Evaluation of the Efficacy and Safety of Lubiprostone in Adults With Mixed or Unsubtyped Irritable Bowel Syndrome

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02544152
• Collaborator: Takeda (Industry), Sucampo AG (Industry)
• Enrollment: 71
• Locations: 16
• Arms: 2
• Actual Duration (Months): 22
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

A study of the efficacy and safety of Lubiprostone in subjects diagnosed with IBS-M/IBS-U.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: Lubiprostone; Drug: Placebo	Phase 2

Detailed Description

To assess the efficacy and safety of oral lubiprostone, as compared to matching placebo, when administered orally (at 8 mcg twice daily [BID]) in subjects diagnosed with IBS-M/IBS-U.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Care provider and outcomes assessor were also blinded
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Lubiprostone in Adult Subjects With Mixed or Unsubtyped Irritable Bowel Syndrome (IBS-M/IBS-U)
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lubiprostone Participants receive 8 mcg lubiprostone capsules twice daily (BID)	Drug: Lubiprostone; 8 mcg administered orally twice daily (BID); Other Names: Amitiza
Placebo Comparator: Placebo Participants receive 0 mcg capsules BID	Drug: Placebo; Matching placebo, 0 mcg administered orally twice daily (BID); Other Names: Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants Classified as an Overall Responder for Abdominal Pain [within 12 weeks]

   An overall responder for abdominal pain is defined as a participant who is a weekly responder for at least 75% of observed treatment weeks.

Secondary Outcome Measures

1. Number of Participants Classified as a Weekly Responder for Abdominal Pain [within 12 weeks]

   Participants rate their pain on a pain intensity scale where 0=no pain and 10=worst pain. A higher score means the pain is worse. A weekly responder for abdominal pain is defined as a participant reporting ≥ 30% reduction from baseline in average of 24-hour worst abdominal pain scores for the preceding week.

2. Number of Participants Classified as a Monthly Responder for Abdominal Pain [within 3 months]

   A monthly responder for abdominal pain is defined as a participant who is a weekly responder for abdominal pain at least 2 of 4 weeks in the preceding month.

3. Number of Participants Classified as a Weekly Responder for Stool Consistency [within 12 weeks]

   A weekly responder for stool consistency is defined as a participant having at least 50% reduction from baseline in percentage of days with extreme stool consistency for a given week.

4. Number of Participants Classified as a Monthly Responder for Stool Consistency [within 3 months]

   A monthly responder for stool consistency is defined as a participant who is a weekly responder for stool consistency at least 2 of 4 weeks in the preceding month.

5. Number of Participants Classified as an Overall Responder for Stool Consistency [within 3 months]

   An overall responder for stool consistency is defined as a participant who qualifies as a weekly responder for stool consistency for at least 75% of observed treatment weeks.

6. Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms [within 12 weeks]

   A participant who achieves adequate relief of IBS symptoms during the preceding week is classified as a weekly responder for IBS symptoms.

7. Number of Participants Classified as a Monthly Responder for IBS Symptoms [within 3 months]

   A participant who is a weekly responder for IBS symptoms for at least 2 of the 4 weeks in the preceding month is classified as a monthly responder for IBS symptoms.

8. Number of Participants Classified as an Overall Responder for IBS Symptoms [within 3 months]

   A participant who is a weekly responder for IBS symptoms for at least 75% of observed treatment weeks is classified as an overall responder for IBS symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject meets the diagnosis of IBS-M or IBS-U as confirmed using the adapted ROME III Diagnostic Questionnaire for Adult Functional GI Disorders.

• Subject Screening diary entries must show an average worst abdominal pain in the past 24 hours score of at least 4 on a 11-point scale.

• Subject must be on a stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors if taking antidepressants.

Exclusion Criteria:

• Subject has current diagnosis of IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C), according to Rome III Criteria.

• Any gastrointestinal (GI) condition, other than IBS-related, affecting GI motility or defecation.

• Medical/surgical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	E Squared Research, Inc.	Huntsville	Alabama	United States	35801
2	Arkansas Gastroenterology	North Little Rock	Arkansas	United States	72117
3	GW Research Inc.	Chula Vista	California	United States	91910
4	Inland Empire Liver Foundation	Rialto	California	United States	92377
5	Prestige Clinical Research Center	Miami	Florida	United States	33133
6	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida	United States	34684
7	Meritus Center for Clinical Research	Hagerstown	Maryland	United States	21742
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	PMG Research of Charlotte	Charlotte	North Carolina	United States	28210
10	PMG Research of Charlotte	Concord	North Carolina	United States	28025
11	Cumberland Research Associates, LLC	Fayetteville	North Carolina	United States	28304
12	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
13	Clinical Research Solutions	Jackson	Tennessee	United States	38305
14	Houston Endoscopy Research Center	Houston	Texas	United States	77079
15	Wellness Clinical Research Associates	McKinney	Texas	United States	75071
16	Advanced Clinical Research Associates	Plano	Texas	United States	75093

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Takeda
• Sucampo AG

Investigators

• Study Director: Global Clinical Leader, MD, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT02544152
• Other Study ID Numbers: SCMP-0211-201
• First Posted: Sep 9, 2015
• Last Update Posted: Dec 27, 2019
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Lubiprostone

Study Results

Participant Flow

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Period Title: Overall Study
STARTED	34	37
Modified Intent to Treat (mITT)	34	37
Safety Analysis Set (SAS)	34	37
COMPLETED	33	30
NOT COMPLETED	1	7

Baseline Characteristics

Arm/Group Title	Placebo	Lubiprostone	Total
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID	Total of all reporting groups
Overall Participants	34	37	71
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	31 91.2%	34 91.9%	65 91.5%
>=65 years	3 8.8%	3 8.1%	6 8.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	45	49	48
Sex: Female, Male (Count of Participants)
Female	26 76.5%	32 86.5%	58 81.7%
Male	8 23.5%	5 13.5%	13 18.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.9%	0 0%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 20.6%	4 10.8%	11 15.5%
White	26 76.5%	33 89.2%	59 83.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%	37 100%	71 100%
Baseline Abdominal Pain (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.90 (1.340)	5.37 (1.406)	5.62 (1.390)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Classified as an Overall Responder for Abdominal Pain
Description	An overall responder for abdominal pain is defined as a participant who is a weekly responder for at least 75% of observed treatment weeks.
Time Frame	within 12 weeks

Outcome Measure Data

Analysis Population Description

modified Intent to Treat (mITT), defined as all randomized subjects who take at least one dose of study medication.

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Count of Participants [Participants]	10 29.4%	11 29.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lubiprostone
	Comments	P-value is from a Cochran-Mantel-Haenszel (CMH) test stratified by sex and baseline stool consistency
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.9870
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Number of Participants Classified as a Weekly Responder for Abdominal Pain
Description	Participants rate their pain on a pain intensity scale where 0=no pain and 10=worst pain. A higher score means the pain is worse. A weekly responder for abdominal pain is defined as a participant reporting ≥ 30% reduction from baseline in average of 24-hour worst abdominal pain scores for the preceding week.
Time Frame	within 12 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Week 1	7 20.6%	7 18.9%
Week 2	13 38.2%	8 21.6%
Week 3	11 32.4%	12 32.4%
Week 4	13 38.2%	19 51.4%
Week 5	15 44.1%	18 48.6%
Week 6	16 47.1%	15 40.5%
Week 7	14 41.2%	14 37.8%
Week 8	11 32.4%	18 48.6%
Week 9	13 38.2%	15 40.5%
Week 10	15 44.1%	12 32.4%
Week 11	14 41.2%	14 37.8%
Week 12	10 29.4%	12 32.4%

3. Secondary Outcome

Title	Number of Participants Classified as a Monthly Responder for Abdominal Pain
Description	A monthly responder for abdominal pain is defined as a participant who is a weekly responder for abdominal pain at least 2 of 4 weeks in the preceding month.
Time Frame	within 3 months

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Month 1	12 35.3%	14 37.8%
Month 2	16 47.1%	16 43.2%
Month 3	15 44.1%	13 35.1%

4. Secondary Outcome

Title	Number of Participants Classified as a Weekly Responder for Stool Consistency
Description	A weekly responder for stool consistency is defined as a participant having at least 50% reduction from baseline in percentage of days with extreme stool consistency for a given week.
Time Frame	within 12 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Week 1	5 14.7%	12 32.4%
Week 2	6 17.6%	11 29.7%
Week 3	5 14.7%	10 27%
Week 4	7 20.6%	10 27%
Week 5	11 32.4%	9 24.3%
Week 6	8 23.5%	7 18.9%
Week 7	8 23.5%	9 24.3%
Week 8	6 17.6%	9 24.3%
Week 9	6 17.6%	5 13.5%
Week 10	8 23.5%	10 27%
Week 11	7 20.6%	6 16.2%
Week 12	8 23.5%	8 21.6%

5. Secondary Outcome

Title	Number of Participants Classified as a Monthly Responder for Stool Consistency
Description	A monthly responder for stool consistency is defined as a participant who is a weekly responder for stool consistency at least 2 of 4 weeks in the preceding month.
Time Frame	within 3 months

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Month 1	3 8.8%	12 32.4%
Month 2	12 35.3%	9 24.3%
Month 3	7 20.6%	7 18.9%

6. Secondary Outcome

Title	Number of Participants Classified as an Overall Responder for Stool Consistency
Description	An overall responder for stool consistency is defined as a participant who qualifies as a weekly responder for stool consistency for at least 75% of observed treatment weeks.
Time Frame	within 3 months

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Count of Participants [Participants]	0 0%	3 8.1%

7. Secondary Outcome

Title	Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms
Description	A participant who achieves adequate relief of IBS symptoms during the preceding week is classified as a weekly responder for IBS symptoms.
Time Frame	within 12 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Week 1	14 41.2%	9 24.3%
Week 2	16 47.1%	14 37.8%
Week 3	18 52.9%	15 40.5%
Week 4	21 61.8%	20 54.1%
Week 5	22 64.7%	19 51.4%
Week 6	19 55.9%	17 45.9%
Week 7	16 47.1%	17 45.9%
Week 8	17 50%	20 54.1%
Week 9	18 52.9%	14 37.8%
Week 10	15 44.1%	15 40.5%
Week 11	18 52.9%	14 37.8%
Week 12	4 11.8%	6 16.2%

8. Secondary Outcome

Title	Number of Participants Classified as a Monthly Responder for IBS Symptoms
Description	A participant who is a weekly responder for IBS symptoms for at least 2 of the 4 weeks in the preceding month is classified as a monthly responder for IBS symptoms.
Time Frame	within 3 months

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Month 1	21 61.8%	16 43.2%
Month 2	20 58.8%	18 48.6%
Month 3	17 50%	15 40.5%

9. Secondary Outcome

Title	Number of Participants Classified as an Overall Responder for IBS Symptoms
Description	A participant who is a weekly responder for IBS symptoms for at least 75% of observed treatment weeks is classified as an overall responder for IBS symptoms.
Time Frame	within 3 months

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)	Participants receive 8 mcg lubiprostone capsules BID
Measure Participants	34	37
Count of Participants [Participants]	11 32.4%	10 27%

Adverse Events

Time Frame	13 weeks
Adverse Event Reporting Description	Treatment-emergent adverse events, defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication.
Arm/Group Title	Placebo		Lubiprostone
Arm/Group Description	Participants receive 0 mcg capsules twice daily (BID)		Participants receive 8 mcg lubiprostone capsules BID
All Cause Mortality
	Placebo		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/37 (0%)
Serious Adverse Events
	Placebo		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		1/37 (2.7%)
Gastrointestinal disorders
Colitis	0/34 (0%)		1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Placebo		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/34 (23.5%)		12/37 (32.4%)
Endocrine disorders
Diabetic retinal oedema	1/34 (2.9%)		0/37 (0%)
Gastrointestinal disorders
Nausea	1/34 (2.9%)		2/37 (5.4%)
Abdominal pain	1/34 (2.9%)		1/37 (2.7%)
Colitis	0/34 (0%)		1/37 (2.7%)
Diarrhoea	1/34 (2.9%)		1/37 (2.7%)
Dyspepsia	0/34 (0%)		1/37 (2.7%)
Rectal haemorrhage	0/34 (0%)		1/37 (2.7%)
Vomiting	0/34 (0%)		1/37 (2.7%)
Hepatobiliary disorders
Cholecystitis chronic	1/34 (2.9%)		0/37 (0%)
Cholelithiasis	1/34 (2.9%)		0/37 (0%)
Infections and infestations
Urinary tract infection	0/34 (0%)		4/37 (10.8%)
Viral infection	0/34 (0%)		1/37 (2.7%)
Ear infection	1/34 (2.9%)		0/37 (0%)
Influenza	1/34 (2.9%)		0/37 (0%)
Mastitis	1/34 (2.9%)		0/37 (0%)
Sinusitis	2/34 (5.9%)		0/37 (0%)
Investigations
Mean cell volume increased	1/34 (2.9%)		0/37 (0%)
Metabolism and nutrition disorders
Hypophosphataemia	0/34 (0%)		1/37 (2.7%)
Psychiatric disorders
Anxiety	1/34 (2.9%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/34 (2.9%)		0/37 (0%)
Surgical and medical procedures
Cholecystectomy	1/34 (2.9%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.