Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating

NCT01642914 | Completed Phase 3 Results

• 1 other identifier: LIN-MD-04
• Study Type: interventional
• Target: 487
• Locations: 2 countries
• Sites: 151

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.

Conditions

Chronic Constipation; Constipation

Keywords

Chronic Constipation; Abdominal Bloating; Linaclotide

Outcome Measures

Primary Outcomes (1)

• 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder

  A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.

  12-week treatment period

Secondary Outcomes (23)

• 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder

  12-week treatment period

• Change From Baseline in 12-Week Abdominal Bloating

  Baseline and 12-week treatment period

• Percent Change From Baseline in 12-week Abdominal Bloating

  Baseline and 12-week treatment period

• Percent Change From Baseline in Abdominal Bloating at Week 12

  Baseline and Week 12

• 6/12 Week Abdominal Bloating 30% Responder

  12-week treatment period

Study Arms (3)

Linaclotide 290 micrograms

EXPERIMENTAL

Linaclotide 290 micrograms

Drug: Linaclotide 290 micrograms

Linaclotide 145 Micrograms

EXPERIMENTAL

Linaclotide 145 micrograms

Drug: Linaclotide 145 micrograms

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Matching placebo

Interventions

Linaclotide 290 micrograms DRUG

oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 290 micrograms

Linaclotide 145 micrograms DRUG

oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 145 Micrograms

Matching placebo DRUG

oral capsule, taken once daily each morning at least 30 minutes before breakfast

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Straining during more than 25% of BMs
• Lumpy or hard stools during more than 25% of BMs
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (151)

Forest Investigative Site 020

Chandler, Arizona, 85224, United States

Location

Forest Investigative Site 102

Chandler, Arizona, 85224, United States

Location

Forest Investigative Site 149

Glendale, Arizona, 85308, United States

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Forest Investigative Site 126

Goodyear, Arizona, 85395, United States

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Forest Investigative Site 018

Phoenix, Arizona, 85018, United States

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Forest Investigative Site 061

Phoenix, Arizona, 85020, United States

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Forest Investigative Site 022

Scottsdale, Arizona, 85251, United States

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Forest Investigative Site 079

Tucson, Arizona, 85704, United States

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Forest Investigative Site 071

Tucson, Arizona, 85712, United States

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Forest Investigative Site 135

North Little Rock, Arkansas, 72117, United States

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Forest Investigative Site 106

Anaheim, California, 92801, United States

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Forest Investigative Site 104

Laguna Hills, California, 92653, United States

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Forest Investigative Site 066

Mission Hills, California, 91345, United States

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Forest Investigative Site 095

San Carlos, California, 94070, United States

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Forest Investigative Site 009

San Diego, California, 92108, United States

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Forest Investigative Site 151

Santa Monica, California, 90404, United States

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Forest Investigative Site 010

Westlake Village, California, 91361, United States

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Forest Investigative Site 012

Boulder, Colorado, 80304, United States

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Forest Investigative Site 041

Colorado Springs, Colorado, 80904, United States

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Forest Investigative Site 045

Colorado Springs, Colorado, 80907, United States

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Forest Investigative Site 060

Longmont, Colorado, 80501, United States

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Forest Investigative Site 007

Bristol, Connecticut, 06010, United States

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Forest Investigative Site 153

Waterbury, Connecticut, 06708, United States

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Forest Investigative Site 091

Boynton Beach, Florida, 33426, United States

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Forest Investigative Site 047

Bradenton, Florida, 34208, United States

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Forest Investigative Site 042

Brooksville, Florida, 34601, United States

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Forest Investigative Site 133

Coral Gables, Florida, 33134, United States

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Forest Investigative Site 131

DeLand, Florida, 32720, United States

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Forest Investigative Site 051

Fort Myers, Florida, 33916, United States

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Forest Investigative Site 137

Inverness, Florida, 34452, United States

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Forest Investigative Site 114

Jacksonville, Florida, 32205, United States

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Forest Investigative Site 004

Jupiter, Florida, 33458, United States

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Forest Investigative Site 016

Kissimmee, Florida, 34741, United States

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Forest Investigative Site 097

Lauderdale Lakes, Florida, 33319, United States

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Forest Investigative Site 003

Miami, Florida, 33143, United States

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Forest Investigative Site 002

Miami, Florida, 33183, United States

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Forest Investigative Site 130

New Smyrna Beach, Florida, 32168, United States

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Forest Investigative Site 040

Ocala, Florida, 34471, United States

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Forest Investigative Site 083

Orlando, Florida, 32806, United States

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Forest Investigative Site 150

Oviedo, Florida, 32765, United States

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Forest Investigative Site 132

Port Orange, Florida, 32129, United States

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Forest Investigative Site 127

Seminole, Florida, 33777, United States

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Forest Investigative Site 087

St. Petersburg, Florida, 33709, United States

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Forest Investigative Site 064

Tampa, Florida, 33606, United States

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Forest Investigative Site 115

Zephyrhills, Florida, 33542, United States

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Forest Investigative Site 021

Marietta, Georgia, 30060, United States

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Forest Investigative Site 011

Marietta, Georgia, 30067, United States

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Forest Investigative Site 109

Sandy Springs, Georgia, 30328, United States

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Forest Investigative Site 037

Stockbridge, Georgia, 30281, United States

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Forest Investigative Site 023

Woodstock, Georgia, 30189, United States

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Forest Investigative Site 015

Idaho Falls, Idaho, 83404, United States

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Forest Investigative Site 122

Peoria, Illinois, 61602, United States

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Forest Investigative Site 043

Rockford, Illinois, 61107, United States

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Forest Investigative Site 107

Anderson, Indiana, 46011, United States

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Forest Investigative Site 117

Clive, Iowa, 50325, United States

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Forest Investigative Site 146

Clive, Iowa, 50325, United States

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Forest Investigative Site 143

Davenport, Iowa, 52807, United States

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Forest Investigative Site 055

Iowa City, Iowa, 52242, United States

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Forest Investigative Site 028

Newton, Kansas, 67114, United States

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Forest Investigative Site 112

Overland Park, Kansas, 66215, United States

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Forest Investigative Site 034

Wichita, Kansas, 67205, United States

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Forest Investigative Site 032

Wichita, Kansas, 67207, United States

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Forest Investigative Site 128

Lexington, Kentucky, 40509, United States

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Forest Investigative Site 134

Madisonville, Kentucky, 42431, United States

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Forest Investigative Site 121

Baton Rouge, Louisiana, 70809, United States

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Forest Investigative Site 124

Metairie, Louisiana, 70006, United States

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Forest Investigative Site 101

Monroe, Louisiana, 71201, United States

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Forest Investigative Site 058

Shreveport, Louisiana, 71101, United States

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Forest Investigative Site 099

Shreveport, Louisiana, 71103, United States

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Forest Investigative Site 062

Baltimore, Maryland, 21215, United States

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Forest Investigative Site 008

Chevy Chase, Maryland, 20815, United States

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Forest Investigative Site 014

Hagerstown, Maryland, 21742, United States

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Forest Investigative Site 024

Towson, Maryland, 21286, United States

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Forest Investigative Site 006

Boston, Massachusetts, 02135, United States

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Forest Investigative Site 070

Chesterfield, Michigan, 48047, United States

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Forest Investigative Site 145

Traverse City, Michigan, 49684, United States

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Forest Investigative Site 141

Jackson, Mississippi, 39202, United States

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Forest Investigative Site 077

Fremont, Nebraska, 68025, United States

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Forest Investigative Site 048

Omaha, Nebraska, 68134, United States

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Forest Investigative Site 052

Henderson, Nevada, 89014, United States

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Forest Investigative Site 080

Las Vegas, Nevada, 89121, United States

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Forest Investigative Site 036

Clifton, New Jersey, 07012, United States

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Forest Investigative Site 088

Marlton, New Jersey, 08053, United States

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Forest Investigative Site 033

Vineland, New Jersey, 08360, United States

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Forest Investigative Site 063

Albuquerque, New Mexico, 87106, United States

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Forest Investigative Site 093

Albuquerque, New Mexico, 87108, United States

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Forest Investigative Site 044

Brooklyn, New York, 11206, United States

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Forest Investigative Site 017

Great Neck, New York, 11021, United States

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Forest Investigative Site 142

Asheboro, North Carolina, 27203, United States

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Forest Investigative Site 094

Asheville, North Carolina, 28801, United States

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Forest Investigative Site 075

Boone, North Carolina, 28607, United States

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Forest Investigative Site 123

Chapel Hill, North Carolina, 27599-7080, United States

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Forest Investigative Site 140

Davidson, North Carolina, 28036, United States

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Forest Investigative Site 039

Fayetteville, North Carolina, 28304, United States

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Forest Investigative Site 031

Greensboro, North Carolina, 27403, United States

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Forest Investigative Site 029

Greensboro, North Carolina, 27408, United States

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Forest Investigative Site 078

Greensboro, North Carolina, 27408, United States

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Forest Investigative Site 084

Harrisburg, North Carolina, 28075, United States

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Forest Investigative Site 073

Hickory, North Carolina, 28601, United States

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Forest Investigative Site 050

Hickory, North Carolina, 28602, United States

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Forest Investigative Site 139

High Point, North Carolina, 27262, United States

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Forest Investigative Site 027

Raleigh, North Carolina, 27612, United States

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Forest Investigative Site 119

Statesville, North Carolina, 28625, United States

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Forest Investigative Site 089

Wilmington, North Carolina, 28401, United States

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Forest Investigative Site 074

Winston-Salem, North Carolina, 27103, United States

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Forest Investigative Site 025

Cincinnati, Ohio, 45242, United States

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Forest Investigative Site 120

Cincinnati, Ohio, 45249, United States

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Forest Investigative Site 056

Cleveland, Ohio, 44122, United States

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Forest Investigative Site 026

Columbus, Ohio, 43215, United States

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Forest Investigative Site 098

Dayton, Ohio, 45415, United States

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Forest Investigative Site 090

Dayton, Ohio, 45432, United States

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Forest Investigative Site 085

Mentor, Ohio, 44060, United States

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Forest Investigative Site 068

Wadsworth, Ohio, 44281, United States

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Forest Investigative Site 118

Oklahoma City, Oklahoma, 73104, United States

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Forest Investigative Site 081

Levittown, Pennsylvania, 19056, United States

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Forest Investigative Site 001

Pittsburgh, Pennsylvania, 15206, United States

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Forest Investigative Site 110

Reading, Pennsylvania, 19606, United States

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Forest Investigative Site 116

Greer, South Carolina, 29650, United States

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Forest Investigative Site 046

Simpsonville, South Carolina, 29681, United States

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Forest Investigative Site 092

Dakota Dunes, South Dakota, 57049, United States

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Forest Investigative Site 129

Chattanooga, Tennessee, 37421, United States

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Forest Investigative Site 138

Kingsport, Tennessee, 37660, United States

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Forest Investigative Site 125

Austin, Texas, 78756, United States

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Forest Investigative Site 035

Dallas, Texas, 75231, United States

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Forest Investigative Site 005

Dallas, Texas, 75234, United States

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Forest Investigative Site 111

Fort Worth, Texas, 76135, United States

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Forest Investigative Site 100

Houston, Texas, 77034, United States

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Forest Investigative Site 067

Katy, Texas, 77450, United States

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Forest Investigative Site 049

Pasadena, Texas, 77505, United States

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Forest Investigative Site 030

San Antonio, Texas, 78209, United States

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Forest Investigative Site 076

San Antonio, Texas, 78229, United States

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Forest Investigative Site 065

Sugarland, Texas, 77479, United States

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Forest Investigative Site 019

Ogden, Utah, 84405, United States

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Forest Investigative Site 105

Salt Lake City, Utah, 84107, United States

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Forest Investigative Site 113

Sandy City, Utah, 84094, United States

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Forest Investigative Site 053

Charlottesville, Virginia, 22911, United States

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Forest Investigative Site 108

Chesapeake, Virginia, 23320, United States

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Forest Investigative Site 136

Chesapeake, Virginia, 23320, United States

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Forest Investigative Site 148

Christiansburg, Virginia, 24073, United States

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Forest Investigative Site 072

Lynchburg, Virginia, 24502, United States

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Forest Investigative Site 069

Newport News, Virginia, 23606, United States

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Forest Investigative Site 013

Norfolk, Virginia, 23502, United States

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Forest Investigative Site 038

Richmond, Virginia, 23294, United States

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Forest Investigative Site 103

Spokane, Washington, 99208, United States

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Forest Investigative Site 082

La Crosse, Wisconsin, 54601, United States

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Forest Investigative Site 096

Milwaukee, Wisconsin, 53215, United States

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Forest Investigative Site 054

Greater Sudbury, Ontario, P3E 1H5, Canada

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Forest Investigative Site 059

Sarnia, Ontario, N7T 4X3, Canada

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Forest Investigative Site 086

Toronto, Ontario, M4S 1Y2, Canada

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Forest Investigative Site 147

Toronto, Ontario, M9W 4L6, Canada

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Forest Investigative Site 152

Vaughan, Ontario, L4L 4Y7, Canada

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Related Publications (2)

• 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.

  PMID: 33428631 DERIVED

• 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.

  PMID: 26222318 DERIVED

MeSH Terms

Conditions

Constipation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Steven Shiff, Executive Director, Clinical Development
• Organization: Forest Research Institute

Steven.Shiff@actavis.com

201-427-8000

Study Officials

• Steven Shiff, MD

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: July 17, 2012
• Study Start: August 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 26, 2016
• Results First Posted: April 26, 2016

Record last verified: 2016-03

Locations

US (146); CA (5)