A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults

• Sponsor: Braintree Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02481947
• Collaborator: (none)
• Enrollment: 459
• Locations: 50
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 9.2
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate a daily dose of BLI400 Laxative for safety and efficacy versus lubiprostone in constipated adults.

Condition or Disease	Intervention/Treatment	Phase
Chronic Idiopathic Constipation	Drug: BLI400 Laxative; Drug: Lubiprostone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 459 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BLI400 Laxative 21 gm BLI400 powder	Drug: BLI400 Laxative; 21 gm BLI400 powder
Active Comparator: Lubiprostone 24 mcg capsule bid	Drug: Lubiprostone; 24 mcg capsule bid

Outcome Measures

Primary Outcome Measures

1. Complete Spontaneous Bowel Movement (CSBM) Response [12 weeks]

   The primary endpoint is based on the number of subjects who are weekly responders for at least 9 out of 12 weeks, with at least 3 of these weeks occurring in the last 4 weeks of treatment. A weekly responder is a subject who has ≥ 3 CSBMs and an increase from baseline of > 1 CSBM in that week.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subjects at least 18 years of age

• Constipated, defined by the following adapted ROME II definition:

1. Fewer than 3 spontaneous defecations per week and at least one of the following symptoms for at least 12 weeks (which need not be consecutive) in the preceding 12 months:

1. Straining during > 25% of defecations

2. Lumpy or hard stools in > 25% of defecations

3. Sensation of incomplete evacuation for > 25% of defecations

1. Loose stools are rarely present without the use of laxatives

2. There are insufficient criteria for IBS - loose (mushy) or watery stool in the absence of laxative use for more than 25% of bowel movements

Criteria A, B and C must be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

• Otherwise in good health, as determined by physical exam and medical history

• If female, and of child-bearing potential, is using an acceptable form of birth control

• Negative urine pregnancy test at screening, if applicable

• In the Investigator's judgment, subject is mentally competent to provide informed consent to participate in the study

Exclusion Criteria:

• Subjects with known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis, toxic megacolon

• Subjects who have had major surgery 30 days before Visit 1; appendectomy or cholecystectomy 60 days before Visit 1; abdominal, pelvic, or retroperitoneal surgery 6 months before Visit 1; bariatric surgery or surgery to remove a segment of the GI tract at any time before Visit 1

• Subjects with hypothyroidism that is being treated and for which the dose of thyroid hormone has not been stable for at least 6 weeks at the time of Visit 1

• Subjects taking laxatives, enemas or prokinetic agents that refuse to discontinue these treatments from Visit 1 until after completion of Visit 5

• Subjects who are pregnant or lactating, or intend to become pregnant during the study

• Subjects of childbearing potential who refuse a pregnancy test

• Subjects who are allergic to any study medication component

• Subjects taking narcotic analgesics or other medications known to cause constipation

• Subjects with clinically significant cardiac abnormalities identified at the Visit 1 ECG

• Subjects who, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures

• Subjects who have participated in an investigational clinical, surgical, drug, or device study within the past 30 days

• Subjects with an active history of drug or alcohol abuse

• Subjects have been hospitalized for a psychiatric condition or have made a suicide attempt during the 2 years before Visit 1

• Subjects who withdraw consent at any time prior to completion of Visit 1 procedures

• Subjects with known or suspected moderate to severe hepatic insufficiency (Child Pugh Classes B and C)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BLI Research Site 38	Mobile	Alabama	United States	36688
2	BLI Research Site 21	Tucson	Arizona	United States	85712
3	BLI Research Site 10	Anaheim	California	United States	92801
4	BLI Research Site 12	Artesia	California	United States	90701
5	BLI Research Site 28	Corona	California	United States	92879
6	BLI Research Site 30	La Mirada	California	United States	90638
7	BLI Research Site 13	Laguna Hills	California	United States	92653
8	BLI Research Site 41	Orange	California	United States	92868
9	BLI Research Site 50	Sacramento	California	United States	95821
10	BLI Research Site 23	San Diego	California	United States	92103
11	BLI Research Site 26	Brandon	Florida	United States	33511
12	BLI Research Site 4	Brandon	Florida	United States	33511
13	BLI Research Site 44	Clearwater	Florida	United States	33756
14	BLI Research Site 46	DeLand	Florida	United States	32720
15	BLI Research Site 32	Hialeah	Florida	United States	33012
16	BLI Research Site 40	Hialeah	Florida	United States	33012
17	BLI Research Site 17	Miami Lakes	Florida	United States	33016
18	BLI Research Site 43	Miami Springs	Florida	United States	33166
19	BLI Research Site 5	Miami	Florida	United States	33142
20	BLI Research Site 34	Miami	Florida	United States	33144
21	BLI Research Site 36	Miami	Florida	United States	33144
22	BLI Research Site 8	Miami	Florida	United States	33144
23	BLI Research Site 11	Orlando	Florida	United States	32801
24	BLI Research Site 18	Orlando	Florida	United States	32807
25	BLI Research Site 37	Palmetto Bay	Florida	United States	33157
26	BLI Research Site 24	Saint Petersburg	Florida	United States	33709
27	BLI Research Site 3	Tampa	Florida	United States	33607
28	BLI Research Site 1	West Palm Beach	Florida	United States	33409
29	BLI Research Site 7	Atlanta	Georgia	United States	30328
30	BLI Research Site 25	Snellville	Georgia	United States	30078
31	BLI Research Site 16	Chicago	Illinois	United States	60602
32	BLI Research Site 47	Owensboro	Kentucky	United States	42303
33	BLI Research Site 6	Monroe	Louisiana	United States	71201
34	BLI Research Site 31	West Monroe	Louisiana	United States	71291
35	BLI Research Site 49	Las Vegas	Nevada	United States	89103
36	BLI Research Site 27	New York	New York	United States	10016
37	BLI Research Site 39	Raleigh	North Carolina	United States	27609
38	BLI Research Site 14	Cincinnati	Ohio	United States	45231
39	BLI Research Site 22	Chattanooga	Tennessee	United States	37421
40	BLI Research Site 29	Knoxville	Tennessee	United States	37938
41	BLI Research Site 45	Memphis	Tennessee	United States	38119
42	BLI Research Site 19	Nashville	Tennessee	United States	37012
43	BLI Research Site 20	Austin	Texas	United States	78731
44	BLI Research Site 9	Austin	Texas	United States	78735
45	BLI Research Site 42	Carrollton	Texas	United States	75010
46	BLI Research Site 48	Channelview	Texas	United States	77530
47	BLI Research Site 2	Plano	Texas	United States	75024
48	BLI Research Site 35	Charlottesville	Virginia	United States	22911
49	BLI Research Site 15	Newport News	Virginia	United States	23606
50	BLI Research Site 33	Richland	Washington	United States	99352

Sponsors and Collaborators

• Braintree Laboratories

Investigators

• Study Director: John McGowan, MPH, Braintree Laboratories, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Braintree Laboratories
• ClinicalTrials.gov Identifier: NCT02481947
• Other Study ID Numbers: BLI400-301
• First Posted: Jun 25, 2015
• Last Update Posted: Jul 27, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Constipation; Laxatives; Lubiprostone

Study Results

Participant Flow

Arm/Group Title	BLI400 Laxative	Lubiprostone
Arm/Group Description	BLI400 Laxative (21 gm BLI400 powder per day)	Lubiprostone (24 mcg capsule bid)
Period Title: Overall Study
STARTED	230	229
COMPLETED	184	193
NOT COMPLETED	46	36

Baseline Characteristics

Arm/Group Title	BLI400 Laxative	Lubiprostone	Total
Arm/Group Description	BLI400 Laxative BLI400 Laxative: Oral laxative	Lubiprostone Lubiprostone: Oral laxative	Total of all reporting groups
Overall Participants	230	229	459
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (13.6)	45.6 (14.6)	45.5 (14.1)
Sex: Female, Male (Count of Participants)
Female	187 81.3%	179 78.2%	366 79.7%
Male	43 18.7%	50 21.8%	93 20.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	95 41.3%	98 42.8%	193 42%
Not Hispanic or Latino	135 58.7%	131 57.2%	266 58%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Asian	8 3.5%	7 3.1%	15 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	63 27.4%	68 29.7%	131 28.5%
White	156 67.8%	146 63.8%	302 65.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 0.9%	8 3.5%	10 2.2%
Region of Enrollment (participants) [Number]
United States	230 100%	229 100%	459 100%

Outcome Measures

1. Primary Outcome

Title	Complete Spontaneous Bowel Movement (CSBM) Response
Description	The primary endpoint is based on the number of subjects who are weekly responders for at least 9 out of 12 weeks, with at least 3 of these weeks occurring in the last 4 weeks of treatment. A weekly responder is a subject who has ≥ 3 CSBMs and an increase from baseline of > 1 CSBM in that week.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Per-protocol population

Arm/Group Title	BLI400 Laxative	Lubiprostone
Arm/Group Description	BLI400 Laxative (21 gm BLI400 powder)	Lubiprostone (24 mcg capsule bid)
Measure Participants	187	199
Count of Participants [Participants]	47 20.4%	56 24.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BLI400 Laxative, Lubiprostone
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin = 12.6% (pre-specified)
Statistical Test of Hypothesis	p-Value	0.016
	Comments	The a priori threshold for statistical significance was 0.05.
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Results for mortality, serious adverse events and other adverse events are based on the FDA agreed upon Safety Population (BLI400 n=225, lubiprostone n=229).
Arm/Group Title	BLI400 Laxative		Lubiprostone
Arm/Group Description	BLI400 Laxative (21 gm BLI400 powder)		Lubiprostone (24 mcg capsule bid)
All Cause Mortality
	BLI400 Laxative		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/225 (0.4%)		0/229 (0%)
Serious Adverse Events
	BLI400 Laxative		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/225 (0.9%)		1/229 (0.4%)
Gastrointestinal disorders
stomach ulcer	0/225 (0%)	0	1/229 (0.4%)	1
General disorders
Death	1/225 (0.4%)	1	0/229 (0%)	0
Infections and infestations
Cellulitis of legs	1/225 (0.4%)	1	0/229 (0%)	0
Other (Not Including Serious) Adverse Events
	BLI400 Laxative		Lubiprostone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/225 (11.6%)		15/229 (6.6%)
Gastrointestinal disorders
diarrhea	11/225 (4.9%)		12/229 (5.2%)
flatulence	17/225 (7.6%)		3/229 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sole disclosure restriction which sponsor imposes on the PI is a sixty (60) day limited restriction in order to the protect potentially proprietary information which may be patentable.