Week 2 [Week 2]

2. Plasma Concentration of Prucalopride at Week 8 [Week 8]

Eligibility Criteria

Criteria

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

Inclusion criteria to be assessed at screening:

1. Male or non-pregnant, non-breast-feeding female outpatient ≥18 years.

2. Has chronic pain of any aetiology (except cancer pain) requiring daily maintenance treatment with opioids;has been on stable daily opioid dose during at least the previous 2 weeks; and is expected to remain on stable daily dose of opioids for at least 15 weeks after Visit 1.

3. Subject is suffering from OIC (i.e. secondary to chronic opioid use).

4. Subject agrees to stop his/her laxative treatment and is willing to use rescue medication.

Main exclusion criteria to be assessed at screening:

1. Constipation is thought to be drug-induced (except for opioids)

2. Disallowed medication is being used

3. Subject was on chronic therapy for chronic constipation prior to start of opioid therapy

4. Subject is suffering from secondary causes of chronic constipation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Leuven		Belgium

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: NCT01117051
• Other Study ID Numbers: M0001-C301; SPD555-301; 2009-015652-20
• First Posted: May 5, 2010
• Last Update Posted: Jun 11, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Opioid induced constipation/prucalopride chronic non-cancer pain; Subjects with chronic non-cancer pain suffering from OIC
• Additional relevant MeSH terms: Constipation; Opioid-Induced Constipation; Prucalopride

Study Results

Participant Flow

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	placebo once daily before breakfast for up to 12 weeks	1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks
Period Title: Overall Study
STARTED	86	88
COMPLETED	73	77
NOT COMPLETED	13	11

Baseline Characteristics

Arm/Group Title	Placebo	Prucalopride	Total
Arm/Group Description	placebo once daily before breakfast for up to 12 weeks	1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks	Total of all reporting groups
Overall Participants	83	86	169
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (11.67)	55.7 (12.15)	56.7 (11.92)
Age, Customized (Count of Participants)
Between >=18 and <65 years	62 74.7%	66 76.7%	128 75.7%
Between >=65 and <75 years	11 13.3%	11 12.8%	22 13%
>=75 years	10 12%	9 10.5%	19 11.2%
Sex: Female, Male (Count of Participants)
Female	61 73.5%	62 72.1%	123 72.8%
Male	22 26.5%	24 27.9%	46 27.2%
Region of Enrollment (Count of Participants)
Belgium	8 9.6%	9 10.5%	17 10.1%
Bulgaria	4 4.8%	5 5.8%	9 5.3%
Czech Republic	40 48.2%	38 44.2%	78 46.2%
Germany	6 7.2%	7 8.1%	13 7.7%
France	2 2.4%	2 2.3%	4 2.4%
United Kingdom	13 15.7%	14 16.3%	27 16%
Hungary	2 2.4%	1 1.2%	3 1.8%
Netherlands	0 0%	1 1.2%	1 0.6%
Poland	6 7.2%	5 5.8%	11 6.5%
Romania	5 6%	6 7%	11 6.5%

Outcome Measures

1. Primary Outcome

Title	Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week
Description	A bowel movement (BM) was defined as spontaneous if no laxatives were taken in the 24 hours preceding that BM.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population includes all subjects who were randomized into the study and who had received at least 1 dose of investigational medication.

Arm/Group Title	Placebo	Prucalopride
Arm/Group Description	once daily before breakfast for up to 12 weeks	1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks
Measure Participants	83	86
Number [percentage of subjects]	39.8	48.8

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	0.305
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Plasma Concentration of Prucalopride at Week 2
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

ITT (subjects in the ITT whose post-dose samples were collected outside the 5-hour sampling window were not used in the plasma concentration calculation)

Arm/Group Title	Prucalopride
Arm/Group Description	1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks
Measure Participants	62
pre-dose	2.827 (1.5989)
5 hours post-dose	6.107 (2.8839)

3. Secondary Outcome

Title	Plasma Concentration of Prucalopride at Week 8
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

ITT (subjects in the ITT whose post-dose samples were collected outside the 5-hour sampling window were not used in the plasma concentration calculation)

Arm/Group Title	Prucalopride
Arm/Group Description	1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks
Measure Participants	53
pre-dose	3.179 (1.9066)
5 hours post-dose	6.615 (2.5758)

Adverse Events

Arm/Group Title	Placebo		Prucalopride
Arm/Group Description	once daily before breakfast for up to 12 weeks		1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks
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	2/83 (2.4%)		2/86 (2.3%)
Gastrointestinal disorders
Intestinal obstruction	0/83 (0%)		1/86 (1.2%)
Infections and infestations
Hepatitis A	1/83 (1.2%)		0/86 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/83 (0%)		1/86 (1.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/83 (1.2%)		0/86 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/83 (36.1%)		30/86 (34.9%)
Gastrointestinal disorders
Nausea	5/83 (6%)		9/86 (10.5%)
Flatulence	1/83 (1.2%)		4/86 (4.7%)
Abdominal pain upper	2/83 (2.4%)		3/86 (3.5%)
Diarrhea	4/83 (4.8%)		3/86 (3.5%)
Abdominal pain	4/83 (4.8%)		2/86 (2.3%)
Vomiting	3/83 (3.6%)		2/86 (2.3%)
Rectal hemorrhage	2/83 (2.4%)		1/86 (1.2%)
Infections and infestations
Influenza	1/83 (1.2%)		2/86 (2.3%)
Nasopharyngitis	2/83 (2.4%)		1/86 (1.2%)
Injury, poisoning and procedural complications
Fall	1/83 (1.2%)		2/86 (2.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/83 (1.2%)		4/86 (4.7%)
Pain in extremity	2/83 (2.4%)		0/86 (0%)
Nervous system disorders
Headache	2/83 (2.4%)		4/86 (4.7%)
Skin and subcutaneous tissue disorders
Rash	0/83 (0%)		2/86 (2.3%)
Vascular disorders
Hypertension	2/83 (2.4%)		0/86 (0%)

Limitations/Caveats

Due to the early termination of the study, results should be interpreted with caution.

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.