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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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) -

Conditions
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Chronic Constipation

Intervention / Treatment
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* Drug: linaclotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I ASP0456<br>ASP0456 will be administered orally for 4 weeks. | Drug: linaclotide<br>* Oral administration once daily<br>* Other names: ASP0456;|
| Placebo Comparator: Part I Placebo<br>Placebo will be administered orally for 4 weeks. | Drug: Placebo<br>* Oral administration once daily<br>|
| Experimental: Part II ASP0456<br>ASP0456 will be administered orally. | Drug: linaclotide<br>* Oral administration once daily<br>* Other names: ASP0456;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic constipation, Linaclotide, ASP0456