Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03097861
• Collaborator: Sucampo AG (Industry), Sucampo Pharmaceuticals, Inc. (Industry)
• Enrollment: 552
• Locations: 67
• Arms: 3
• Actual Duration (Months): 5.2
• Patients Per Site: 8.2
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the bioequivalence of sprinkle and capsule formulations of lubiprostone, as compared to placebo, when administered orally in participants with Chronic Idiopathic Constipation (CIC).

Condition or Disease	Intervention/Treatment	Phase
Chronic Idiopathic Constipation	Drug: Lubiprostone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 552 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Double-blinded, Multicenter Study of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo, in Adult Subjects With Chronic Idiopathic Constipation
• Actual Study Start Date: Mar 13, 2017
• Actual Primary Completion Date: Aug 17, 2017
• Actual Study Completion Date: Aug 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lubiprostone Capsule Lubiprostone 24 mcg capsule twice daily (BID) for 7 days.	Drug: Lubiprostone; 24 mcg administered orally BID; Other Names: Amitiza
Experimental: Lubiprostone Sprinkle Lubiprostone 24 mcg sprinkle BID for 7 days.	Drug: Lubiprostone; 24 mcg administered orally BID; Other Names: Amitiza
Placebo Comparator: Placebo Placebo matching to lubiprostone (sprinkle/capsule) BID for 7 days.	Drug: Placebo; 24 mcg administered orally BID

Outcome Measures

Primary Outcome Measures

1. Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week [during the 1-week treatment period]

   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.

Secondary Outcome Measures

1. Mean SBM Consistency Score Within 1 Week [during the 1-week treatment period]

   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.

2. Mean SBM Straining Score Within 1 Week [during the 1-week treatment period]

   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.

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From first dose of study medication to follow-up (up to 15 days)]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Either has medically-confirmed diagnosis of chronic constipation (per Rome III), or meets the diagnosis as confirmed using the Rome III constipation module questionnaire during the Screening period.

• Is male or female, 18 or older years of age

• Should be on stable dose of fiber supplement or a concomitant medication for the indication of lowering blood pressure

Exclusion Criteria:

• Has any gastrointestinal (GI) condition, other than constipation, affecting GI motility or defecation

• Is unable to eat or drink, take oral medications, or to hold down oral medications due to vomiting

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Birmingham	Alabama	United States	35216
2	Investigative Site	Foley	Alabama	United States	36535
3	Investigative Site	Little Rock	Arkansas	United States	72212
4	Investigative Site	Anaheim	California	United States	92805
5	Investigative Sitee	Chula Vista	California	United States	91910
6	Investigative Site	Garden Grove	California	United States	92840
7	Investigative Site	Long Beach	California	United States	90806
8	Investigative Site	Los Angeles	California	United States	90057
9	Investigative Site	Panorama City	California	United States	91402
10	Investigative Site	San Diego	California	United States	92103
11	Investigative Site	San Marcos	California	United States	92078
12	Investigative Site	Upland	California	United States	91786
13	Investigative Site	Colorado Springs	Colorado	United States	80909
14	Investigative Site	New London	Connecticut	United States	06320
15	Investigative Site	Clearwater	Florida	United States	33765
16	Investigative Site	Coral Springs	Florida	United States	33065
17	Investigative Site	DeLand	Florida	United States	32720
18	Investigative Site	Hialeah	Florida	United States	33012
19	Investigative Site	Jupiter	Florida	United States	33458
20	Investigative Site	Miami	Florida	United States	33142
21	Investigative Site 2	Miami	Florida	United States	33143
22	Investigative Site	Miami	Florida	United States	33143
23	Investigative Site	Miami	Florida	United States	33165
24	Investigative Site	Orlando	Florida	United States	32806
25	Investigative Site	Plantation	Florida	United States	33322
26	Investigative Sitee	Port Orange	Florida	United States	32129
27	Investigative Site	Port Saint Lucie	Florida	United States	34952
28	Investigative Site	Tampa	Florida	United States	33609
29	Investigative Site	Tampa	Florida	United States	33634
30	Investigative Site	West Palm Beach	Florida	United States	33409
31	Investigative Site	Athens	Georgia	United States	30607
32	Investigative Site	Snellville	Georgia	United States	30078
33	Investigative Site	Stockbridge	Georgia	United States	30281
34	Investigative Site	Blackfoot	Idaho	United States	83221
35	Investigative Site	Boise	Idaho	United States	83712
36	Investigative Site	Meridian	Idaho	United States	83642
37	Investigative Site	Lake Charles	Louisiana	United States	70601
38	Investigative Site	New Orleans	Louisiana	United States	70124
39	Investigative Site	Shreveport	Louisiana	United States	71101
40	Investigative Site	Chevy Chase	Maryland	United States	20815
41	Investigative Site	Hagerstown	Maryland	United States	21742
42	Investigative Site	New Bedford	Massachusetts	United States	02740
43	Investigative Site	Jackson	Missouri	United States	39202
44	Investigative Sitee	Bellevue	Nebraska	United States	68005
45	Investigative Site	Las Vegas	Nevada	United States	89119
46	Investigative Site	Bronx	New York	United States	10459
47	Investigative Sitee	High Point	North Carolina	United States	27262
48	Investigative Site	Raleigh	North Carolina	United States	27612
49	Investigative Site	Cleveland	Ohio	United States	44122
50	Investigative Site	Mentor	Ohio	United States	44060
51	Investigative Site	Midwest City	Oklahoma	United States	73110
52	Investigative Site	Philadelphia	Pennsylvania	United States	19152
53	Investigative Site	Charleston	South Carolina	United States	29406
54	Investigative Site	Spartanburg	South Carolina	United States	29303
55	Investigative Site	Chattanooga	Tennessee	United States	37421
56	Investigative Site 2	Jackson	Tennessee	United States	38305
57	Investigative Site	Jackson	Tennessee	United States	38305
58	Investigative Site	Houston	Texas	United States	77058
59	Investigative Site	Houston	Texas	United States	77099
60	Investigative Site	Longview	Texas	United States	75605
61	Investigative Site	McAllen	Texas	United States	78504
62	Investigative Site	Sugar Land	Texas	United States	77479
63	Investigative Site	Layton	Utah	United States	84041
64	Investigative Site	Taylorsville	Utah	United States	84123
65	Investigative Site	West Jordan	Utah	United States	84088
66	Investigative Site	Newport News	Virginia	United States	23606
67	Investigative Site	Richmond	Virginia	United States	23220

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Sucampo AG
• Sucampo Pharmaceuticals, Inc.

Investigators

• Study Director: Global Clinical Leader, Mallinckrodt

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 6, 2017

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT03097861
• Other Study ID Numbers: SCMP-0211-302
• First Posted: Mar 31, 2017
• Last Update Posted: Jan 14, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Constipation; Lubiprostone

Study Results

Participant Flow

Recruitment Details	This trial was conducted at 66 investigative sites in the United States.
Pre-assignment Detail	Actual randomization ratio of sprinkle:placebo:capsule (2:1:1) was different than the planned randomization ratio (1:1:1)

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.	Lubiprostone 24 mcg sprinkle BID for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.
Period Title: Overall Study
STARTED	145	276	131
Safety Population	143	275	130
Modified Intent to Treat	143	275	130
Completers	129	255	121
Per-protocol Population (PP)	126	234	113
COMPLETED	138	254	122
NOT COMPLETED	7	22	9

Baseline Characteristics

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule	Total
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.	Lubiprostone 24 mcg sprinkle BID for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.	Total of all reporting groups
Overall Participants	126	234	113	473
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (13.32)	47.4 (13.17)	48.8 (13.38)	47.6 (13.25)
Sex: Female, Male (Count of Participants)
Female	105 83.3%	202 86.3%	92 81.4%	399 84.4%
Male	21 16.7%	32 13.7%	21 18.6%	74 15.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	31 24.6%	64 27.4%	33 29.2%	128 27.1%
Not Hispanic or Latino	95 75.4%	170 72.6%	80 70.8%	345 72.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.4%	2 1.8%	3 0.6%
Asian	3 2.4%	12 5.1%	3 2.7%	18 3.8%
Native Hawaiian or Other Pacific Islander	1 0.8%	2 0.9%	1 0.9%	4 0.8%
Black or African American	50 39.7%	99 42.3%	48 42.5%	197 41.6%
White	71 56.3%	120 51.3%	59 52.2%	250 52.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.8%	0 0%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week
Description	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.
Time Frame	during the 1-week treatment period

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule
Arm/Group Description	Matching placebo	Lubiprostone 24 mcg sprinkle twice daily (BID) for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.
Measure Participants	126	234	113
Baseline	1.38 (0.692)	1.37 (0.693)	1.35 (0.720)
Week 1	3.68 (2.164)	4.82 (3.658)	5.74 (3.786)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lubiprostone Sprinkle
	Comments
	Type of Statistical Test	Other
	Comments	Treatment p-value is from ANCOVA using SBM count as dependent variable, treatment as fixed effect and baseline count as random effect
Statistical Test of Hypothesis	p-Value	=0.0020
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lubiprostone Capsule
	Comments	Treatment p-value is from ANCOVA using SBM count as dependent variable, treatment as fixed effect and baseline count as random effect
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Mean SBM Consistency Score Within 1 Week
Description	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.
Time Frame	during the 1-week treatment period

Outcome Measure Data

Analysis Population Description

PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each categorical time point.

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.	Lubiprostone 24 mcg sprinkle BID for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.
Measure Participants	123	230	111
Baseline	2.47 (1.122)	2.39 (1.211)	2.28 (1.045)
Week 1	3.43 (1.270)	3.94 (1.516)	4.22 (1.409)

3. Secondary Outcome

Title	Mean SBM Straining Score Within 1 Week
Description	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.
Time Frame	during the 1-week treatment period

Outcome Measure Data

Analysis Population Description

PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each time point.

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.	Lubiprostone 24 mcg sprinkle BID for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.
Measure Participants	126	234	113
Baseline	2.39 (0.739)	2.31 (0.911)	2.40 (0.892)
Week 1	1.76 (0.871)	1.45 (0.937)	1.19 (0.917)

4. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	From first dose of study medication to follow-up (up to 15 days)

Outcome Measure Data

Analysis Population Description

Safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.

Arm/Group Title	Placebo	Lubiprostone Sprinkle	Lubiprostone Capsule
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.	Lubiprostone 24 mcg sprinkle BID for 7 days.	Lubiprostone 24 mcg capsule BID for 7 days.
Measure Participants	143	275	130
Count of Participants [Participants]	21 16.7%	40 17.1%	73 64.6%

Adverse Events

Time Frame	from first dose of study medication through a 1-week follow-up (up to 15 days)
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		Lubiprostone Sprinkle		Lubiprostone Capsule
Arm/Group Description	Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days.		Lubiprostone 24 mcg sprinkle BID for 7 days.		Lubiprostone 24 mcg capsule BID for 7 days.
All Cause Mortality
	Placebo		Lubiprostone Sprinkle		Lubiprostone Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/143 (0%)		0/275 (0%)		0/130 (0%)
Serious Adverse Events
	Placebo		Lubiprostone Sprinkle		Lubiprostone Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/143 (0%)		0/275 (0%)		0/130 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Lubiprostone Sprinkle		Lubiprostone Capsule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/143 (10.5%)		50/275 (18.2%)		29/130 (22.3%)
Gastrointestinal disorders
Diarrhea	4/143 (2.8%)		22/275 (8%)		13/130 (10%)
Nausea	3/143 (2.1%)		10/275 (3.6%)		11/130 (8.5%)
Abdominal pain	3/143 (2.1%)		4/275 (1.5%)		4/130 (3.1%)
Vomiting	0/143 (0%)		0/275 (0%)		4/130 (3.1%)
Nervous system disorders
Headache	5/143 (3.5%)		17/275 (6.2%)		4/130 (3.1%)

Limitations/Caveats

Actual randomization ratio (2:1:1) was different than the planned ratio (1:1:1).

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.