Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00380250
• Collaborator: Takeda (Industry)
• Enrollment: 590
• Arms: 2
• Duration (Months): 14

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the efficacy and safety of administration of lubiprostone in patients with irritable bowel syndrome with constipation.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome With Constipation	Drug: Lubiprostone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 590 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Phase 3, 12-Week, Multicenter, Double-Blind, Randomized, Efficacy and Safety Study of Lubiprostone for the Treatment of Irritable Bowel Syndrome With Constipation
• Study Start Date: May 1, 2005
• Actual Study Completion Date: Jul 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lubiprostone 8 mcg capsule twice daily (BID)	Drug: Lubiprostone
Placebo Comparator: Placebo Matching placebo capsule twice daily (BID)	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Overall Responder Rate [12 weeks]

   Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months

Secondary Outcome Measures

1. Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline [Change from baseline for month 1]

   SBMs are any bowel movement not associated with rescue medication use.

2. Month 1 Stool Consistency Change From Baseline [Change from baseline for month 1]

   0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

3. Month 1 Bowel Straining Change From Baseline [Change from baseline for month 1]

   0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

4. Month 1 Constipation Severity Change From Baseline [Change from baseline at 28 days]

   0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

5. Month 1 Symptom Relief [Change from baseline for month 1]

   Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

6. Quality of Life Change From Baseline [Change from baseline at 12 weeks]

   Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase

7. Month 2 Responder Rate [month 2 (28 days)]

   Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

8. Month 3 Responder Rate [month 3 (28 days)]

   Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse.

9. Month 1 Responder Rate [month 1 (28 days)]

   Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse.

10. Month 2 Abdominal Bloating Change From Baseline [Change from baseline for month 2]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

11. Month 3 Abdominal Bloating Change From Baseline [Change from baseline for month 3]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

12. Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline [Change from baseline for month 2]

    Any bowel movement not associated with rescue medication use

13. Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline [Change from baseline for month 3]

    Any bowel movement not associated with rescue medication use

14. Month 2 Stool Consistency Change From Baseline [Change from baseline for month 2]

    0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

15. Month 3 Stool Consistency Change From Baseline [Change from baseline for month 3]

    0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)

16. Month 2 Bowel Straining Change From Baseline [Change from baseline for month 2]

    0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

17. Month 3 Bowel Straining Change From Baseline [Change from baseline for month 3]

    0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

18. Month 2 Constipation Severity Change From Baseline [Change from baseline for month 2]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

19. Month 3 Constipation Severity Change From Baseline [Change from baseline for month 3]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

20. Month 2 Symptom Relief [Change from baseline for month 2]

    Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

21. Month 3 Symptom Relief [Change from baseline for month 3]

    Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3

22. Month 1 Abdominal Bloating Change From Baseline [Change from baseline for month 1]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

23. Month 1 Bowel Movement Frequency Rates Change From Baseline [Change from baseline for month 1]

24. Month 2 Bowel Movement Frequency Rates Change From Baseline [Change from baseline for month 2]

25. Month 3 Bowel Movement Frequency Rates Change From Baseline [Change from baseline for month 3]

26. Month 1 Abdominal Pain Change From Baseline [Change from baseline for month 1]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

27. Month 2 Abdominal Pain Change From Baseline [Change from baseline for month 2]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

28. Month 3 Abdominal Pain Change From Baseline [Change from baseline for month 3]

    0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age and older

• Stable fiber therapy

• Normal colonoscopy/sigmoidoscopy

• Able to refrain from use of medications known to treat or associated with constipation symptoms

• Experiences abdominal discomfort/pain associated with bowel movements

• Reports decreased bowel movement frequency and/or other symptoms associated with constipation

Exclusion Criteria:

• Diarrhea-predominant or alternating (diarrhea and constipation cycling) irritable bowel syndrome (IBS), or constipation other than that associated with IBS

• Open gastrointestinal or abdominal surgery prior to IBS onset

• Organic bowel disorder, mechanical bowel obstruction, pseudo-obstruction, unexplained weight loss or rectal bleeding

• Uncontrolled cardiovascular, liver or lung disease, neurologic or psychiatric disorder, other systemic disease, or abnormal laboratory tests per investigator discretion

• If female, is currently pregnant or nursing, or plans to become pregnant or nurse during the clinical study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Takeda

Investigators

• Study Director: Medical Director, MD, Sucampo Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT00380250
• Other Study ID Numbers: 0211SIB-0431
• First Posted: Sep 25, 2006
• Last Update Posted: Nov 15, 2019
• Last Verified: Jan 1, 2014

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

Study Results

Participant Flow

Recruitment Details	First subject entered 5/12/05; Last subject observation 7/18/08; Multicenter study performed at 65 study sites/centers across the US
Pre-assignment Detail	Subjects were enrolled after an up to 4 week screening period to meet inclusion/exclusion criteria and randomized on Day 0

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Period Title: Overall Study
STARTED	396	194
COMPLETED	297	139
NOT COMPLETED	99	55

Baseline Characteristics

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I	Total
Arm/Group Description	Subjects who received active drug	Subjects who received placebo	Total of all reporting groups
Overall Participants	390	193	583
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	46.7	48.1	47.2
Sex: Female, Male (Count of Participants)
Female	355 91%	180 93.3%	535 91.8%
Male	35 9%	13 6.7%	48 8.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	0 0%	1 0.2%
Asian	0 0%	1 0.5%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	53 13.6%	29 15%	82 14.1%
White	336 86.2%	160 82.9%	496 85.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	3 1.6%	3 0.5%
Height (Inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Inches]	64.9 (2.9)	64.8 (3.09)	64.9 (2.96)

Outcome Measures

1. Secondary Outcome

Title	Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline
Description	SBMs are any bowel movement not associated with rescue medication use.
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [SBM/week]	1.54 (2.462)	1.21 (2.286)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

2. Secondary Outcome

Title	Month 1 Stool Consistency Change From Baseline
Description	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.51 (0.690)	-0.33 (0.626)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

3. Secondary Outcome

Title	Month 1 Bowel Straining Change From Baseline
Description	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.53 (0.739)	-0.36 (0.694)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.050
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

4. Secondary Outcome

Title	Month 1 Constipation Severity Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline at 28 days

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.41 (0.602)	-0.29 (0.568)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.159
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

5. Secondary Outcome

Title	Month 1 Symptom Relief
Description	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	0.66 (1.212)	0.57 (1.088)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.378
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center

6. Secondary Outcome

Title	Quality of Life Change From Baseline
Description	Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase
Time Frame	Change from baseline at 12 weeks

Outcome Measure Data

Analysis Population Description

ITT without LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	16.7 (17.36)	16.8 (19.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.588
	Comments
	Method	ANCOVA
	Comments	Adjusted for clinical site

7. Primary Outcome

Title	Overall Responder Rate
Description	Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) without Last Observation Carried Forward (LOCF)

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Number [percentage of participants]	13.8 3.5%	7.8 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments	90% statistical power to detect 70.6% improvement in response with lubiprostone
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	No adjustment
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center, used to test the null hypothesis of equal rates between the 2 groups vs. the alternate hypothesis of non-equality

8. Secondary Outcome

Title	Month 2 Responder Rate
Description	Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.
Time Frame	month 2 (28 days)

Outcome Measure Data

Analysis Population Description

ITT without LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Number [percent of participants]	15.9 4.1%	9.3 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments	Sequential closed testing procedures were employed
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center, used to test the null hypothesis of equal rates between the 2 groups vs. the alternate hypothesis of non-equality

9. Secondary Outcome

Title	Month 3 Responder Rate
Description	Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse.
Time Frame	month 3 (28 days)

Outcome Measure Data

Analysis Population Description

ITT without LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Number [percent of participants]	15.9 4.1%	10.4 5.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments	Sequential closed testing procedures were employed
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center, used to test the null hypothesis of equal rates between the 2 groups vs. the alternate hypothesis of non-equality

10. Secondary Outcome

Title	Month 1 Responder Rate
Description	Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse.
Time Frame	month 1 (28 days)

Outcome Measure Data

Analysis Population Description

ITT without LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Number [percent of participants]	10.0 2.6%	6.2 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments	Sequential closed testing procedures were employed
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center, used to test the null hypothesis of equal rates between the 2 groups vs. the alternate hypothesis of non-equality

11. Secondary Outcome

Title	Month 2 Abdominal Bloating Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.42 (0.693)	-0.35 (0.621)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

12. Secondary Outcome

Title	Month 3 Abdominal Bloating Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.43 (0.734)	-0.37 (0.693)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

13. Secondary Outcome

Title	Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline
Description	Any bowel movement not associated with rescue medication use
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [SBM/week]	1.59 (2.795)	1.41 (2.587)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.334
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

14. Secondary Outcome

Title	Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline
Description	Any bowel movement not associated with rescue medication use
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [SBM/week]	1.51 (2.990)	1.39 (2.851)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.242
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

15. Secondary Outcome

Title	Month 2 Stool Consistency Change From Baseline
Description	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.53 (0.756)	-0.38 (0.658)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

16. Secondary Outcome

Title	Month 3 Stool Consistency Change From Baseline
Description	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.52 (0.725)	-0.41 (0.696)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.130
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

17. Secondary Outcome

Title	Month 2 Bowel Straining Change From Baseline
Description	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.58 (0.846)	-0.43 (0.762)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

18. Secondary Outcome

Title	Month 3 Bowel Straining Change From Baseline
Description	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.56 (0.847)	-0.45 (0.760)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.348
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

19. Secondary Outcome

Title	Month 2 Constipation Severity Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.50 (0.719)	-0.40 (0.670)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.064
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

20. Secondary Outcome

Title	Month 3 Constipation Severity Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.51 (0.755)	-0.41 (0.712)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments
	Method	van Elteren nonparametric test
	Comments

21. Secondary Outcome

Title	Month 2 Symptom Relief
Description	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	0.76 (1.278)	0.59 (1.203)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.144
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled center

22. Secondary Outcome

Title	Month 3 Symptom Relief
Description	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	0.74 (1.259)	0.57 (1.277)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.168
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Adjusted by pooled center

23. Secondary Outcome

Title	Month 1 Abdominal Bloating Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale score]	-0.30 (0.585)	-0.24 (0.516)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.615
	Comments
	Method	van Elteren nonparametic test
	Comments	Adjusted for center

24. Secondary Outcome

Title	Month 1 Bowel Movement Frequency Rates Change From Baseline
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

ITT, with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [BM/week]	1.22 (2.234)	0.88 (2.093)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	van Elteren nonparametric test
	Comments

25. Secondary Outcome

Title	Month 2 Bowel Movement Frequency Rates Change From Baseline
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

ITT, with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [BM/week]	1.23 (2.440)	1.10 (2.581)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.483
	Comments
	Method	van Elteren nonparametric test
	Comments

26. Secondary Outcome

Title	Month 3 Bowel Movement Frequency Rates Change From Baseline
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

ITT, with LOCF

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [BM/week]	1.15 (2.744)	1.04 (2.731)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.491
	Comments
	Method	van Elteren nonparametric test
	Comments

27. Secondary Outcome

Title	Month 1 Abdominal Pain Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale Score]	-0.29 (0.588)	-0.27 (0.508)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

28. Secondary Outcome

Title	Month 2 Abdominal Pain Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale Score]	-0.43 (0.695)	-0.37 (0.614)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

29. Secondary Outcome

Title	Month 3 Abdominal Pain Change From Baseline
Description	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time Frame	Change from baseline for month 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lubiprostone Study Period I	Placebo Study Period I
Arm/Group Description	Subjects who received active drug	Subjects who received placebo
Measure Participants	390	193
Mean (Standard Deviation) [Scale Score]	-0.42 (0.722)	-0.36 (0.684)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone Study Period I, Placebo Study Period I
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren nonparametric test
	Comments	Adjusted for center

Adverse Events

Time Frame	Up to 12 weeks
Adverse Event Reporting Description	Any subject who took at least 1 dose of study medication made up the safety population. The N of this population is different from both the total subjects randomized and the ITT population
Arm/Group Title	Lubiprostone Study Period I		Placebo Study Period I
Arm/Group Description	8 mcg capsules twice daily (BID)		Matching placebo capsules twice daily (BID)
All Cause Mortality
	Lubiprostone Study Period I		Placebo Study Period I
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lubiprostone Study Period I		Placebo Study Period I
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/396 (1.3%)		2/192 (1%)
Cardiac disorders
Mitral valve incompetence	1/396 (0.3%)	1	0/192 (0%)	0
Coronary artery disease	1/396 (0.3%)	1	0/192 (0%)	0
Cardiac arrest	1/396 (0.3%)	1	0/192 (0%)	0
Atrial fibrillation	1/396 (0.3%)	1	0/192 (0%)	0
Injury, poisoning and procedural complications
Fall	0/396 (0%)	0	1/192 (0.5%)	1
Back injury	0/396 (0%)	0	1/192 (0.5%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/396 (0%)	0	1/192 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid gland cancer	1/396 (0.3%)	1	0/192 (0%)	0
Breast cancer	1/396 (0.3%)	1	0/192 (0%)	0
Renal and urinary disorders
Dysuria	1/396 (0.3%)	1	0/192 (0%)	0
Other (Not Including Serious) Adverse Events
	Lubiprostone Study Period I		Placebo Study Period I
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/ (NaN)		25/ (NaN)
Gastrointestinal disorders
Nausea	47/396 (11.9%)	47	11/192 (5.7%)	11
Diarrhoea	28/396 (7.1%)	28	11/192 (5.7%)	11
Abdominal Pain	22/396 (5.6%)	22	12/192 (6.3%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.