Clinical trial NCT02316899: Phase III Study to Evaluate the Efficacy and Safety of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome
Official title: Phase III Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study and Long-term Study in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
Keywords: ASP0456
constipation
linaclotide
irritable bowel syndrome (IBS)
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-12-15
Enrollment: 500
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 evaluate the efficacy and safety of ASP0456 in patients with constipation predominant irritable bowel syndrome (IBS-C).

Detailed description: \<Period I (double-blind period)\> A multicenter, collaborative, double-blind, parallel comparative study is conducted using IBS-C patients as subjects to verify efficacy of ASP0456 and examine the safety. After the 2-week bowel habit observation period, subjects satisfying the primary enrollment criteria are randomly allocated to either ASP0456 group or placebo group, and orally administered the drug or placebo once daily before breakfast for 12 weeks.

\<Period II (non-blind period)\> A multicenter, collaborative, non-blind, non-controlled study is conducted to examine safety and efficacy of ASP0456 in long-term administration in IBS-C patients. After Period I, subjects satisfying the transfer criteria are orally administered ASP0456 once daily before breakfast for 40 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients who had abdominal pain or discomfort repeatedly for at least 3 days per month during the 3 months before screening examination associated with at least 2 out of the following 3 conditions: (1) Improvement with defecation; (2) Onset associated with a change in frequency of stool; and (3) Onset associated with a change in form (appearance) of stool, and had the above symptom (IBS symptom) 6 months or more before the screening examination period
* Patients with ≥ 25% of stools hard or lumpy (with each bowel movement occurring without antidiarrheal, laxative, suppository or enema) and \<25% of them loose (mushy) or watery during the 3 months before the screening examination
* Patients who had pancolonoscopy or contrast enema (or sigmoidoscopy) after the onset of IBS symptom and had no organic changes

Exclusion Criteria:

* Patient with history of surgical resection of stomach, gallbladder, small intestine, or large intestine (excluding resection of appendicitis and benign polyp)
* Patient with history or current affection of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
* Patient with history or current affection of ischemic colitis
* Patient currently affected by infectious enteritis
* Patient currently affected by hyperthyroidism or hypothyroidism
* Patient currently affected by active peptic ulcer
* In the case of a female patient, the one currently affected by endometriosis or uterine adenomyosis
* Patient with high depression or anxiety considered to influence drug evaluation
* Patient with history of abuse of drug or alcohol within a year before consent acquisition, or with current abuse
* Patient who used or underwent or will use or undergo drug/therapy/test prohibited to combine 3 days before the start of bowel habit observation period (Day -17) or thereafter
* Patient with history or current affection of malignant tumor
* Patient currently affected by serious cardiovascular disease, respiratory disease, kidney disease, hepatic disease, gastrointestinal disease (excluding IBS), hemorrhagic disease, or neural/mental disease
* Patient with history of drug allergy

Primary outcomes:
measure: Responder rate of Global assessment of relief of IBS symptoms during 12 weeks.
timeFrame: During 12 weeks
measure: Responder rate of CSBM during 12 weeks
timeFrame: During 12 weeks
Secondary outcomes:
measure: Responder rate of SBM during 12 weeks
timeFrame: During 12 weeks
measure: Responder rate of Abnormal bowel habits improvement during 12 weeks
timeFrame: During 12 weeks
measure: Responder rate of Abdominal pain/discomfort relief during 12 weeks
timeFrame: During 12 weeks
measure: Weekly responder rate of Global assessment of relief of IBS symptoms
timeFrame: Up to 52 weeks
measure: Weekly responder rate of CSBM
timeFrame: Up to 52 weeks
measure: Weekly responder rate of SBM
timeFrame: Up to 52 weeks
measure: Weekly responder rate of Abnormal bowel habits improvement
timeFrame: Up to 52 weeks
measure: Weekly responder rate of Abdominal pain/discomfort relief
timeFrame: Up to 52 weeks
measure: Changes in weekly average of SBM frequency, CSBM frequency, stool form scores, abdominal pain/discomfort severity, abdominal bloating severity, and straining severity.
timeFrame: From baseline to every week until 52 weeks
measure: Changes in IBS-QOL-J scores (entire scores or scores on the sub-scales)
timeFrame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 40, 52
measure: Percentage of subjects with SBM within 24 hours after start of the initial administration
timeFrame: Up to 24 hours
measure: Percentage of subjects with CSBM within 24 hours after start of the initial administration
timeFrame: Up to 24 hours
measure: Safety assessed by development of incidence of adverse events, vital signs, and clinical laboratory tests
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00004
city: Aichi
country: Japan
facility: Site JP00048
city: Aichi
country: Japan
facility: Site JP00049
city: Chiba
country: Japan
facility: Site JP00038
city: Chiba
country: Japan
facility: Site JP00039
city: Chiba
country: Japan
facility: Site JP00040
city: Chiba
country: Japan
facility: Site JP00041
city: Chiba
country: Japan
facility: Site JP00042
city: Fukuoka
country: Japan
facility: Site JP00002
city: Fukuoka
country: Japan
facility: Site JP00060
city: Fukuoka
country: Japan
facility: Site JP00061
city: Hokkaido
country: Japan
facility: Site JP00001
city: Hokkaido
country: Japan
facility: Site JP00006
city: Hokkaido
country: Japan
facility: Site JP00007
city: Hyogo
country: Japan
facility: Site JP00057
city: Hyogo
country: Japan
facility: Site JP00058
city: Hyogo
country: Japan
facility: Site JP00059
city: Kanagawa
country: Japan
facility: Site JP00030
city: Kanagawa
country: Japan
facility: Site JP00031
city: Kanagawa
country: Japan
facility: Site JP00032
city: Kanagawa
country: Japan
facility: Site JP00033
city: Kanagawa
country: Japan
facility: Site JP00034
city: Kanagawa
country: Japan
facility: Site JP00035
city: Kanagawa
country: Japan
facility: Site JP00036
city: Kanagawa
country: Japan
facility: Site JP00037
city: Kyoto
country: Japan
facility: Site JP00056
city: Osaka
country: Japan
facility: Site JP00003
city: Osaka
country: Japan
facility: Site JP00050
city: Osaka
country: Japan
facility: Site JP00051
city: Osaka
country: Japan
facility: Site JP00052
city: Osaka
country: Japan
facility: Site JP00053
city: Osaka
country: Japan
facility: Site JP00054
city: Osaka
country: Japan
facility: Site JP00055
city: Saitama
country: Japan
facility: Site JP00043
city: Saitama
country: Japan
facility: Site JP00044
city: Saitama
country: Japan
facility: Site JP00045
city: Saitama
country: Japan
facility: Site JP00046
city: Saitama
country: Japan
facility: Site JP00047
city: Tokyo
country: Japan
facility: Site JP00005
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
city: Tokyo
country: Japan
facility: Site JP00016
city: Tokyo
country: Japan
facility: Site JP00017
city: Tokyo
country: Japan
facility: Site JP00018
city: Tokyo
country: Japan
facility: Site JP00019
city: Tokyo
country: Japan
facility: Site JP00020
city: Tokyo
country: Japan
facility: Site JP00021
city: Tokyo
country: Japan
facility: Site JP00022
city: Tokyo
country: Japan
facility: Site JP00023
city: Tokyo
country: Japan
facility: Site JP00024
city: Tokyo
country: Japan
facility: Site JP00025
city: Tokyo
country: Japan
facility: Site JP00026
city: Tokyo
country: Japan
facility: Site JP00027
city: Tokyo
country: Japan
facility: Site JP00028
city: Tokyo
country: Japan
facility: Site JP00029
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Fukudo S, Miwa H, Nakajima A, Haruma K, Kosako M, Nakagawa A, Akiho H, Yamaguchi Y, Johnston JM, Currie M, Kinoshita Y. A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan. Neurogastroenterol Motil. 2018 Dec;30(12):e13444. doi: 10.1111/nmo.13444. Epub 2018 Aug 22.