A Study to Evaluate the Effect of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome

Study Overview
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Brief Summary
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This study is to investigate the efficacy, safety, and plasma concentration change of ASP0456 in patients with constipation-predominant irritable bowel syndrome.

Detailed Description
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This study is a multicenter, double-blind, placebo-controlled, parallel-group, comparative study to investigate dose-responses of efficacy, safety, and pharmacokinetics of ASP0456 in patients with constipation-predominant irritable bowel syndrome (IBS-C) according to the Rome III Diagnostic Criteria (2006 revised edition, established by the Rome III Committee) after oral administration of ASP0456.

Official Title
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Phase II Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study in Patients With Constipation-predominant Irritable Bowel Syndrome

Conditions
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Constipation-predominant Irritable Bowel Syndrome (IBS-C)

Intervention / Treatment
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* Drug: linaclotide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who had abdominal pain or discomfort repeatedly for at least 3 days per month during the 3 months before screening examination associated with at least 2 out of the following 3 conditions: (1) Improvement with defecation; (2) Onset associated with a change in frequency of stool; and (3) Onset associated with a change in form (appearance) of stool, and had the above symptom (IBS symptom) 6 months or more before the screening examination period. Patients with ≥25% of stools hard or lumpy (with each bowel movement occurring without antidiarrheal, laxative, suppository or enema) and <25% of them loose (mushy) or watery during the 3 months before the screening examination. Patients who had pancolonoscopy or contrast enema (or sigmoidoscopy) after the onset of IBS symptom and had no organic changes. Exclusion Criteria: Patients with a history of surgical resection of the stomach, gallbladder, small intestine or large intestine Patients with other concurrent diseases that may affect the digestive tract passage or large intestinal function Patients with other concurrent diseases that may affect the assessment of abdominal pain/discomfort Patients with blood pressure, pulse rate, clinical laboratory test, or 12-lead ECG at the time of screening examination that was rated as Grade 2 or greater on the Severity Criteria for Drug Adverse Reaction and judged to be clinically significant

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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 |
| --- | --- |
| Experimental: ASP0456 lowest dose group<br>oral | Drug: linaclotide<br>* oral<br>* Other names: ASP0456;|
| Experimental: ASP0456 low dose group<br>oral | Drug: linaclotide<br>* oral<br>* Other names: ASP0456;|
| Experimental: ASP0456 middle dose group<br>oral | Drug: linaclotide<br>* oral<br>* Other names: ASP0456;|
| Experimental: ASP0456 high dose group<br>oral | Drug: linaclotide<br>* oral<br>* Other names: ASP0456;|
| Placebo Comparator: placebo group<br>oral | Drug: placebo<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global assessment of relief of IBS symptoms Responder |  | Weekly for 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SBM (Spontaneous Bowel Movement) Responder |  | Weekly for 12 weeks | 
| CSBM (Complete SBM) Responder |  | Weekly for 12 weeks | 
| Abnormal bowel habits improvement Responder |  | Weekly for 12 weeks | 
| Abdominal pain/discomfort relief Responder |  | Weekly for 12 weeks | 
| Changes in weekly average of SBM frequency |  | Weekly for 12 weeks | 
| Changes in weekly average of CSBM frequency |  | Weekly for 12 weeks | 
| Changes in weekly average of stool form scores |  | Weekly for 12 weeks | 
| Changes in weekly average of abdominal pain/discomfort severity |  | Weekly for 12 weeks | 
| Changes in weekly average of straining severity |  | Weekly for 12 weeks | 
| Changes in IBS-QOL-J scores (entire scores or scores on the sub-scales) |  | Weekly for 12 weeks | 
| Safety assessed by the incidence of adverse events, vital signs, clinical laboratory tests and 12-lead ECGs |  | for 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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irritable bowel syndrome (IBS), linaclotide, constipation, ASP0456