Phase III Study to Evaluate the Efficacy and Safety of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy and safety of ASP0456 in patients with constipation predominant irritable bowel syndrome (IBS-C).

Detailed Description
-----------------
<Period I (double-blind period)> A multicenter, collaborative, double-blind, parallel comparative study is conducted using IBS-C patients as subjects to verify efficacy of ASP0456 and examine the safety. After the 2-week bowel habit observation period, subjects satisfying the primary enrollment criteria are randomly allocated to either ASP0456 group or placebo group, and orally administered the drug or placebo once daily before breakfast for 12 weeks. <Period II (non-blind period)> A multicenter, collaborative, non-blind, non-controlled study is conducted to examine safety and efficacy of ASP0456 in long-term administration in IBS-C patients. After Period I, subjects satisfying the transfer criteria are orally administered ASP0456 once daily before breakfast for 40 weeks.

Official Title
-----------------
Phase III Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study and Long-term Study in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

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

Intervention / Treatment
-----------------
* Drug: linaclotide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Patient with history of surgical resection of stomach, gallbladder, small intestine, or large intestine (excluding resection of appendicitis and benign polyp) Patient with history or current affection of inflammatory bowel disease (Crohn's disease or ulcerative colitis) Patient with history or current affection of ischemic colitis Patient currently affected by infectious enteritis Patient currently affected by hyperthyroidism or hypothyroidism Patient currently affected by active peptic ulcer In the case of a female patient, the one currently affected by endometriosis or uterine adenomyosis Patient with high depression or anxiety considered to influence drug evaluation Patient with history of abuse of drug or alcohol within a year before consent acquisition, or with current abuse Patient who used or underwent or will use or undergo drug/therapy/test prohibited to combine 3 days before the start of bowel habit observation period (Day -17) or thereafter Patient with history or current affection of malignant tumor Patient currently affected by serious cardiovascular disease, respiratory disease, kidney disease, hepatic disease, gastrointestinal disease (excluding IBS), hemorrhagic disease, or neural/mental disease Patient with history of drug allergy

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP0456 (Period I)<br>Up to 12 weeks | Drug: linaclotide<br>* Oral administration once daily<br>* Other names: ASP0456;|
| Placebo Comparator: Placebo (Period I)<br>Up to 12 weeks | Drug: Placebo<br>* Oral administration once daily<br>|
| Experimental: ASP0456 (Period II)<br>From 12 weeks to 52 weeks | Drug: linaclotide<br>* Oral administration once daily<br>* Other names: ASP0456;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate of Global assessment of relief of IBS symptoms during 12 weeks. | The responder of the evaluation items during the 12 weeks shall be the subject satisfying weekly responder of the evaluation items for over 6 weeks of the 12 weeks. | During 12 weeks | 
| Responder rate of CSBM during 12 weeks | CSBM: Complete Spontaneous Bowel Movement. The responder of the evaluation items during the 12 weeks shall be the subject satisfying weekly responder of the evaluation items for over 6 weeks of the 12 weeks. | During 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate of SBM during 12 weeks | SBM: Spontaneous Bowel Movement | During 12 weeks | 
| Responder rate of Abnormal bowel habits improvement during 12 weeks |  | During 12 weeks | 
| Responder rate of Abdominal pain/discomfort relief during 12 weeks |  | During 12 weeks | 
| Weekly responder rate of Global assessment of relief of IBS symptoms | The weekly responder of the evaluation items shall be the subject satisfying the followings at the time of evaluation in each week.Score of Global assessment of relief of IBS symptoms (7 scores: 1-7) is 1 or 2 | Up to 52 weeks | 
| Weekly responder rate of CSBM | Weekly responder of CSBM: The weekly mean value of CSBM frequency is more than 3 and over 1 more than the weekly mean value of CSBM frequency in the bowel habit observation period | Up to 52 weeks | 
| Weekly responder rate of SBM | Weekly responder of SBM: The weekly mean value of SBM frequency is more than 3 and over 1 more than the weekly mean value of SBM frequency in the bowel habit observation period | Up to 52 weeks | 
| Weekly responder rate of Abnormal bowel habits improvement | Score of abdominal bowel habits improvement effect (7 scores: 1-7) is 1 or 2 | Up to 52 weeks | 
| Weekly responder rate of Abdominal pain/discomfort relief | Score of abdominal pain/discomfort improvement effect (7 scores: 1-7) is 1 or 2. | Up to 52 weeks | 
| Changes in weekly average of SBM frequency, CSBM frequency, stool form scores, abdominal pain/discomfort severity, abdominal bloating severity, and straining severity. |  | From baseline to every week until 52 weeks | 
| Changes in IBS-QOL-J scores (entire scores or scores on the sub-scales) | IBS-QOL-J: Irritable bowel syndrome quality of life Japanese version | Weeks 0, 4, 8, 12, 16, 20, 24, 28, 40, 52 | 
| Percentage of subjects with SBM within 24 hours after start of the initial administration |  | Up to 24 hours | 
| Percentage of subjects with CSBM within 24 hours after start of the initial administration |  | Up to 24 hours | 
| Safety assessed by development of incidence of adverse events, vital signs, and clinical laboratory tests |  | Up to 52 weeks | 

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