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

Chronic Constipation Clinical Trial

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) -

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02809105
• Other study ID #: 0456-CL-1031
• Status: Completed
• Phase: Phase 3
• Start date: June 24, 2016
• Est. completion date: November 10, 2017

Study information

• Verified date: December 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: November 10, 2017
• Est. primary completion date: November 14, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Constipation
• Constipation

Intervention

Drug:
• linaclotide
Oral administration once daily
• Placebo
Oral administration once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in weekly mean SBM frequency during one week of administration (Part I)	SBM: Spontaneous bowel movement	Baseline and Week 1
Secondary	Change from baseline in weekly mean SBM frequency		Baseline and up to Week 56
Secondary	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
Secondary	Percentage of subjects with SBM within 24 hours after the start of the initial administration		Up to 24h
Secondary	Time to first SBM		Up to Week 4
Secondary	Change from baseline in weekly mean CSBM frequency	CSBM: SBM without a sensation of incomplete evacuation	Baseline and up to Week 56
Secondary	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
Secondary	Percentage of subjects with CSBM within 24 hours after the start of the initial administration		Up to 24h
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Safety assessed by incidence of adverse events		Up to Week 56
Secondary	Number of participants with abnormal Vital signs and/or adverse events during treatment period		Up to Week 56
Secondary	Number of participants with abnormal Laboratory values and/or adverse events during treatment period		Up to Week 56
Secondary	Safety assessed by body weight		Up to Week 56

External Links

•   Link to results on the Astellas Clinical Study Results website