Trial Outcomes & Findings for Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation (NCT NCT00399542)

NCT ID: NCT00399542

Last Updated: 2019-12-17

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 581 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2019-12-17

Participant Flow

First subject enrolled 05/19/05; last subject observed 08/02/06, at 65 centers across the US

Subjects were enrolled after an up to 4 week screening period to meet inclusion/exclusion criteria and randomized on Day 0

Participant milestones

Measure	Lubiprostone Subjects who received active drug	Placebo Subjects who received placebo
Overall Study STARTED	387	194
Overall Study COMPLETED	303	151
Overall Study NOT COMPLETED	84	43

Reasons for withdrawal

Measure	Lubiprostone Subjects who received active drug	Placebo Subjects who received placebo
Overall Study Adverse Event	18	15
Overall Study Protocol Violation	13	3
Overall Study Withdrawal by Subject	28	10
Overall Study Lack of Efficacy	18	8
Overall Study Lost to Follow-up	6	6
Overall Study Other	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo	Total n=571 Participants Total of all reporting groups
Age, Continuous	45.5 years STANDARD_DEVIATION 12.93 • n=5 Participants	47.3 years STANDARD_DEVIATION 13.34 • n=7 Participants	46.1 years STANDARD_DEVIATION 13.08 • n=5 Participants
Sex: Female, Male Female	343 Participants n=5 Participants	179 Participants n=7 Participants	522 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	13 Participants n=7 Participants	49 Participants n=5 Participants
Height	64.7 inches STANDARD_DEVIATION 3.15 • n=5 Participants	65.0 inches STANDARD_DEVIATION 3.34 • n=7 Participants	64.8 inches STANDARD_DEVIATION 3.21 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Intention to treat (ITT), without Last Observational Carried Forward (LOCF).

Overall responder: monthly responder for at least 2 out of 3 months

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase; AND patient did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Overall Responder Status	12.1 percentage of participants	5.7 percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

Any bowel movement not associated with rescue medication use

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Spontaneous Bowel Movement Rates Change From Baseline	1.55 spontaneous bowel movements (SBMs)/week Standard Deviation 3.071	1.29 spontaneous bowel movements (SBMs)/week Standard Deviation 2.934

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Stool Consistency Change From Baseline	-0.47 units on a scale Standard Deviation 0.673	-0.37 units on a scale Standard Deviation 0.582

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Bowel Straining Change From Baseline	-0.54 units on a scale Standard Deviation 0.719	-0.42 units on a scale Standard Deviation 0.628

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Constipation Severity Change From Baseline	-0.41 units on a scale Standard Deviation 0.606	-0.33 units on a scale Standard Deviation 0.495

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Symptom Relief	0.69 units on a scale Standard Deviation 1.058	0.60 units on a scale Standard Deviation 1.043

SECONDARY outcome

Timeframe: 28 days

Population: ITT without LOCF

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase; AND patient did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Responder Rate	9.8 percentage of participants	6.8 percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: ITT without LOCF

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase; AND patient did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Responder Rate	16.1 percentage of participants	9.9 percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: ITT without LOCF

Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF:

Rescue med use did not increase; AND patient did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Responder Rate	13.5 percentage of participants	5.7 percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Abdominal Pain Change From Baseline	-0.32 units on a scale Standard Deviation 0.600	-0.29 units on a scale Standard Deviation 0.450

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Abdominal Pain Change From Baseline	-0.44 units on a scale Standard Deviation 0.707	-0.33 units on a scale Standard Deviation 0.601

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Abdominal Pain Change From Baseline	-0.47 units on a scale Standard Deviation 0.746	-0.35 units on a scale Standard Deviation 0.619

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Abdominal Bloating Change From Baseline	-0.31 units on a scale Standard Deviation 0.614	-0.28 units on a scale Standard Deviation 0.430

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Abdominal Bloating Change From Baseline	-0.43 units on a scale Standard Deviation 0.741	-0.33 units on a scale Standard Deviation 0.611

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Abdominal Bloating Change From Baseline	-0.45 units on a scale Standard Deviation 0.760	-0.35 units on a scale Standard Deviation 0.641

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

Any bowel movement not associated with rescue medication use

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Spontaneous Bowel Movement Rates Change From Baseline	1.61 SBMs/week Standard Deviation 3.191	1.39 SBMs/week Standard Deviation 3.495

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

Any bowel movement not associated with rescue medication use

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Spontaneous Bowel Movement Rates Change From Baseline	1.43 SBMs/week Standard Deviation 3.061	1.42 SBMs/week Standard Deviation 3.584

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Stool Consistency Change From Baseline	-0.50 units on a scale Standard Deviation 0.700	-0.41 units on a scale Standard Deviation 0.724

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Stool Consistency Change From Baseline	-0.49 units on a scale Standard Deviation 0.686	-0.39 units on a scale Standard Deviation 0.748

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Bowel Straining Change From Baseline	-0.62 units on a scale Standard Deviation 0.817	-0.50 units on a scale Standard Deviation 0.745

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Bowel Straining Change From Baseline	-0.63 units on a scale Standard Deviation 0.813	-0.50 units on a scale Standard Deviation 0.803

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Constipation Severity Change From Baseline	-0.51 units on a scale Standard Deviation 0.732	-0.42 units on a scale Standard Deviation 0.664

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Constipation Severity Change From Baseline	-0.53 units on a scale Standard Deviation 0.760	-0.42 units on a scale Standard Deviation 0.679

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Symptom Relief	0.79 units on a scale Standard Deviation 1.140	0.55 units on a scale Standard Deviation 1.256

SECONDARY outcome

Timeframe: 28 days

Population: ITT with LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Symptom Relief	0.75 units on a scale Standard Deviation 1.249	0.56 units on a scale Standard Deviation 1.222

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT without LOCF

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

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Quality of Life Change From Baseline	17.3 units on a scale Standard Deviation 17.46	13.4 units on a scale Standard Deviation 16.26

SECONDARY outcome

Timeframe: 28 days

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 1 Bowel Movement Rates Change From Baseline	1.30 bowel movements (BMs)/week Standard Deviation 2.787	0.87 bowel movements (BMs)/week Standard Deviation 3.104

SECONDARY outcome

Timeframe: 28 days

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 2 Bowel Movement Rates Change From Baseline	1.29 BMs/week Standard Deviation 2.875	0.95 BMs/week Standard Deviation 3.444

SECONDARY outcome

Timeframe: 28 days

Population: ITT, with LOCF

Outcome measures

Measure	Lubiprostone n=379 Participants Subjects who received active drug	Placebo n=192 Participants Subjects who received placebo
Month 3 Bowel Movement Rates Change From Baseline	1.17 BMs/week Standard Deviation 2.757	0.97 BMs/week Standard Deviation 3.309

Adverse Events

Lubiprostone

Serious events: 2 serious events

Other events: 67 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lubiprostone Subjects who received active drug	Placebo Subjects who received placebo
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/384	0.51% 1/195 • Number of events 1
Hepatobiliary disorders Cholecystitis	0.26% 1/384 • Number of events 1	0.00% 0/195
General disorders Non-cardiac chest pain	0.26% 1/384 • Number of events 1	0.00% 0/195
Gastrointestinal disorders Small intestine gangrene	0.00% 0/384	0.51% 1/195 • Number of events 1
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/384	0.51% 1/195 • Number of events 1
Gastrointestinal disorders Abdominal adhesions	0.00% 0/384	0.51% 1/195 • Number of events 1

Other adverse events

Measure	Lubiprostone Subjects who received active drug	Placebo Subjects who received placebo
Gastrointestinal disorders Nausea	8.9% 34/384 • Number of events 34	5.6% 11/195 • Number of events 11
Gastrointestinal disorders Diarrhoea	6.0% 23/384 • Number of events 23	5.1% 10/195 • Number of events 10
Nervous system disorders Headache	4.2% 16/384 • Number of events 16	5.6% 11/195 • Number of events 11

Additional Information

Raymond Panas, PhD

Sucampo Pharmaceuticals, Inc.

Phone: 301-961-3400

Email: info@sucampo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place