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

Phase 3
Completed
Conditions
Irritable Bowel Syndrome With Constipation (IBS-C)
Interventions
Drug: Placebo
Registration Number
NCT02316899
Lead Sponsor
Astellas Pharma Inc
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
500
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo (Period I)PlaceboUp to 12 weeks
ASP0456 (Period II)linaclotideFrom 12 weeks to 52 weeks
ASP0456 (Period I)linaclotideUp to 12 weeks
Primary Outcome Measures
NameTimeMethod
Responder rate of Global assessment of relief of IBS symptoms during 12 weeks.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.

Responder rate of CSBM during 12 weeksDuring 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.

Secondary Outcome Measures
NameTimeMethod
Responder rate of SBM during 12 weeksDuring 12 weeks

SBM: Spontaneous Bowel Movement

Responder rate of Abnormal bowel habits improvement during 12 weeksDuring 12 weeks
Responder rate of Abdominal pain/discomfort relief during 12 weeksDuring 12 weeks
Weekly responder rate of Global assessment of relief of IBS symptomsUp to 52 weeks

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

Weekly responder rate of CSBMUp to 52 weeks

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

Weekly responder rate of SBMUp to 52 weeks

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

Weekly responder rate of Abnormal bowel habits improvementUp to 52 weeks

Score of abdominal bowel habits improvement effect (7 scores: 1-7) is 1 or 2

Weekly responder rate of Abdominal pain/discomfort reliefUp to 52 weeks

Score of abdominal pain/discomfort improvement effect (7 scores: 1-7) is 1 or 2.

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)Weeks 0, 4, 8, 12, 16, 20, 24, 28, 40, 52

IBS-QOL-J: Irritable bowel syndrome quality of life Japanese version

Percentage of subjects with SBM within 24 hours after start of the initial administrationUp to 24 hours
Percentage of subjects with CSBM within 24 hours after start of the initial administrationUp to 24 hours
Safety assessed by development of incidence of adverse events, vital signs, and clinical laboratory testsUp to 52 weeks

Trial Locations

Locations (61)

Site JP00001

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Hokkaido, Japan

Site JP00048

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Aichi, Japan

Site JP00038

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Chiba, Japan

Site JP00040

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Chiba, Japan

Site JP00039

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Chiba, Japan

Site JP00042

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Chiba, Japan

Site JP00041

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Chiba, Japan

Site JP00002

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Fukuoka, Japan

Site JP00006

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Hokkaido, Japan

Site JP00061

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Fukuoka, Japan

Site JP00007

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Hokkaido, Japan

Site JP00058

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Hyogo, Japan

Site JP00057

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Hyogo, Japan

Site JP00030

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Kanagawa, Japan

Site JP00032

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Kanagawa, Japan

Site JP00034

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Kanagawa, Japan

Site JP00035

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Kanagawa, Japan

Site JP00036

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Kanagawa, Japan

Site JP00037

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Kanagawa, Japan

Site JP00056

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Kyoto, Japan

Site JP00050

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Osaka, Japan

Site JP00053

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Osaka, Japan

Site JP00054

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Osaka, Japan

Site JP00043

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Saitama, Japan

Site JP00055

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Osaka, Japan

Site JP00045

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Saitama, Japan

Site JP00044

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Saitama, Japan

Site JP00046

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Saitama, Japan

Site JP00047

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Saitama, Japan

Site JP00005

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Tokyo, Japan

Site JP00009

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Tokyo, Japan

Site JP00008

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Tokyo, Japan

Site JP00011

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Tokyo, Japan

Site JP00010

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Tokyo, Japan

Site JP00012

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Tokyo, Japan

Site JP00013

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Tokyo, Japan

Site JP00014

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Tokyo, Japan

Site JP00016

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Tokyo, Japan

Site JP00017

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Tokyo, Japan

Site JP00023

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Tokyo, Japan

Site JP00026

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Tokyo, Japan

Site JP00027

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Tokyo, Japan

Site JP00029

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Tokyo, Japan

Site JP00060

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Fukuoka, Japan

Site JP00024

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Tokyo, Japan

Site JP00059

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Hyogo, Japan

Site JP00004

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Aichi, Japan

Site JP00015

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Tokyo, Japan

Site JP00018

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Tokyo, Japan

Site JP00031

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Kanagawa, Japan

Site JP00003

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Osaka, Japan

Site JP00052

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Osaka, Japan

Site JP00049

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Aichi, Japan

Site JP00025

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Tokyo, Japan

Site JP00033

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Kanagawa, Japan

Site JP00051

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Osaka, Japan

Site JP00019

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Tokyo, Japan

Site JP00020

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Tokyo, Japan

Site JP00021

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Tokyo, Japan

Site JP00022

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Tokyo, Japan

Site JP00028

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Tokyo, Japan

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