Dose-range-finding, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

Phase 2

Completed

Conditions: Chronic Constipation

Interventions: Drug: linaclotide acetate
Drug: Matching placebo

Registration Number: NCT00402337

Lead Sponsor: Ironwood Pharmaceuticals, Inc.

Brief Summary: The primary purpose of this study is to evaluate the efficacy and safety of administration of linaclotide acetate in patients with chronic constipation.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 310

Inclusion Criteria

Patient is 18 years of age or older
Patient meets colonoscopy requirements according to the American Gastroenterological Association
Patient meets criteria for chronic constipation including weekly bowel movement frequency requirements and reports one or more symptoms of constipation according to protocol requirements
Patient has successfully completed study requirements with no clinically-significant findings: physical exam, ECG, clinical laboratory tests
Patient is fluent in English

Exclusion Criteria

Patient reports loose or watery stools
Patient meets criteria for IBS including protocol-defined abdominal discomfort or pain
Patient may not take prohibited medications per protocol
Medical diagnoses, medical conditions, or family history that would not make the patient a good candidate for the study or limit the patient's ability to complete the clinical study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
72 ug linaclotide acetate	linaclotide acetate	-
Matching Placebo	Matching placebo	-
145 ug linaclotide acetate	linaclotide acetate	-
290 ug linaclotide acetate	linaclotide acetate	-
579 ug linaclotide acetate	linaclotide acetate	-

Primary Outcome Measures

Name	Time	Method
Change From Pretreatment in Weekly Normalized Spontaneous Bowel Movement (SBM) Frequency	Change from Baseline to Week 4	Change in SBM frequency during Weeks 1 through 4 of the treatment period from the weekly SBM rate obtained during the pretreatment period.

Secondary Outcome Measures

Name	Time	Method
SBM 75% Responder for the Treatment Period (Based on the Normalized Rate)	Change from Baseline to Week 4	A patient was an SBM 75% Responder if the patient was an SBM Responder for ≥3 of the 4 treatment period weeks. For each week of the treatment and postreatment periods, a patient was considered an SBM Responder if for that week the patient 1) completed ≥4 days of IVRS questions,2) had an SBM rate of ≥ 3 for the week, and 3) had an increase in SBM rate of ≥ 1 from their baseline weekly SBM rate.
CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate)	Change from Baseline to Week 4	A patient was a complete spontaneous bowel movement (CSBM) 75% Responder if the patient was a CSBM Responder for ≥3 of the 4 treatment period weeks. For each week of the treatment and postreatment periods, a patient was considered a CSBM Responder if for that week the patient 1) completed ≥4 days of IVRS questions,2) had a CSBM rate of ≥ 3 for the week, and 3) had an increase in CSBM rate of ≥ 1 from their baseline weekly CSBM rate.
Change From Baseline in the Weekly Normalized CSBM Rate for the Treatment Period	Change from Baseline to Week 4	CSBMs measured daily during the treatment period. During each daily phone call into the IVRS, patients were asked: How many bowel movements did you have today or yesterday after your last call?
Change From Baseline in Stool Consistency (BSFS) Score for the Treatment Period	Change from Baseline to Week 4	Stool consistency analyses were performed using the 7-point BSFS, whereby a score of 1 = difficult to pass; 2 = sausage shaped but lumpy; 3 = like a sausage but with cracks on 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; and 7 = entirely liquid.
Change From Baseline in Straining Score for the Treatment Period	Change from Baseline to Week 4	Straining was assessed using a 5-point ordinal scale, whereby a score of 1 = not at all, 2 = a little bit, 3 = a moderate amount, 4 = a great deal, and 5 = an extreme amount.