Efficacy, Safety and Tolerability of DNK333 (25 and 100 mg Bid) in Women With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) (CDNK333B2201)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter 2-Week Pilot Study to Evaluate the Efficacy, Safety and Tolerability of DNK333 (25 and 100 mg Bid) Given Orally in Female Patients With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)

This study will evaluate the tolerability, safety and efficacy of DNK333 against diarrhea caused by Irritable Bowel Syndrome in women.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Drug: DNK333

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
    • Huntsville, Alabama, United States, 35801
    • Northport, Alabama, United States, 35476
  • Arizona
    • Tucson, Arizona, United States, 85712
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
  • California
    • Orange, California, United States, 92869
    • Riverside, California, United States, 92506
    • San Diego, California, United States, 92108
    • Torrance, California, United States, 90505
  • Connecticut
    • Bristol, Connecticut, United States, 06010
    • Hartford, Connecticut, United States, 06106
  • Florida
    • Hollywood, Florida, United States, 33021
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • Kansas
    • Arkansas City, Kansas, United States, 67005
  • Kentucky
    • Lexington, Kentucky, United States, 40504
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • Missouri
    • Mexico, Missouri, United States, 65265
    • Washington, Missouri, United States, 63090
  • Nebraska
    • Lincoln, Nebraska, United States, 68503
  • Ohio
    • Dayton, Ohio, United States, 45440
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
    • Tulsa, Oklahoma, United States, 74135
  • Pennsylvania
    • Beaver Falls, Pennsylvania, United States, 15010
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
    • Memphis, Tennessee, United States, 38119
    • Nashville, Tennessee, United States, 37205
  • Texas
    • Austin, Texas, United States, 78758
    • Lake Jackson, Texas, United States, 77566
  • Utah
    • Salt Lake City, Utah, United States, 84102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Women of 18 - 65 years of age with IBS-D as defined by the Rome II criteria. The Rome II criteria is a system used for diagnosing functional gastrointestinal disorders such as irritable bowel syndrome. It involves completing of a questionnaire about gastrointestinal symptoms.

Note: Patients who are 50 years of age and older must have had a colonoscopy OR a flexible sigmoidoscopy plus a double-contrast barium enema within the past 5 years, which demonstrated no clinically significant findings.

Clinically significant findings may include but are not limited to malignant tumors, multiple (≥3) or advanced adenomas, inflammatory bowel disease, diverticulitis, ischaemic colitis, lymphocytic colitis, or collagenous colitis.

Patients must report ≥ 3 days with IBS-related abdominal pain/discomfort plus at least 3 days of 2 or more of the following events during the baseline period:

1. ≥ 3 bowel movements/day
2. Bowel urgency

3. Loose or watery stool

   -

   Exclusion Criteria:

   • Patients who answer "yes" to either or both of the two weekly satisfaction questions during the baseline period. The questions are: (1) Over the past week did you have satisfactory relief of your IBS-related abdominal pain/discomfort? (2) Over the last week did you have satisfactory relief of your overall IBS-D symptoms?
   • Patients with hard or lumpy stools for more than one day during the baseline period
   • Lactose intolerant patients relieved on a lactose free diet
   • Use of antidepressants (tricyclic, SSRI etc), opioid analgesic drugs or drugs specifically affecting bowel motility during the course of the trial.
   • Women of child-bearing potential who do not use an acceptable methods of contraception
   • Pregnant or nursing (lactating) women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1	Drug: DNK333; 25 mg and 100 mg oral doses, each taken twice daily
EXPERIMENTAL: 2	Drug: DNK333; 25 mg and 100 mg oral doses, each taken twice daily
PLACEBO_COMPARATOR: 3	Drug: DNK333; 25 mg and 100 mg oral doses, each taken twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in average stool form score at 2 weeks	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in average score at week 1, week 2: Abdominal pain/discomfort, bloating; satisfaction with bowel habits; weekly stool frequency; percent of days with satisfactory control of bowel urgency; satisfactory relief of overall IBS symptoms	2 weeks

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Novartis

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): September 1, 2005
• Study Completion (ACTUAL): September 1, 2005

Study Registration Dates

• First Submitted: June 12, 2008
• First Submitted That Met QC Criteria: June 12, 2008
• First Posted (ESTIMATE): June 17, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 17, 2008
• Last Update Submitted That Met QC Criteria: June 12, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: Diarrhea; IBS; IBS-D; gastrointestinal functional disorder
• 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; Diarrhea
• Other Study ID Numbers: CDNK333B2201