Phase III Study to Evaluate the Efficacy and Safety of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome

Astellas

Status and phase: Completed; Phase 3

Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)

Treatments: Drug: linaclotide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02316899

0456-CL-0031

Details and patient eligibility

About

The objective of this study is to evaluate the efficacy and safety of ASP0456 in patients with constipation predominant irritable bowel syndrome (IBS-C).

Full 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.

Enrollment: 500 patients

Sex: All

Ages: 20 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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500 participants in 3 patient groups, including a placebo group

ASP0456 (Period I)

Experimental group

Description:

Up to 12 weeks

Treatment:

Drug: linaclotide

Placebo (Period I)

Placebo Comparator group

Description:

Up to 12 weeks

Treatment:

Drug: Placebo

ASP0456 (Period II)

Experimental group

Description:

From 12 weeks to 52 weeks

Treatment:

Drug: linaclotide