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

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

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

Study Overview

• Status: Completed
• Conditions: Constipation-predominant Irritable Bowel Syndrome (IBS-C)
• Intervention / Treatment: Drug: placebo; Drug: linaclotide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 559
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hokkaido, Japan
  • Kansai, Japan
  • Kantou, Japan
  • Kyusyu, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo group; oral	Drug: placebo; oral
Experimental: ASP0456 lowest dose group; oral	Drug: linaclotide; oral; Other Names: ASP0456
Experimental: ASP0456 low dose group; oral	Drug: linaclotide; oral; Other Names: ASP0456
Experimental: ASP0456 middle dose group; oral	Drug: linaclotide; oral; Other Names: ASP0456
Experimental: ASP0456 high dose group; oral	Drug: linaclotide; oral; Other Names: ASP0456

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2012
• Primary Completion (Actual): December 7, 2013
• Study Completion (Actual): December 7, 2013

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (Estimated): October 26, 2012

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: constipation; linaclotide; ASP0456; irritable bowel syndrome (IBS)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: 0456-CL-0021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.