Clinical trial NCT02425722: A Study to Evaluate Dose Responses of Efficacy and Safety of ASP0456 in Patient With Chronic Constipation
Official title: Phase II Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study in Patients With Chronic Constipation (Not Including Constipation Due to Organic Diseases)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Constipation
Keywords: linaclotide
ASP0456
chronic constipation
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-04-24
Enrollment: 383
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 investigate dose-responses of efficacy and safety of ASP0456 in patients with chronic constipation (diagnosed by Rome III criteria of functional constipation (FC), not including constipation due to organic diseases) compared to placebo and to find the appropriate dose for P3 study.

Detailed description: To determine optimum dose of ASP0456 for the patients with chronic constipation (not including constipation due to organic diseases) in Japan based on its efficacy and safety, multicentered, placebo-controlled, double-blind, parallel group comparative study will be conducted.

After two-week observation period, the patient who meets the primary registration criteria will be randomized to the one from five groups and will start treatment period. The patients will take once daily orally before the breakfast for two weeks.

Eligibility criteria: Inclusion Criteria:

* Patient who had SBM\* (Spontaneous bowel movement) less than 3 times per week, more than six months prior to the provisional registration

  * \*Defecation without procedure of laxative, suppository, enema, or stool extraction on the day or preceding day of the defecation
* Patient who was affected with one or more following symptoms before more than six months of provisional registration:

  * Straining during at least 25% of defecations
  * Lumpy or hard stools in at least 25% of defecations
  * Sensation of incomplete evacuation for at least 25% of defecations
* Loose stools are rarely present without the use of laxatives more than six months prior to the provisional registration.
* Patients who had pancolonoscopy or contrast enema (or sigmoidoscopy) after the onset of chronic constipation symptom and had no organic changes

Exclusion Criteria:

* Patient who has met IBS-C diagnostic criteria from Rome III more than six months prior to provisional registration. Meaning that patient who had recurrent abdominal pain or discomfort at least 3 days/month in last 3 months associated with two or more of the following, and patient who was affected with following IBS symptoms more than six months prior to the provisional registration:

  * Improvement with defecation
  * Onset associated with a change in frequency of stool
  * Onset associated with a change in form (appearance) of stool
* 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 evidence of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
* Patient with history or current evidence of ischemic colitis
* Patient currently affected by infectious enteritis
* Patient currently affected by hyperthyroidism or hypothyroidism
* Patient with apparent mechanical obstruction (i.e. patient with ileus caused by hernia)
* Patient with mega colon or mega rectum
* Patient currently affected by constipation due to anorectal dysfunction
* Patient currently affected by drug induced constipation.
* Patient with constipation due to other organic disease
* Patient currently affected by active peptic ulcer
* In the case of a female, 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 (however, patient who used or underwent restricted drug/therapy according to Protocol may be enrolled provisionally)
* Patient with history or current evidence of malignant tumor
* Patient currently affected by serious cardiovascular disease, respiratory disease, kidney disease, hepatic disease, gastrointestinal disease (excluding CC), hemorrhagic disease, or neural/mental disease
* Patient with history of drug allergy

Primary outcomes:
measure: Change in weekly average of SBM frequency
timeFrame: From baseline to week 1
Secondary outcomes:
measure: Weekly responder rate for SBM
timeFrame: up to 2 weeks
measure: Weekly responder rate for CSBM
timeFrame: up to 2 weeks
measure: Percentage of subjects with SBM within 24 hours after the start of initial treatment
timeFrame: up to 24 hours
measure: Change in weekly average of CSBM frequency
timeFrame: From baseline to week 1
measure: Proportion of subjects with CSBM within 24 hours after the start of initial treatment
timeFrame: up to 24 hours
measure: Weekly responder rate of the global assessment of relief of chronic constipation.
timeFrame: up to 2 weeks
measure: Weekly responder rate of the abdominal bowel habits improvement in chronic constipation.
timeFrame: up to 2 weeks
measure: Weekly responder rate of abdominal symptom relief of chronic constipation.
timeFrame: up to 2 weeks
measure: Score of the global assessment of relief of chronic constipation
timeFrame: up to 2 weeks
measure: Changes in IBS-QOL-J scores (entire scores or scores on the sub-scales)
timeFrame: Week 0, and 2
measure: Changes in weekly average of SBM frequency
timeFrame: From baseline to every week until 2 weeks
measure: Changes in weekly average of CSBM frequency
timeFrame: From baseline to every week until 2 weeks
measure: Changes in weekly average of stool form
timeFrame: From baseline to every week until 2 weeks
measure: Changes in weekly average of abdominal bloating severity scores
timeFrame: From baseline to every week until 2 weeks
measure: Changes in weekly average of abdominal pain/discomfort severity scores
timeFrame: From baseline to every week until 2 weeks
measure: Changes in weekly average of straining severity scores
timeFrame: From baseline to every week until 2 weeks
measure: Score of the abdominal bowel habits improvement in chronic constipation
timeFrame: up to 2 weeks
measure: Score of the abdominal symptom relief of chronic constipation
timeFrame: up to 2 weeks
measure: Safety assessed by development of incidence of adverse events, vital signs, clinical laboratory tests and body weight
timeFrame: up to 2 weeks
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site: 35
city: Aichi
country: Japan
facility: Site: 36
city: Chiba
country: Japan
facility: Site: 27
city: Chiba
country: Japan
facility: Site: 28
city: Chiba
country: Japan
facility: Site: 29
city: Chiba
country: Japan
facility: Site: 30
city: Fukuoka
country: Japan
facility: Site: 48
city: Fukuoka
country: Japan
facility: Site: 49
city: Fukuoka
country: Japan
facility: Site: 50
city: Hokkaido
country: Japan
facility: Site: 1
city: Hokkaido
country: Japan
facility: Site: 2
city: Hyogo
country: Japan
facility: Site: 45
city: Hyogo
country: Japan
facility: Site: 46
city: Hyogo
country: Japan
facility: Site: 47
city: Kanagawa
country: Japan
facility: Site: 22
city: Kanagawa
country: Japan
facility: Site: 23
city: Kanagawa
country: Japan
facility: Site: 24
city: Kanagawa
country: Japan
facility: Site: 25
city: Kanagawa
country: Japan
facility: Site: 26
city: Kyoto
country: Japan
facility: Site: 44
city: Osaka
country: Japan
facility: Site: 37
city: Osaka
country: Japan
facility: Site: 38
city: Osaka
country: Japan
facility: Site: 39
city: Osaka
country: Japan
facility: Site: 40
city: Osaka
country: Japan
facility: Site: 41
city: Osaka
country: Japan
facility: Site: 42
city: Osaka
country: Japan
facility: Site: 43
city: Saitama
country: Japan
facility: Site: 31
city: Saitama
country: Japan
facility: Site: 32
city: Saitama
country: Japan
facility: Site: 33
city: Saitama
country: Japan
facility: Site: 34
city: Tokyo
country: Japan
facility: Site: 10
city: Tokyo
country: Japan
facility: Site: 11
city: Tokyo
country: Japan
facility: Site: 12
city: Tokyo
country: Japan
facility: Site: 13
city: Tokyo
country: Japan
facility: Site: 14
city: Tokyo
country: Japan
facility: Site: 15
city: Tokyo
country: Japan
facility: Site: 16
city: Tokyo
country: Japan
facility: Site: 17
city: Tokyo
country: Japan
facility: Site: 18
city: Tokyo
country: Japan
facility: Site: 19
city: Tokyo
country: Japan
facility: Site: 20
city: Tokyo
country: Japan
facility: Site: 21
city: Tokyo
country: Japan
facility: Site: 3
city: Tokyo
country: Japan
facility: Site: 4
city: Tokyo
country: Japan
facility: Site: 5
city: Tokyo
country: Japan
facility: Site: 6
city: Tokyo
country: Japan
facility: Site: 7
city: Tokyo
country: Japan
facility: Site: 8
city: Tokyo
country: Japan
facility: Site: 9
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Fukudo S, Miwa H, Nakajima A, Kinoshita Y, Kosako M, Nakagawa A, Akiho H, Kuroishi K, Johnston JM, Currie M, Ohkusa T. Dose-finding study of linaclotide in Japanese patients with chronic constipation: A phase II randomized, double-blind, and placebo-controlled study. Neurogastroenterol Motil. 2018 Dec;30(12):e13442. doi: 10.1111/nmo.13442. Epub 2018 Aug 7.