The Efficacy of AZD1722 in Constipation Predominant Irritable Bowel Syndrome (IBS-C)

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of AZD1722 for the Treatment of Constipation-Predominant Irritable Bowel Syndrome (IBS-C)

This phase 2, randomized, double blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of three dose levels of AZD1722 in subjects with constipation predominant IBS (IBS-C) as defined by the ROME III criteria and who have active disease as determined during a two-week screening period. Subjects who qualify and are randomized into the study will receive 5, 20, or 50 mg of AZD1722 BID or placebo BID for 12 consecutive weeks. At the end of this treatment period, subjects will be followed for an additional 4 weeks.

Study Overview

• Status: Completed
• Conditions: Constipation Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: AZD1722

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States
  • North Carolina
    • Greensboro, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Tennessee
    • Chattanooga, Tennessee, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Females and males must agree to use appropriate methods of contraception or be sterile (with appropriate documentation)
• Subject is ambulatory
• Subject meets definition of IBS-C using Rome III Criteria for the Diagnosis of IBS with a history of <5 SBMs per week
• Subject meets Screening eligibility criteria (see below)
• A colonoscopy based on AGA guidelines; every 10 years at ≥ 50 years old, or the occurrence of any warning signs (i.e., unexplained weight loss, non-hemorrhoid blood in stools)
• Ability to communicate well with the Investigator and to comply with the requirements of the entire study, including an understanding of how to use the touch-tone telephone electronic diary.
• Written informed consent and a willingness to participate in the study as it is described.
• Daily access to a touch tone telephone.

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 or carcinoid syndrome.
• Use of medications that are known to affect stool consistency (Prohibited Medications), including fiber supplements, anti-diarrheals, cathartics, antacids, opiates, prokinetic drugs, laxatives, enemas, antibiotics within 4 weeks of enrollment, probiotics (including probiotic yogurt); or salt or electrolyte supplements containing sodium, potassium, chloride, or bicarbonate formulations during the seven days prior to treatment; unless specified as rescue medication, and used accordingly.
• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic, psychiatric or any disease that may interfere with the subject successfully completing the trial.
• The 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.
• Pregnant or lactating women.
• A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or other psychoses that has required hospitalization in the last 3 years. History of attempted suicide or uncontrolled bipolar disorder. Alcohol or substance abuse in the last year.
• Participation in other clinical trials within 1 month prior to Day -14 (beginning of screening period).
• If, in the opinion of the Investigator the subject is unable or unwilling to fulfill the requirements of the protocol or has a condition, which would render the results uninterpretable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
EXPERIMENTAL: 5 mg BID; AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor
EXPERIMENTAL: 20 mg BID; AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor
EXPERIMENTAL: 50 mg BID; AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Complete Spontaneous Bowel Movement Responders vs Placebo	Weekly complete spontaneous bowel movement resaponders defined as an increase of one or more bowel movement per week from baseline for 6 of the 12 weeks	12 weeks

Collaborators and Investigators

• Sponsor: Ardelyx

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: August 14, 2013
• First Posted (ESTIMATE): August 15, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation
• Other Study ID Numbers: D5612C00001