A 12-Week Study With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of IBS-C (T3MPO-1)

Ardelyx

Status and phase: Completed; Phase 3

Conditions: Constipation Predominant Irritable Bowel Syndrome

Treatments: Drug: Placebo; Drug: Tenapanor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02621892

TEN-01-301

Details and patient eligibility

About

This phase 3, 12-week, randomized, double-blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of tenapanor in subjects with constipation-predominant irritable bowel syndrome (IBS-C) as defined by the ROME III criteria and who have active disease as determined after a two-week screening period. Subjects who qualify and are randomized into the study will either receive 50mg BID of tenapanor or placebo BID for 12 week treatment period and then undergo a 4 week placebo controlled randomized withdrawal.

Full description

During the 12-week treatment period, subjects will record daily assessments including: frequency and timing of bowel movements; sensation and complete bowel emptying; consistency of bowel movements; degree of straining, worst abdominal pain, abdominal discomfort, abdominal bloating, abdominal fullness and abdominal cramping. Subjects will also record weekly assessments including: adequate relief of IBS severity, and constipation severity.

At the end of the 12-week treatment period, there will be a 4-week randomized withdrawal period in which subjects who complete the study in Tenapanor group will be randomized to either Tenapanor 50mg BID or placebo BID (1:1) and subjects who complete the study in the placebo group will be assigned to receive Tenapanor 50mg BID.

Enrollment: 606 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 to 75 years old
• Females must be of non-childbearing potential; If of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception.
• Males must agree to use an appropriate method of barrier contraception or have documented surgical sterilization
• Subject meets definition of IBS-C using Rome III Criteria for the Diagnosis of IBS
• A colonoscopy based on AGA guidelines; every 10 years at ≥ 50 years old, or the occurrence of any warning signs

Exclusion criteria

• Functional diarrhea as defined by Rome III criteria
• IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome III criteria
• Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening; including but not limited to cancer, inflammatory bowel disease, diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer, pancreatitis (within 12 months of screening), cholelithiasis, amyloidosis, ileus, non-controlled GERD, gastrointestinal obstruction, ischemic colitis or carcinoid syndrome.
• Subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician)
• Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine > 2mg/dL)
• Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year
• Any surgery on the stomach, small intestine or colon, excluding appendectomy or cholecystectomy (unless within 60 days of screening visit)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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606 participants in 2 patient groups, including a placebo group

50mg BID

Experimental group

Description:

Tenapanor

Treatment:

Drug: Tenapanor

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo