Clinical trial NCT01642914: Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating
Official title: Phase 3b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Chronic Constipation and Prominent Abdominal Bloating at Baseline
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Constipation
Constipation
Keywords: Chronic Constipation
Abdominal Bloating
Linaclotide
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2012-07-17
Enrollment: 487
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of linaclotide compared with placebo in patients with chronic constipation (CC) and prominent abdominal bloating. This study includes an up to 3-week screening period and a 2-3 week pretreatment period. Patients who are eligible will be randomized to one of two doses of linaclotide or placebo for 12 weeks. This 12-week study will assess the effects of linaclotide on bowel movement frequency, as well as other abdominal and bowel symptoms of CC.


Eligibility criteria: Inclusion Criteria:

* Patient has completed a colonoscopy according to the American Gastroenterological Association criteria with no clinically significant findings
* Patient has successfully completed protocol procedures (with no clinically significant findings)
* Patient meets protocol criteria for Chronic Constipation(CC): \< 3 bowel movements per week and reports one or more of the following symptoms for at least 12 weeks:

  1. Straining during more than 25% of BMs
  2. Lumpy or hard stools during more than 25% of BMs
  3. Sensation of incomplete evacuation during more than 25% of BMs
* Patient demonstrates continued chronic constipation and bloating through Pretreatment Period
* Patient is compliant with Interactive voice response System (IVRS)

Exclusion Criteria:

* Patient has a history of loose or watery stools
* Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS)
* Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
* Patient has any protocol-excluded or clinically significant medical or surgical history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

Primary outcomes:
measure: 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder
timeFrame: 12-week treatment period
Secondary outcomes:
measure: 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder
timeFrame: 12-week treatment period
measure: Change From Baseline in 12-Week Abdominal Bloating
timeFrame: Baseline and 12-week treatment period
measure: Percent Change From Baseline in 12-week Abdominal Bloating
timeFrame: Baseline and 12-week treatment period
measure: Percent Change From Baseline in Abdominal Bloating at Week 12
timeFrame: Baseline and Week 12
measure: 6/12 Week Abdominal Bloating 30% Responder
timeFrame: 12-week treatment period
measure: Change From Baseline in 12-week CSBM Frequency Rate
timeFrame: Baseline and 12-week treatment period
measure: Change From Baseline in CSBM Frequency Rate at Week 1.
timeFrame: Baseline and Week 1
measure: Change From Baseline in CSBM Frequency Rate at Week 4.
timeFrame: Baseline and Week 4
measure: Change From Baseline in CSBM Frequency Rate at Week 8
timeFrame: Baseline and Week 8
measure: Change From Baseline in CSBM Frequency Rate at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in 12-Week SBM Frequency Rate
timeFrame: 12-week treatment period
measure: Change From Baseline in SBM Frequency Rate at Week 1
timeFrame: Baseline and Week 1
measure: Change From Baseline in SBM Frequency Rate at Week 4
timeFrame: Baseline and Week 4
measure: Change From Baseline in SBM Frequency Rate at Week 8
timeFrame: Baseline and Week 8
measure: Change From Baseline in SBM Frequency Rate at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Number of Days With a Spontaneous Bowel Movement (SBM)
timeFrame: Baseline and 12-week treatment period
measure: SBM Within 24 Hours After the First Dose of Investigational Product
timeFrame: 24 hours from first dose of investigational product (Day 1)
measure: Time to Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product
timeFrame: 12-week treatment period
measure: Change From Baseline in 12-week Stool Consistency
timeFrame: Baseline and 12-week treatment period
measure: Change From Baseline in Stool Consistency at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in 12-week Severity of Straining
timeFrame: Baseline and 12-week treatment period
measure: Change From Baseline in Severity of Straining at Week 12
timeFrame: Baseline and Week 12
measure: 9/12 Week Mild Straining and Diarrhea-free Responder
timeFrame: 12-week treatment period
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Forest Investigative Site 020
state: Arizona
city: Chandler
country: United States
facility: Forest Investigative Site 102
state: Arizona
city: Glendale
country: United States
facility: Forest Investigative Site 149
state: Arizona
city: Goodyear
country: United States
facility: Forest Investigative Site 126
state: Arizona
city: Phoenix
country: United States
facility: Forest Investigative Site 018
state: Arizona
city: Phoenix
country: United States
facility: Forest Investigative Site 061
state: Arizona
city: Scottsdale
country: United States
facility: Forest Investigative Site 022
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 079
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 071
state: Arizona
city: North Little Rock
country: United States
facility: Forest Investigative Site 135
state: Arkansas
city: Anaheim
country: United States
facility: Forest Investigative Site 106
state: California
city: Laguna Hills
country: United States
facility: Forest Investigative Site 104
state: California
city: Mission Hills
country: United States
facility: Forest Investigative Site 066
state: California
city: San Carlos
country: United States
facility: Forest Investigative Site 095
state: California
city: San Diego
country: United States
facility: Forest Investigative Site 009
state: California
city: Santa Monica
country: United States
facility: Forest Investigative Site 151
state: California
city: Westlake Village
country: United States
facility: Forest Investigative Site 010
state: California
city: Boulder
country: United States
facility: Forest Investigative Site 012
state: Colorado
city: Colorado Springs
country: United States
facility: Forest Investigative Site 041
state: Colorado
city: Colorado Springs
country: United States
facility: Forest Investigative Site 045
state: Colorado
city: Longmont
country: United States
facility: Forest Investigative Site 060
state: Colorado
city: Bristol
country: United States
facility: Forest Investigative Site 007
state: Connecticut
city: Waterbury
country: United States
facility: Forest Investigative Site 153
state: Connecticut
city: Boynton Beach
country: United States
facility: Forest Investigative Site 091
state: Florida
city: Bradenton
country: United States
facility: Forest Investigative Site 047
state: Florida
city: Brooksville
country: United States
facility: Forest Investigative Site 042
state: Florida
city: Coral Gables
country: United States
facility: Forest Investigative Site 133
state: Florida
city: DeLand
country: United States
facility: Forest Investigative Site 131
state: Florida
city: Ft. Myers
country: United States
facility: Forest Investigative Site 051
state: Florida
city: Inverness
country: United States
facility: Forest Investigative Site 137
state: Florida
city: Jacksonville
country: United States
facility: Forest Investigative Site 114
state: Florida
city: Jupiter
country: United States
facility: Forest Investigative Site 004
state: Florida
city: Kissimmee
country: United States
facility: Forest Investigative Site 016
state: Florida
city: Lauderdale Lakes
country: United States
facility: Forest Investigative Site 097
state: Florida
city: Miami
country: United States
facility: Forest Investigative Site 003
state: Florida
city: Miami
country: United States
facility: Forest Investigative Site 002
state: Florida
city: New Smyrna Beach
country: United States
facility: Forest Investigative Site 130
state: Florida
city: Ocala
country: United States
facility: Forest Investigative Site 040
state: Florida
city: Orlando
country: United States
facility: Forest Investigative Site 083
state: Florida
city: Oviedo
country: United States
facility: Forest Investigative Site 150
state: Florida
city: Port Orange
country: United States
facility: Forest Investigative Site 132
state: Florida
city: Seminole
country: United States
facility: Forest Investigative Site 127
state: Florida
city: St. Petersburg
country: United States
facility: Forest Investigative Site 087
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 064
state: Florida
city: Zephyrhills
country: United States
facility: Forest Investigative Site 115
state: Florida
city: Marietta
country: United States
facility: Forest Investigative Site 021
state: Georgia
city: Marietta
country: United States
facility: Forest Investigative Site 011
state: Georgia
city: Sandy Springs
country: United States
facility: Forest Investigative Site 109
state: Georgia
city: Stockbridge
country: United States
facility: Forest Investigative Site 037
state: Georgia
city: Woodstock
country: United States
facility: Forest Investigative Site 023
state: Georgia
city: Idaho Falls
country: United States
facility: Forest Investigative Site 015
state: Idaho
city: Peoria
country: United States
facility: Forest Investigative Site 122
state: Illinois
city: Rockford
country: United States
facility: Forest Investigative Site 043
state: Illinois
city: Anderson
country: United States
facility: Forest Investigative Site 107
state: Indiana
city: Clive
country: United States
facility: Forest Investigative Site 117
state: Iowa
city: Clive
country: United States
facility: Forest Investigative Site 146
state: Iowa
city: Davenport
country: United States
facility: Forest Investigative Site 143
state: Iowa
city: Iowa City
country: United States
facility: Forest Investigative Site 055
state: Iowa
city: Newton
country: United States
facility: Forest Investigative Site 028
state: Kansas
city: Overland Park
country: United States
facility: Forest Investigative Site 112
state: Kansas
city: Wichita
country: United States
facility: Forest Investigative Site 034
state: Kansas
city: Wichita
country: United States
facility: Forest Investigative Site 032
state: Kansas
city: Lexington
country: United States
facility: Forest Investigative Site 128
state: Kentucky
city: Madisonville
country: United States
facility: Forest Investigative Site 134
state: Kentucky
city: Baton Rouge
country: United States
facility: Forest Investigative Site 121
state: Louisiana
city: Metairie
country: United States
facility: Forest Investigative Site 124
state: Louisiana
city: Monroe
country: United States
facility: Forest Investigative Site 101
state: Louisiana
city: Shreveport
country: United States
facility: Forest Investigative Site 058
state: Louisiana
city: Shreveport
country: United States
facility: Forest Investigative Site 099
state: Louisiana
city: Baltimore
country: United States
facility: Forest Investigative Site 062
state: Maryland
city: Chevy Chase
country: United States
facility: Forest Investigative Site 008
state: Maryland
city: Hagerstown
country: United States
facility: Forest Investigative Site 014
state: Maryland
city: Towson
country: United States
facility: Forest Investigative Site 024
state: Maryland
city: Boston
country: United States
facility: Forest Investigative Site 006
state: Massachusetts
city: Chesterfield
country: United States
facility: Forest Investigative Site 070
state: Michigan
city: Traverse City
country: United States
facility: Forest Investigative Site 145
state: Michigan
city: Jackson
country: United States
facility: Forest Investigative Site 141
state: Mississippi
city: Fremont
country: United States
facility: Forest Investigative Site 077
state: Nebraska
city: Omaha
country: United States
facility: Forest Investigative Site 048
state: Nebraska
city: Henderson
country: United States
facility: Forest Investigative Site 052
state: Nevada
city: Las Vegas
country: United States
facility: Forest Investigative Site 080
state: Nevada
city: Clifton
country: United States
facility: Forest Investigative Site 036
state: New Jersey
city: Marlton
country: United States
facility: Forest Investigative Site 088
state: New Jersey
city: Vineland
country: United States
facility: Forest Investigative Site 033
state: New Jersey
city: Albuquerque
country: United States
facility: Forest Investigative Site 063
state: New Mexico
city: Albuquerque
country: United States
facility: Forest Investigative Site 093
state: New Mexico
city: Brooklyn
country: United States
facility: Forest Investigative Site 044
state: New York
city: Great Neck
country: United States
facility: Forest Investigative Site 017
state: New York
city: Asheboro
country: United States
facility: Forest Investigative Site 142
state: North Carolina
city: Asheville
country: United States
facility: Forest Investigative Site 094
state: North Carolina
city: Boone
country: United States
facility: Forest Investigative Site 075
state: North Carolina
city: Chapel Hill
country: United States
facility: Forest Investigative Site 123
state: North Carolina
city: Davidson
country: United States
facility: Forest Investigative Site 140
state: North Carolina
city: Fayetteville
country: United States
facility: Forest Investigative Site 039
state: North Carolina
city: Greensboro
country: United States
facility: Forest Investigative Site 031
state: North Carolina
city: Greensboro
country: United States
facility: Forest Investigative Site 029
state: North Carolina
city: Greensboro
country: United States
facility: Forest Investigative Site 078
state: North Carolina
city: Harrisburg
country: United States
facility: Forest Investigative Site 084
state: North Carolina
city: Hickory
country: United States
facility: Forest Investigative Site 073
state: North Carolina
city: Hickory
country: United States
facility: Forest Investigative Site 050
state: North Carolina
city: High Point
country: United States
facility: Forest Investigative Site 139
state: North Carolina
city: Raleigh
country: United States
facility: Forest Investigative Site 027
state: North Carolina
city: Statesville
country: United States
facility: Forest Investigative Site 119
state: North Carolina
city: Wilmington
country: United States
facility: Forest Investigative Site 089
state: North Carolina
city: Winston-Salem
country: United States
facility: Forest Investigative Site 074
state: North Carolina
city: Cincinnati
country: United States
facility: Forest Investigative Site 025
state: Ohio
city: Cincinnati
country: United States
facility: Forest Investigative Site 120
state: Ohio
city: Cleveland
country: United States
facility: Forest Investigative Site 056
state: Ohio
city: Columbus
country: United States
facility: Forest Investigative Site 026
state: Ohio
city: Dayton
country: United States
facility: Forest Investigative Site 098
state: Ohio
city: Dayton
country: United States
facility: Forest Investigative Site 090
state: Ohio
city: Mentor
country: United States
facility: Forest Investigative Site 085
state: Ohio
city: Wadsworth
country: United States
facility: Forest Investigative Site 068
state: Ohio
city: Oklahoma City
country: United States
facility: Forest Investigative Site 118
state: Oklahoma
city: Levittown
country: United States
facility: Forest Investigative Site 081
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Forest Investigative Site 001
state: Pennsylvania
city: Reading
country: United States
facility: Forest Investigative Site 110
state: Pennsylvania
city: Greer
country: United States
facility: Forest Investigative Site 116
state: South Carolina
city: Simpsonville
country: United States
facility: Forest Investigative Site 046
state: South Carolina
city: Dakota Dunes
country: United States
facility: Forest Investigative Site 092
state: South Dakota
city: Chattanooga
country: United States
facility: Forest Investigative Site 129
state: Tennessee
city: Kingsport
country: United States
facility: Forest Investigative Site 138
state: Tennessee
city: Austin
country: United States
facility: Forest Investigative Site 125
state: Texas
city: Dallas
country: United States
facility: Forest Investigative Site 035
state: Texas
city: Dallas
country: United States
facility: Forest Investigative Site 005
state: Texas
city: Fort Worth
country: United States
facility: Forest Investigative Site 111
state: Texas
city: Houston
country: United States
facility: Forest Investigative Site 100
state: Texas
city: Katy
country: United States
facility: Forest Investigative Site 067
state: Texas
city: Pasadena
country: United States
facility: Forest Investigative Site 049
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 030
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 076
state: Texas
city: Sugarland
country: United States
facility: Forest Investigative Site 065
state: Texas
city: Ogden
country: United States
facility: Forest Investigative Site 019
state: Utah
city: Salt Lake City
country: United States
facility: Forest Investigative Site 105
state: Utah
city: Sandy
country: United States
facility: Forest Investigative Site 113
state: Utah
city: Charlottesville
country: United States
facility: Forest Investigative Site 053
state: Virginia
city: Chesapeake
country: United States
facility: Forest Investigative Site 108
state: Virginia
city: Chesapeake
country: United States
facility: Forest Investigative Site 136
state: Virginia
city: Christiansburg
country: United States
facility: Forest Investigative Site 148
state: Virginia
city: Lynchburg
country: United States
facility: Forest Investigative Site 072
state: Virginia
city: Newport News
country: United States
facility: Forest Investigative Site 069
state: Virginia
city: Norfolk
country: United States
facility: Forest Investigative Site 013
state: Virginia
city: Richmond
country: United States
facility: Forest Investigative Site 038
state: Virginia
city: Spokane
country: United States
facility: Forest Investigative Site 103
state: Washington
city: La Crosse
country: United States
facility: Forest Investigative Site 082
state: Wisconsin
city: Milwaukee
country: United States
facility: Forest Investigative Site 096
state: Wisconsin
city: Sarnia
country: Canada
facility: Forest Investigative Site 059
state: Ontario
city: Sudbury
country: Canada
facility: Forest Investigative Site 054
state: Ontario
city: Toronto
country: Canada
facility: Forest Investigative Site 086
state: Ontario
city: Toronto
country: Canada
facility: Forest Investigative Site 147
state: Ontario
city: Vaughan
country: Canada
facility: Forest Investigative Site 152
state: Ontario
Study officials:
affiliation: Forest Laboratories
name: Steven Shiff, MD
role: STUDY_DIRECTOR
References:
citation: Lacy BE, Shea EP, Manuel M, Abel JL, Jiang H, Taylor DCA. Lessons learned: Chronic idiopathic constipation patient experiences with over-the-counter medications. PLoS One. 2021 Jan 11;16(1):e0243318. doi: 10.1371/journal.pone.0243318. eCollection 2021.
citation: Lacy BE, Schey R, Shiff SJ, Lavins BJ, Fox SM, Jia XD, Blakesley RE, Hao X, Cronin JA, Currie MG, Kurtz CB, Johnston JM, Lembo AJ. Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial. PLoS One. 2015 Jul 29;10(7):e0134349. doi: 10.1371/journal.pone.0134349. eCollection 2015.