Back to resultsA Study of Oral Dosing of ASP0456 in Patients With Chronic Constipation
Primary Purpose
Chronic Constipation
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
linaclotide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Constipation focused on measuring Chronic constipation, Linaclotide, ASP0456
Eligibility Criteria
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
- Improvement with defecation
- Onset associated with a change in frequency of stool
- 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
Sites / Locations
- Site JP00029
- Site JP00030
- Site JP00021
- Site JP00022
- Site JP00023
- Site JP00024
- Site JP00040
- Site JP00001
- Site JP00002
- Site JP00037
- Site JP00038
- Site JP00039
- Site JP00017
- Site JP00018
- Site JP00019
- Site JP00020
- Site JP00031
- Site JP00032
- Site JP00033
- Site JP00034
- Site JP00035
- Site JP00036
- Site JP00025
- Site JP00026
- Site JP00027
- Site JP00028
- Site JP00003
- Site JP00004
- Site JP00005
- Site JP00006
- Site JP00007
- Site JP00008
- Site JP00009
- Site JP00010
- Site JP00011
- Site JP00012
- Site JP00013
- Site JP00014
- Site JP00015
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Part I ASP0456
Part I Placebo
Part II ASP0456
Arm Description
ASP0456 will be administered orally for 4 weeks.
Placebo will be administered orally for 4 weeks.
ASP0456 will be administered orally.
Outcomes
Primary Outcome Measures
Change from baseline in weekly mean SBM frequency during one week of administration (Part I)
SBM: Spontaneous bowel movement
Secondary Outcome Measures
Change from baseline in weekly mean SBM frequency
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.
Percentage of subjects with SBM within 24 hours after the start of the initial administration
Time to first SBM
Change from baseline in weekly mean CSBM frequency
CSBM: SBM without a sensation of incomplete evacuation
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.
Percentage of subjects with CSBM within 24 hours after the start of the initial administration
Change from baseline in weekly mean stool form score
Stool form will be measured using seven-point Bristol Stool Form Scale.
Change from baseline in weekly mean abdominal bloating severity score
Abdominal bloating severity will be measured using a five-point ordinal score.
Change from baseline in weekly mean abdominal pain/discomfort severity score
Abdominal pain/discomfort severity will be measured using a five-point ordinal score.
Change from baseline in weekly mean straining severity score
Straining severity will be measured using a five-point ordinal score.
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.
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.
Weekly responder rate of abdominal symptoms relief of CC
Score of abdominal symptom improvement effect (7 scores: 1-7) is 1 or 2.
Change from baseline in IBS-QOL-J score
IBS-QOL-J: Japanese version of Irritable Bowel Syndrome Quality of Life
Safety assessed by incidence of adverse events
Number of participants with abnormal Vital signs and/or adverse events during treatment period
Number of participants with abnormal Laboratory values and/or adverse events during treatment period
Safety assessed by body weight
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02809105
Brief Title
A Study of Oral Dosing of ASP0456 in Patients With Chronic Constipation
Official Title
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) -
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
June 24, 2016 (Actual)
Primary Completion Date
November 14, 2016 (Actual)
Study Completion Date
November 10, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Constipation
Keywords
Chronic constipation, Linaclotide, ASP0456
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
186 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part I ASP0456
Arm Type
Experimental
Arm Description
ASP0456 will be administered orally for 4 weeks.
Arm Title
Part I Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered orally for 4 weeks.
Arm Title
Part II ASP0456
Arm Type
Experimental
Arm Description
ASP0456 will be administered orally.
Intervention Type
Drug
Intervention Name(s)
linaclotide
Other Intervention Name(s)
ASP0456
Intervention Description
Oral administration once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration once daily
Primary Outcome Measure Information:
Title
Change from baseline in weekly mean SBM frequency during one week of administration (Part I)
Description
SBM: Spontaneous bowel movement
Time Frame
Baseline and Week 1
Secondary Outcome Measure Information:
Title
Change from baseline in weekly mean SBM frequency
Time Frame
Baseline and up to Week 56
Title
Weekly responder rate of SBM
Description
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.
Time Frame
Baseline and up to Week 56
Title
Percentage of subjects with SBM within 24 hours after the start of the initial administration
Time Frame
Up to 24h
Title
Time to first SBM
Time Frame
Up to Week 4
Title
Change from baseline in weekly mean CSBM frequency
Description
CSBM: SBM without a sensation of incomplete evacuation
Time Frame
Baseline and up to Week 56
Title
Weekly responder rate of CSBM
Description
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.
Time Frame
Baseline and up to Week 56
Title
Percentage of subjects with CSBM within 24 hours after the start of the initial administration
Time Frame
Up to 24h
Title
Change from baseline in weekly mean stool form score
Description
Stool form will be measured using seven-point Bristol Stool Form Scale.
Time Frame
Baseline and up to Week 56
Title
Change from baseline in weekly mean abdominal bloating severity score
Description
Abdominal bloating severity will be measured using a five-point ordinal score.
Time Frame
Baseline and up to Week 56
Title
Change from baseline in weekly mean abdominal pain/discomfort severity score
Description
Abdominal pain/discomfort severity will be measured using a five-point ordinal score.
Time Frame
Baseline and up to Week 56
Title
Change from baseline in weekly mean straining severity score
Description
Straining severity will be measured using a five-point ordinal score.
Time Frame
Baseline and up to Week 56
Title
Weekly responder rate of global assessment of relief of CC symptoms
Description
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.
Time Frame
Up to Week 56
Title
Weekly responder rate of abnormal bowel habits improvement in CC
Description
Score of abdominal bowel habits improvement effect (7 scores: 1-7) is 1 or 2.
Time Frame
Up to Week 56
Title
Weekly responder rate of abdominal symptoms relief of CC
Description
Score of abdominal symptom improvement effect (7 scores: 1-7) is 1 or 2.
Time Frame
Up to Week 56
Title
Change from baseline in IBS-QOL-J score
Description
IBS-QOL-J: Japanese version of Irritable Bowel Syndrome Quality of Life
Time Frame
Baseline and up to Week 56
Title
Safety assessed by incidence of adverse events
Time Frame
Up to Week 56
Title
Number of participants with abnormal Vital signs and/or adverse events during treatment period
Time Frame
Up to Week 56
Title
Number of participants with abnormal Laboratory values and/or adverse events during treatment period
Time Frame
Up to Week 56
Title
Safety assessed by body weight
Time Frame
Up to Week 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Improvement with defecation
Onset associated with a change in frequency of stool
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Inc
Official's Role
Study Director
Facility Information:
Facility Name
Site JP00029
City
Aichi
Country
Japan
Facility Name
Site JP00030
City
Aichi
Country
Japan
Facility Name
Site JP00021
City
Chiba
Country
Japan
Facility Name
Site JP00022
City
Chiba
Country
Japan
Facility Name
Site JP00023
City
Chiba
Country
Japan
Facility Name
Site JP00024
City
Chiba
Country
Japan
Facility Name
Site JP00040
City
Fukuoka
Country
Japan
Facility Name
Site JP00001
City
Hokkaido
Country
Japan
Facility Name
Site JP00002
City
Hokkaido
Country
Japan
Facility Name
Site JP00037
City
Hyogo
Country
Japan
Facility Name
Site JP00038
City
Hyogo
Country
Japan
Facility Name
Site JP00039
City
Hyogo
Country
Japan
Facility Name
Site JP00017
City
Kanagawa
Country
Japan
Facility Name
Site JP00018
City
Kanagawa
Country
Japan
Facility Name
Site JP00019
City
Kanagawa
Country
Japan
Facility Name
Site JP00020
City
Kanagawa
Country
Japan
Facility Name
Site JP00031
City
Osaka
Country
Japan
Facility Name
Site JP00032
City
Osaka
Country
Japan
Facility Name
Site JP00033
City
Osaka
Country
Japan
Facility Name
Site JP00034
City
Osaka
Country
Japan
Facility Name
Site JP00035
City
Osaka
Country
Japan
Facility Name
Site JP00036
City
Osaka
Country
Japan
Facility Name
Site JP00025
City
Saitama
Country
Japan
Facility Name
Site JP00026
City
Saitama
Country
Japan
Facility Name
Site JP00027
City
Saitama
Country
Japan
Facility Name
Site JP00028
City
Saitama
Country
Japan
Facility Name
Site JP00003
City
Tokyo
Country
Japan
Facility Name
Site JP00004
City
Tokyo
Country
Japan
Facility Name
Site JP00005
City
Tokyo
Country
Japan
Facility Name
Site JP00006
City
Tokyo
Country
Japan
Facility Name
Site JP00007
City
Tokyo
Country
Japan
Facility Name
Site JP00008
City
Tokyo
Country
Japan
Facility Name
Site JP00009
City
Tokyo
Country
Japan
Facility Name
Site JP00010
City
Tokyo
Country
Japan
Facility Name
Site JP00011
City
Tokyo
Country
Japan
Facility Name
Site JP00012
City
Tokyo
Country
Japan
Facility Name
Site JP00013
City
Tokyo
Country
Japan
Facility Name
Site JP00014
City
Tokyo
Country
Japan
Facility Name
Site JP00015
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.clinicalstudydatarequest.com
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=280
Description
Link to results on the Astellas Clinical Study Results website
Learn more about this trial
A Study of Oral Dosing of ASP0456 in Patients With Chronic Constipation
We'll reach out to this number within 24 hrs