A Study to Evaluate Dose Responses of Efficacy and Safety of ASP0456 in Patient With Chronic Constipation

Astellas

Status and phase: Completed; Phase 2

Conditions: Chronic Constipation

Treatments: Drug: Placebo; Drug: ASP0456

Study type: Interventional

Funder types: Industry

Identifiers

NCT02425722

0456-CL-1021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 383 patients

Sex: All

Ages: 20 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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383 participants in 5 patient groups, including a placebo group

ASP0456 0.0625mg

Experimental group

Description:

oral

Treatment:

Drug: ASP0456

ASP0456 0.125mg

Experimental group

Description:

oral

Treatment:

Drug: ASP0456

ASP0456 0.25mg

Experimental group

Description:

oral

Treatment:

Drug: ASP0456

ASP0456 0.5mg

Experimental group

Description:

oral

Treatment:

Drug: ASP0456

Placebo group

Placebo Comparator group

Description:

oral

Treatment:

Drug: Placebo