A Study of Oral Dosing of ASP0456 in Patients With Chronic Constipation

Phase 3 Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study and an Open-label, Uncontrolled, Long-term Dosing Study in Patients With Chronic Constipation (Not Including Constipation Due to Organic Diseases) -

The objective of this study is to verify the efficacy and investigate the safety of the study drug when ASP0456 is administered orally for 4 weeks and 52 weeks.

Study Overview

• Status: Completed
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: linaclotide; Drug: Placebo

Detailed Description

This study consists of two parts. In Part I, ASP0456 or placebo will be administered orally in a blind manner. In Part II, the long-term safety and efficacy of ASP0456 will be evaluated in patients who have participated in the study and completed the Part I.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site JP00030
  • Aichi, Japan
    • Site JP00029
  • Chiba, Japan
    • Site JP00021
  • Chiba, Japan
    • Site JP00022
  • Chiba, Japan
    • Site JP00023
  • Chiba, Japan
    • Site JP00024
  • Fukuoka, Japan
    • Site JP00040
  • Hokkaido, Japan
    • Site JP00001
  • Hokkaido, Japan
    • Site JP00002
  • Hyogo, Japan
    • Site JP00037
  • Hyogo, Japan
    • Site JP00038
  • Hyogo, Japan
    • Site JP00039
  • Kanagawa, Japan
    • Site JP00017
  • Kanagawa, Japan
    • Site JP00018
  • Kanagawa, Japan
    • Site JP00019
  • Kanagawa, Japan
    • Site JP00020
  • Osaka, Japan
    • Site JP00033
  • Osaka, Japan
    • Site JP00034
  • Osaka, Japan
    • Site JP00031
  • Osaka, Japan
    • Site JP00032
  • Osaka, Japan
    • Site JP00035
  • Osaka, Japan
    • Site JP00036
  • Saitama, Japan
    • Site JP00025
  • Saitama, Japan
    • Site JP00026
  • Saitama, Japan
    • Site JP00027
  • Saitama, Japan
    • Site JP00028
  • Tokyo, Japan
    • Site JP00006
  • Tokyo, Japan
    • Site JP00011
  • Tokyo, Japan
    • Site JP00012
  • Tokyo, Japan
    • Site JP00014
  • Tokyo, Japan
    • Site JP00010
  • Tokyo, Japan
    • Site JP00013
  • Tokyo, Japan
    • Site JP00015
  • Tokyo, Japan
    • Site JP00003
  • Tokyo, Japan
    • Site JP00004
  • Tokyo, Japan
    • Site JP00005
  • Tokyo, Japan
    • Site JP00007
  • Tokyo, Japan
    • Site JP00008
  • Tokyo, Japan
    • Site JP00009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with SBM frequency for < 3 times/week, since ≥ 6 months prior to preliminary enrollment
• Patients with one or more related symptoms for ≥ 6 months prior to preliminary enrollment
• Patients at whom loose (mushy) or watery stools are rarely present without the use of laxatives for ≥ 6 months prior to preliminary enrollment
• Patients who underwent pancolonoscopy or contrast enema after development of the CC symptoms and within 5 years prior to preliminary enrollment, and in whom no organic change was observed which dose not influence on CC symptoms
• Female patients must be either:

If of non-childbearing potential:

• Post-menopausal at the preliminary enrollment, or documented surgically sterile Or, if of childbearing potential,
• Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
• And have a negative urine pregnancy test at screening

• And, if heterosexually active, agree to consistently use two forms of highly effective birth control throughout the study period and for 28 days after the final study drug administration

  • Female patients must agree not to breastfeed throughout the study period and for 28 days after the final study drug administration
  • Female patients must not donate ova starting throughout the study period and for 28 days after the final study drug administration
  • Male subject and their female spouse/partners who are of childbearing potential must be using two forms of highly effective form of birth control starting at Screening and continue throughout the study period, and for 28 days after the final study drug administration
  • Male subject must not donate sperm starting at Screening and throughout the study period and, for 28 days after the final study drug administration

Exclusion Criteria:

• Patients who have met the Rome III diagnostic criteria for IBS; with recurrent abdominal pain or discomfort for ≥ 3 days/month in the last 3 months prior to preliminary enrollment, associated with ≥ 2 of the 3 characteristics described below and with the symptoms (IBS symptoms) described above for ≥ 6 months prior to preliminary enrollment

  1. Improvement with defecation
  2. Onset associated with a change in frequency of stool
  3. Onset associated with a change in form (appearance) of stool
• Patients with a history of surgical resection of the stomach, gallbladder, small intestine, or large intestine
• Patients with a history or current evidence of inflammatory bowel disease or ischemic colitis
• Patients with concurrent infectious enteritis, hyperthyroidism or hypothyroidism, constipation due to anorectal dysfunction, drug-induced constipation, constipation due to other organic diseases or active peptic ulcer
• Patients with apparent mechanical obstruction
• Patients with megacolon or megarectum
• For female patients, patients with concurrent endometriosis or adenomyosis
• Patients who are considered to have severe depression or a severe anxiety disorder that can affect the efficacy evaluation of the study drug
• Patients with a history of abuse of drugs or alcohol, or current abuse of drugs or alcohol
• Patients who used/underwent or are scheduled to use/undergo prohibited concomitant drugs or therapies, or in whom prohibited examinations were conducted or are scheduled to be conducted 3 days prior to the start of the bowel habit observation period
• Patients with a history or current evidence of malignant tumors
• Patients with concurrent serious cardiovascular diseases, respiratory diseases, renal diseases, hepatic diseases, gastrointestinal disorders, blood diseases, or neurological/psychiatric diseases
• Patients with a history of drug allergies
• Patients who have participated in the clinical trial of ASP0456 or have been administered ASP0456
• Patients who have participated or are participating in another clinical trial or post-marketing clinical study of other ethical drugs or medical devices within 12 weeks prior to obtaining informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I ASP0456; ASP0456 will be administered orally for 4 weeks.	Drug: linaclotide; Oral administration once daily; Other Names: ASP0456
Placebo Comparator: Part I Placebo; Placebo will be administered orally for 4 weeks.	Drug: Placebo; Oral administration once daily
Experimental: Part II ASP0456; ASP0456 will be administered orally.	Drug: linaclotide; Oral administration once daily; Other Names: ASP0456

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in weekly mean SBM frequency during one week of administration (Part I)	SBM: Spontaneous bowel movement	Baseline and Week 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in weekly mean SBM frequency		Baseline and up to Week 56
Weekly responder rate of SBM	The weekly average 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.	Baseline and up to Week 56
Percentage of subjects with SBM within 24 hours after the start of the initial administration		Up to 24h
Time to first SBM		Up to Week 4
Change from baseline in weekly mean CSBM frequency	CSBM: SBM without a sensation of incomplete evacuation	Baseline and up to Week 56
Weekly responder rate of CSBM	The weekly average 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.	Baseline and up to Week 56
Percentage of subjects with CSBM within 24 hours after the start of the initial administration		Up to 24h
Change from baseline in weekly mean stool form score	Stool form will be measured using seven-point Bristol Stool Form Scale.	Baseline and up to Week 56
Change from baseline in weekly mean abdominal bloating severity score	Abdominal bloating severity will be measured using a five-point ordinal score.	Baseline and up to Week 56
Change from baseline in weekly mean abdominal pain/discomfort severity score	Abdominal pain/discomfort severity will be measured using a five-point ordinal score.	Baseline and up to Week 56
Change from baseline in weekly mean straining severity score	Straining severity will be measured using a five-point ordinal score.	Baseline and up to Week 56
Weekly responder rate of global assessment of relief of CC symptoms	CC: chronic constipation; The weekly responder of the evaluation items shall be the subject satisfying the following at the time of evaluation in each week: Score of Global assessment of relief of chronic constipation symptoms (7 scores: 1-7) is 1 or 2.	Up to Week 56
Weekly responder rate of abnormal bowel habits improvement in CC	Score of abdominal bowel habits improvement effect (7 scores: 1-7) is 1 or 2.	Up to Week 56
Weekly responder rate of abdominal symptoms relief of CC	Score of abdominal symptom improvement effect (7 scores: 1-7) is 1 or 2.	Up to Week 56
Change from baseline in IBS-QOL-J score	IBS-QOL-J: Japanese version of Irritable Bowel Syndrome Quality of Life	Baseline and up to Week 56
Safety assessed by incidence of adverse events		Up to Week 56
Number of participants with abnormal Vital signs and/or adverse events during treatment period		Up to Week 56
Number of participants with abnormal Laboratory values and/or adverse events during treatment period		Up to Week 56
Safety assessed by body weight		Up to Week 56

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2016
• Primary Completion (Actual): November 14, 2016
• Study Completion (Actual): November 10, 2017

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Chronic constipation; Linaclotide; ASP0456
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: 0456-CL-1031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No