Trial Outcomes & Findings for The Effectiveness of Lubiprostone in Constipated Diabetics (NCT NCT01170039)

NCT ID: NCT01170039

Last Updated: 2016-03-15

Results Overview

The average number of spontaneous bowel movements calculated per week from baseline to 8 weeks was recorded. The number of spontaneous bowel movements was recorded by the subjects in a daily stool diary and the weekly average was calculated. Spontaneous bowel movements are bowel movements within a 24 hour period independent of rescue medication use within the previous week.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 121 participants
• Primary outcome timeframe: 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks
• Results posted on: 2016-03-15

Participant Flow

Subjects were recruited from The Emory Clinic and The Atlanta Veterans Administration Hospital from August 2011 to September 2014.

121 subjects were enrolled in the study; there were 4 Screen Failures, 22 drop outs prior to randomization and 19 subjects were Early Terminations. 76 subjects were randomized and underwent a two-week wash-out period during which they did not take any laxatives.

Participant milestones

Measure	Lubiprostone Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Overall Study STARTED	37	39
Overall Study COMPLETED	29	33
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Measure	Lubiprostone Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Overall Study Withdrawal by Subject	5	3
Overall Study Lack of funding, drug not available	3	3

Baseline Characteristics

The Effectiveness of Lubiprostone in Constipated Diabetics

Baseline characteristics by cohort

Measure	Lubiprostone n=37 Participants Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=39 Participants Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.	Total n=76 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=93 Participants	39 Participants n=4 Participants	76 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	23 Participants n=93 Participants	27 Participants n=4 Participants	50 Participants n=27 Participants
Sex: Female, Male Male	14 Participants n=93 Participants	12 Participants n=4 Participants	26 Participants n=27 Participants
Region of Enrollment United States	37 participants n=93 Participants	39 participants n=4 Participants	76 participants n=27 Participants

PRIMARY outcome

Timeframe: 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks

Population: Two subjects in the Lubiprostone arm did not complete the daily stool diary at baseline. No data was analyzed for these two subjects.

The average number of spontaneous bowel movements calculated per week from baseline to 8 weeks was recorded. The number of spontaneous bowel movements was recorded by the subjects in a daily stool diary and the weekly average was calculated. Spontaneous bowel movements are bowel movements within a 24 hour period independent of rescue medication use within the previous week.

Outcome measures

Measure	Lubiprostone n=35 Participants Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=39 Participants Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 1 week	4.85 spontaneous bowel movements Standard Deviation 5.27	1.40 spontaneous bowel movements Standard Deviation 3.27
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 2 weeks	3.81 spontaneous bowel movements Standard Deviation 5.60	2.41 spontaneous bowel movements Standard Deviation 4.29
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 3 weeks	5.76 spontaneous bowel movements Standard Deviation 4.99	3.11 spontaneous bowel movements Standard Deviation 4.34
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 4 weeks	4.12 spontaneous bowel movements Standard Deviation 4.63	2.48 spontaneous bowel movements Standard Deviation 3.68
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 5 weeks	5.28 spontaneous bowel movements Standard Deviation 4.10	3.03 spontaneous bowel movements Standard Deviation 4.33
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 6 weeks	4.52 spontaneous bowel movements Standard Deviation 5.37	3.23 spontaneous bowel movements Standard Deviation 3.95
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 7 weeks	4.65 spontaneous bowel movements Standard Deviation 5.27	3.46 spontaneous bowel movements Standard Deviation 3.59
Efficacy, Measured by the Average Number of Spontaneous Bowel Movements (SBMs) Per Week 8 weeks	5.30 spontaneous bowel movements Standard Deviation 4.42	2.63 spontaneous bowel movements Standard Deviation 3.81

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Intention to treat population.

The duration of colonic transit time in hours was measured by the SmartPill pH Capsule. Colonic transit time is the time interval from the cecal entry of the capsule to anal expulsion and was measured in hours.

Outcome measures

Measure	Lubiprostone n=37 Participants Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=39 Participants Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule Baseline n=30; n=32	45.3 hours Standard Deviation 25.7	40.9 hours Standard Deviation 28.6
Efficacy, Measured by the Duration of Colonic Transit Time as Measured by the SmartPill pH Capsule 4 weeks n=24; n=22	36.2 hours Standard Deviation 28.1	47.7 hours Standard Deviation 27.7

SECONDARY outcome

Timeframe: 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks

Population: The number of participants in both arms was analyzed by Intention-to-Treat (ITT).

The number of subjects experiencing abdominal discomfort was recorded weekly.

Outcome measures

Measure	Lubiprostone n=37 Participants Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=39 Participants Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Number of Subjects With Daily Abdominal Discomfort 1 week (n=33; n=38)	24 participants	26 participants
Number of Subjects With Daily Abdominal Discomfort 2 weeks (n=32; n=37)	17 participants	20 participants
Number of Subjects With Daily Abdominal Discomfort 3 weeks (n=29; n=33)	17 participants	21 participants
Number of Subjects With Daily Abdominal Discomfort 4 weeks (n=30; n=33)	16 participants	22 participants
Number of Subjects With Daily Abdominal Discomfort 5 weeks (n=27; n=33)	13 participants	18 participants
Number of Subjects With Daily Abdominal Discomfort 6 weeks (n=26; n=30)	20 participants	14 participants
Number of Subjects With Daily Abdominal Discomfort 7 weeks (n=23; n=29)	14 participants	16 participants
Number of Subjects With Daily Abdominal Discomfort 8 weeks (n=22; n=29)	11 participants	15 participants

SECONDARY outcome

Timeframe: Screening, 8 weeks

Population: 7 subjects in the Lubiprostone arm and 7 subjects in the placebo arm did not complete the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire and therefore no data was analyzed for these subjects.

The difference in the scores on the self-reported Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire. The quality of life is measured by the by the overall scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, a validated 28-item questionnaire measuring quality of life as it pertains to constipation. The 28 items are grouped into four subscales, 1) worries and concerns, 2) physical discomfort, 3) psychosocial discomfort, and 4) satisfaction. A 5-point Likert response scale, ranging from 0 (Not at all/None of the time) to 4 (Extremely/ All of the time), is used. The subscale scores vary from 0 to 4 and the total (global) score ranges from 0 to 4. A lower score indicates better quality of life (QOL).

Outcome measures

Measure	Lubiprostone n=30 Participants Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=32 Participants Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire Global Score	-0.91 scores on a scale Standard Deviation 0.64	1.19 scores on a scale Standard Deviation 1.07
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire Physical discomfort	-1.08 scores on a scale Standard Deviation 0.71	-1.22 scores on a scale Standard Deviation 1.05
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire Psychosocial discomfort	-0.72 scores on a scale Standard Deviation 0.72	-1.13 scores on a scale Standard Deviation 1.07
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire Worries and concerns	-0.88 scores on a scale Standard Deviation 0.79	-1.18 scores on a scale Standard Deviation 1.29
Change in Scores on the Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire Satisfaction	-1.28 scores on a scale Standard Deviation 1.28	-1.26 scores on a scale Standard Deviation 1.43

Adverse Events

Lubiprostone

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lubiprostone n=37 participants at risk Subjects with diabetes and constipation received 24 mcg of lubiprostone orally twice a day for 8 weeks.	Placebo n=39 participants at risk Subjects with diabetes and constipation received a placebo pill twice a day for 8 weeks.
Gastrointestinal disorders Nausea	40.5% 15/37	23.1% 9/39
Gastrointestinal disorders Bloating	37.8% 14/37	28.2% 11/39
Gastrointestinal disorders Diarrhea	32.4% 12/37	7.7% 3/39
Gastrointestinal disorders Abdominal Pain	29.7% 11/37	20.5% 8/39
Gastrointestinal disorders Vomiting	8.1% 3/37	5.1% 2/39
Nervous system disorders Headache	21.6% 8/37	20.5% 8/39

Additional Information

Jennifer Christie

Emory University

Phone: 404-778-4594

Email: jchris6@emory.edu

Results disclosure agreements

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