Trial Outcomes & Findings for Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo (NCT NCT03097861)
NCT ID: NCT03097861
Last Updated: 2020-01-14
Results Overview
Observed SBM count was based on the observed data reported in the electronic daily diary for the actual number of SBMs during the 1-week treatment period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
552 participants
Primary outcome timeframe
during the 1-week treatment period
Results posted on
2020-01-14
Participant Flow
This trial was conducted at 66 investigative sites in the United States.
Actual randomization ratio of sprinkle:placebo:capsule (2:1:1) was different than the planned randomization ratio (1:1:1)
Participant milestones
| Measure |
Placebo
Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.
|
Lubiprostone Sprinkle
Lubiprostone 24 mcg sprinkle BID for 7 days.
|
Lubiprostone Capsule
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
145
|
276
|
131
|
|
Overall Study
Safety Population
|
143
|
275
|
130
|
|
Overall Study
Modified Intent to Treat
|
143
|
275
|
130
|
|
Overall Study
Completers
|
129
|
255
|
121
|
|
Overall Study
Per-protocol Population (PP)
|
126
|
234
|
113
|
|
Overall Study
COMPLETED
|
138
|
254
|
122
|
|
Overall Study
NOT COMPLETED
|
7
|
22
|
9
|
Reasons for withdrawal
| Measure |
Placebo
Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.
|
Lubiprostone Sprinkle
Lubiprostone 24 mcg sprinkle BID for 7 days.
|
Lubiprostone Capsule
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
8
|
4
|
|
Overall Study
Investigator Decision
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
7
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
5
|
3
|
|
Overall Study
Reason not provided
|
3
|
1
|
1
|
Baseline Characteristics
Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo
Baseline characteristics by cohort
| Measure |
Placebo
n=126 Participants
Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.
|
Lubiprostone Sprinkle
n=234 Participants
Lubiprostone 24 mcg sprinkle BID for 7 days.
|
Lubiprostone Capsule
n=113 Participants
Lubiprostone 24 mcg capsule BID for 7 days.
|
Total
n=473 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
46.7 years
STANDARD_DEVIATION 13.32 • n=99 Participants
|
47.4 years
STANDARD_DEVIATION 13.17 • n=107 Participants
|
48.8 years
STANDARD_DEVIATION 13.38 • n=206 Participants
|
47.6 years
STANDARD_DEVIATION 13.25 • n=7 Participants
|
|
Sex: Female, Male
Female
|
105 Participants
n=99 Participants
|
202 Participants
n=107 Participants
|
92 Participants
n=206 Participants
|
399 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
74 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
31 Participants
n=99 Participants
|
64 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
128 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
95 Participants
n=99 Participants
|
170 Participants
n=107 Participants
|
80 Participants
n=206 Participants
|
345 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
50 Participants
n=99 Participants
|
99 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
197 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
71 Participants
n=99 Participants
|
120 Participants
n=107 Participants
|
59 Participants
n=206 Participants
|
250 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: during the 1-week treatment periodPopulation: Per protocol population
Observed SBM count was based on the observed data reported in the electronic daily diary for the actual number of SBMs during the 1-week treatment period.
Outcome measures
| Measure |
Placebo
n=126 Participants
Matching placebo
|
Lubiprostone Sprinkle
n=234 Participants
Lubiprostone 24 mcg sprinkle twice daily (BID) for 7 days.
|
Lubiprostone Capsule
n=113 Participants
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week
Baseline
|
1.38 SBMs/week
Standard Deviation 0.692
|
1.37 SBMs/week
Standard Deviation 0.693
|
1.35 SBMs/week
Standard Deviation 0.720
|
|
Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week
Week 1
|
3.68 SBMs/week
Standard Deviation 2.164
|
4.82 SBMs/week
Standard Deviation 3.658
|
5.74 SBMs/week
Standard Deviation 3.786
|
SECONDARY outcome
Timeframe: during the 1-week treatment periodPopulation: PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each categorical time point.
Stool consistency associated with SBMs was rated according to the 7-point Bristol Stool Form Scale (1-7) where 1 = Separate hard lumps, like nuts (hard to pass), 2 = Sausage-shaped but lumpy, 3 = Like a sausage but with cracks on the surface, 4 = Like a sausage or snake, smooth and soft, 5 = Soft blobs with clear-cut edges (passed easily), 6 = Fluffy pieces with ragged edges, a mushy stool, 7 = Watery, no solid pieces; entirely liquid. Scores in the mid-range of this scale indicate better stool consistency.
Outcome measures
| Measure |
Placebo
n=123 Participants
Matching placebo
|
Lubiprostone Sprinkle
n=230 Participants
Lubiprostone 24 mcg sprinkle twice daily (BID) for 7 days.
|
Lubiprostone Capsule
n=111 Participants
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Mean SBM Consistency Score Within 1 Week
Week 1
|
3.43 score on a scale
Standard Deviation 1.270
|
3.94 score on a scale
Standard Deviation 1.516
|
4.22 score on a scale
Standard Deviation 1.409
|
|
Mean SBM Consistency Score Within 1 Week
Baseline
|
2.47 score on a scale
Standard Deviation 1.122
|
2.39 score on a scale
Standard Deviation 1.211
|
2.28 score on a scale
Standard Deviation 1.045
|
SECONDARY outcome
Timeframe: during the 1-week treatment periodPopulation: PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each time point.
Bowel straining associated with SBMs was rated on a scale of 0-4 where 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe. Higher score indicates more straining, so a worse condition.
Outcome measures
| Measure |
Placebo
n=126 Participants
Matching placebo
|
Lubiprostone Sprinkle
n=234 Participants
Lubiprostone 24 mcg sprinkle twice daily (BID) for 7 days.
|
Lubiprostone Capsule
n=113 Participants
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Mean SBM Straining Score Within 1 Week
Baseline
|
2.39 score on a scale
Standard Deviation 0.739
|
2.31 score on a scale
Standard Deviation 0.911
|
2.40 score on a scale
Standard Deviation 0.892
|
|
Mean SBM Straining Score Within 1 Week
Week 1
|
1.76 score on a scale
Standard Deviation 0.871
|
1.45 score on a scale
Standard Deviation 0.937
|
1.19 score on a scale
Standard Deviation 0.917
|
SECONDARY outcome
Timeframe: From first dose of study medication to follow-up (up to 15 days)Population: Safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
An adverse event (AE) is any untoward medical occurrence (including clinically significant changes in laboratory values or other clinical tests) experienced by a participant administered a pharmaceutical product regardless of causal relationship with the treatment. A TEAE is an episode which occur after the administration of the first dose of study medication and within 7 days after final dose.
Outcome measures
| Measure |
Placebo
n=143 Participants
Matching placebo
|
Lubiprostone Sprinkle
n=275 Participants
Lubiprostone 24 mcg sprinkle twice daily (BID) for 7 days.
|
Lubiprostone Capsule
n=130 Participants
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
21 Participants
|
40 Participants
|
73 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Lubiprostone Sprinkle
Serious events: 0 serious events
Other events: 50 other events
Deaths: 0 deaths
Lubiprostone Capsule
Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=143 participants at risk
Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.
|
Lubiprostone Sprinkle
n=275 participants at risk
Lubiprostone 24 mcg sprinkle BID for 7 days.
|
Lubiprostone Capsule
n=130 participants at risk
Lubiprostone 24 mcg capsule BID for 7 days.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
2.8%
4/143 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
8.0%
22/275 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
10.0%
13/130 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
|
Gastrointestinal disorders
Nausea
|
2.1%
3/143 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
3.6%
10/275 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
8.5%
11/130 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
3/143 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
1.5%
4/275 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
3.1%
4/130 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/143 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
0.00%
0/275 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
3.1%
4/130 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
|
Nervous system disorders
Headache
|
3.5%
5/143 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
6.2%
17/275 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
3.1%
4/130 • from first dose of study medication through a 1-week follow-up (up to 15 days)
Treatment-related Adverse Events (TRAEs) were any event with possible, probably, or definite relationship with the study medication, and with an onset date 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. TRAEs were collected in the safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
|
Additional Information
Medical Information Call Center
Mallinckrodt Pharmaceuticals
Phone: 800-556-3314
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place