Clinical trial NCT02809105: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Constipation
Keywords: Chronic constipation
Linaclotide
ASP0456
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2016-06-22
Enrollment: 186
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

  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

Primary outcomes:
measure: Change from baseline in weekly mean SBM frequency during one week of administration (Part I)
timeFrame: Baseline and Week 1
Secondary outcomes:
measure: Change from baseline in weekly mean SBM frequency
timeFrame: Baseline and up to Week 56
measure: Weekly responder rate of SBM
timeFrame: Baseline and up to Week 56
measure: Percentage of subjects with SBM within 24 hours after the start of the initial administration
timeFrame: Up to 24h
measure: Time to first SBM
timeFrame: Up to Week 4
measure: Change from baseline in weekly mean CSBM frequency
timeFrame: Baseline and up to Week 56
measure: Weekly responder rate of CSBM
timeFrame: Baseline and up to Week 56
measure: Percentage of subjects with CSBM within 24 hours after the start of the initial administration
timeFrame: Up to 24h
measure: Change from baseline in weekly mean stool form score
timeFrame: Baseline and up to Week 56
measure: Change from baseline in weekly mean abdominal bloating severity score
timeFrame: Baseline and up to Week 56
measure: Change from baseline in weekly mean abdominal pain/discomfort severity score
timeFrame: Baseline and up to Week 56
measure: Change from baseline in weekly mean straining severity score
timeFrame: Baseline and up to Week 56
measure: Weekly responder rate of global assessment of relief of CC symptoms
timeFrame: Up to Week 56
measure: Weekly responder rate of abnormal bowel habits improvement in CC
timeFrame: Up to Week 56
measure: Weekly responder rate of abdominal symptoms relief of CC
timeFrame: Up to Week 56
measure: Change from baseline in IBS-QOL-J score
timeFrame: Baseline and up to Week 56
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 56
measure: Number of participants with abnormal Vital signs and/or adverse events during treatment period
timeFrame: Up to Week 56
measure: Number of participants with abnormal Laboratory values and/or adverse events during treatment period
timeFrame: Up to Week 56
measure: Safety assessed by body weight
timeFrame: Up to Week 56
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00029
city: Aichi
country: Japan
facility: Site JP00030
city: Chiba
country: Japan
facility: Site JP00021
city: Chiba
country: Japan
facility: Site JP00022
city: Chiba
country: Japan
facility: Site JP00023
city: Chiba
country: Japan
facility: Site JP00024
city: Fukuoka
country: Japan
facility: Site JP00040
city: Hokkaido
country: Japan
facility: Site JP00001
city: Hokkaido
country: Japan
facility: Site JP00002
city: Hyogo
country: Japan
facility: Site JP00037
city: Hyogo
country: Japan
facility: Site JP00038
city: Hyogo
country: Japan
facility: Site JP00039
city: Kanagawa
country: Japan
facility: Site JP00017
city: Kanagawa
country: Japan
facility: Site JP00018
city: Kanagawa
country: Japan
facility: Site JP00019
city: Kanagawa
country: Japan
facility: Site JP00020
city: Osaka
country: Japan
facility: Site JP00031
city: Osaka
country: Japan
facility: Site JP00032
city: Osaka
country: Japan
facility: Site JP00033
city: Osaka
country: Japan
facility: Site JP00034
city: Osaka
country: Japan
facility: Site JP00035
city: Osaka
country: Japan
facility: Site JP00036
city: Saitama
country: Japan
facility: Site JP00025
city: Saitama
country: Japan
facility: Site JP00026
city: Saitama
country: Japan
facility: Site JP00027
city: Saitama
country: Japan
facility: Site JP00028
city: Tokyo
country: Japan
facility: Site JP00003
city: Tokyo
country: Japan
facility: Site JP00004
city: Tokyo
country: Japan
facility: Site JP00005
city: Tokyo
country: Japan
facility: Site JP00006
city: Tokyo
country: Japan
facility: Site JP00007
city: Tokyo
country: Japan
facility: Site JP00008
city: Tokyo
country: Japan
facility: Site JP00009
city: Tokyo
country: Japan
facility: Site JP00010
city: Tokyo
country: Japan
facility: Site JP00011
city: Tokyo
country: Japan
facility: Site JP00012
city: Tokyo
country: Japan
facility: Site JP00013
city: Tokyo
country: Japan
facility: Site JP00014
city: Tokyo
country: Japan
facility: Site JP00015
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: