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

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

Official Title
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A Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-group, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

Conditions
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Chronic Constipation

Intervention / Treatment
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* Drug: linaclotide acetate
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 72 ug linaclotide acetate<br> | Drug: linaclotide acetate<br>* oral, once daily.<br>|
| Active Comparator: 145 ug linaclotide acetate<br> | Drug: linaclotide acetate<br>* oral, once daily.<br>|
| Active Comparator: 290 ug linaclotide acetate<br> | Drug: linaclotide acetate<br>* oral, once daily.<br>|
| Active Comparator: 579 ug linaclotide acetate<br> | Drug: linaclotide acetate<br>* oral, once daily.<br>|
| Placebo Comparator: Matching Placebo<br> | Drug: Matching placebo<br>* oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SBM 75% Responder for the Treatment Period (Based on the Normalized Rate) | 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. | Change from Baseline to Week 4 | 
| CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate) | 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 to Week 4 | 
| Change From Baseline in the Weekly Normalized CSBM Rate for the Treatment Period | 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 to Week 4 | 
| Change From Baseline in Stool Consistency (BSFS) Score for the Treatment Period | 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 to Week 4 | 
| Change From Baseline in Straining Score for the Treatment Period | 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. | Change from Baseline to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Constipation, Chronic Constipation, Microbia, linaclotide, linaclotide acetate, MD-1100