Phase 3 N=487 Randomized Quadruple-blind Treatment

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

Chronic Constipation · Constipation

Bottom Line

View on ClinicalTrials.gov: NCT01642914 ↗

Enrolled (actual)

487

Serious AEs

1.7%

Results posted

Apr 2016

Primary outcome: Primary: 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder — 13; 24; 158; 129 participants — p=0.0264

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Linaclotide 290 micrograms (Drug); Linaclotide 145 micrograms (Drug); Matching placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Forest Laboratories
Primary completion: May 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder	13; 24; 158; 129	0.0264 sig
SECONDARY 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder	13; 24; 158; 129	0.0264 sig
SECONDARY Change From Baseline in 12-Week Abdominal Bloating	-1.583; -2.476; -2.456	—
SECONDARY Percent Change From Baseline in 12-week Abdominal Bloating	-22.65; -34.52; -34.22	—
SECONDARY Percent Change From Baseline in Abdominal Bloating at Week 12	-31.41; -45.43; -47.12	0.0054 sig
SECONDARY 6/12 Week Abdominal Bloating 30% Responder	50; 62; 69; 121; 91; 90	—
SECONDARY Change From Baseline in 12-week CSBM Frequency Rate	1.020; 2.309; 2.292	—
SECONDARY Change From Baseline in CSBM Frequency Rate at Week 1.	0.641; 1.984; 1.746	—
SECONDARY Change From Baseline in CSBM Frequency Rate at Week 4.	1.063; 2.756; 2.678	—
SECONDARY Change From Baseline in CSBM Frequency Rate at Week 8	1.347; 2.803; 2.319	—
SECONDARY Change From Baseline in CSBM Frequency Rate at Week 12	1.074; 2.272; 2.488	—
SECONDARY Change From Baseline in 12-Week SBM Frequency Rate	1.480; 3.481; 3.550	—
SECONDARY Change From Baseline in SBM Frequency Rate at Week 1	1.840; 4.168; 4.125	—
SECONDARY Change From Baseline in SBM Frequency Rate at Week 4	1.420; 4.045; 3.872	—
SECONDARY Change From Baseline in SBM Frequency Rate at Week 8	1.638; 3.674; 3.785	—
SECONDARY Change From Baseline in SBM Frequency Rate at Week 12	1.288; 3.085; 2.983	—
SECONDARY Change From Baseline in the Number of Days With a Spontaneous Bowel Movement (SBM)	1.086; 2.279; 2.143	—
SECONDARY SBM Within 24 Hours After the First Dose of Investigational Product	72; 94; 94; 99; 59; 65	0.0006 sig
SECONDARY Time to Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product	28.07; 12.53; 19.35	.0054 sig
SECONDARY Change From Baseline in 12-week Stool Consistency	0.797; 1.925; 2.304	—
SECONDARY Change From Baseline in Stool Consistency at Week 12	0.845; 2.061; 2.358	—
SECONDARY Change From Baseline in 12-week Severity of Straining	-0.812; -1.495; -1.512	—
SECONDARY Change From Baseline in Severity of Straining at Week 12	-1.021; -1.654; -1.686	—
SECONDARY 9/12 Week Mild Straining and Diarrhea-free Responder	15; 38; 27; 156; 115; 132	—

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:
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)

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01642914). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.