Study of the Safety and Efficacy of Zoenasa® Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis

A Phase II Double-blind, Randomized, Comparator-controlled Study of the Safety and Efficacy of Zoenasa™ Rectal Gel (Mesalamine Plus N-acetylcysteine) in Subjects With Left-sided Ulcerative Colitis

This double-blind, randomized, comparator-controlled Phase II study is designed to establish the safety and efficacy of Zoenasa Rectal Gel compared to mesalamine enema in subjects with left-sided ulcerative colitis, as measured by the modified ulcerative colitis disease activity index (UCDAI), over 6 weeks of treatment. In this study, two cohorts of subjects will receive either Zoenasa-1:4 (1.0g NAC; 4.0g 5-ASA) investigational drug enema therapy or comparator mesalamine enema (4.0g 5-ASA). The study will enroll subjects randomized equally into the 2 cohorts. Each cohort will enroll approximately 60 subjects. The two arms of the trial will be enrolled concurrently in a randomized fashion.

Study Overview

• Status: Unknown
• Conditions: Ulcerative Colitis; Left-sided Ulcerative Colitis; Distal Ulcerative Colitis
• Intervention / Treatment: Drug: Zoenasa-1:4; Drug: Mesalamine Enema

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Birmingham Gastroenterology Associates
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
  • Colorado
    • Lakewood, Colorado, United States, 80214
      • Rocky Mountain Gastroenterology
  • Florida
    • Gainesville, Florida, United States, 32605
      • Digestive Disease Associates
    • Hialeah, Florida, United States, 33016
      • Digestive Medical Associates
    • Hollywood, Florida, United States, 33021
      • The Center for Gastrointestinal Disorders
    • Miami, Florida, United States, 33156
      • Miami Gastroenterology Consultants P.A.
    • Miami, Florida, United States, 33186
      • South Medical Research Group
    • Naples, Florida, United States, 34102
      • Gastroenterology of Naples
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology
  • Georgia
    • Athens, Georgia, United States, 30606
      • Tri-County Research
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
    • Decatur, Georgia, United States, 30033
      • The Atlanta Center For Gastroenterology
    • Savannah, Georgia, United States, 31405
      • St. Josephs Candler Health System
  • Illinois
    • Arlington Heights, Illinois, United States, 60004
      • NCH Medical Group
  • Iowa
    • Davenport, Iowa, United States, 52807
      • Gastrointestinal Clinic of Quad Cities
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management of Louisiana
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Dr. Jason Bozdin, M.D.
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Wyoming, Michigan, United States, 48418
      • Gregory Cammel, MD PLC
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • GI Associates and Endoscopy Center
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
    • New York, New York, United States, 10028
      • Research Associates of New York
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Davidson, North Carolina, United States, 28036
      • Carolina Digestive Health Associates
    • Greensboro, North Carolina, United States, 27403
      • LeBauer Research Associates, P.A.
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Greater Cincinnati Gastroenterology
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Central Sooner Research
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Foundation for Digestive Research
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research
    • Tulsa, Oklahoma, United States, 74135
      • Gastroenterology United Tulsa
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
    • Houston, Texas, United States, 77090
      • Houston Digestive Disease Clinic
    • Plano, Texas, United States, 75075
      • Digestive Health Associates of Texas
  • Utah
    • South Ogden, Utah, United States, 84405
      • Advanced Research Institute
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • New River Valley Research Institute
    • Norfolk, Virginia, United States, 23502
      • Digestive & Liver Disease Specialists
  • Washington
    • Seattle, Washington, United States, 98101
      • Digestive Disease Institute
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects are eligible if they are ≥ 18 years of age and ≤ 64 years.
• They have a documented history of idiopathic ulcerative colitis based on endoscopic and/or histologic findings involving the left side of the colon, with mild to moderate active disease.
• Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI score of 4-10, inclusive, with a Physician's rating of disease score of 2 points or less (mild or moderate active ulcerative colitis), rectal bleeding score of 1 or more (based on subject diary), and mucosal appearance score (based on endoscopy) of 1 point or more at baseline.

• Laboratory data:

  • White blood cell count between 4.0 - 12.0 K/mm3
  • Platelet count: 150 - 500 K/mm3
  • Hemoglobin > 10.0 g/dL
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase < 100 u/dL
  • Alanine aminotransferase < 100 u/dL
  • Alkaline phosphatase < 250 u/dL
  • Blood urine nitrogen < 40 mg/dL
  • Creatinine < 1.5 mg/dL
• Satisfies one of the following:
• Female subjects of childbearing potential must have a negative urine pregnancy test at screening; surgically sterile, post-menopausal, abstinent, or patient or partner agree to use a medically appropriate form of birth control from screening to until 1 month after the last dose of study medication.
• Male subjects must be surgically sterile, abstinent, or patient or partner compliant with a contraceptive regimen from screening to until 1 month after the last dose of study medication.
• They are able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.

Exclusion Criteria:

• They have documented history of proximal or universal ulcerative colitis, proctitis or active proctitis confined to 15cm or less from the anal verge.
• They demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis.
• They receive a Physician's rating of disease severity as part of the modified UCDAI of 3 (severe disease) or an aggregate score of 11 or greater.
• They have shown prior documented history of evidence of high grade dysplasia on biopsy from endoscopic examinations.
• Their stool contains enteric pathogens or Clostridium difficile toxins.
• They have a history of recurrent Clostridium difficile infection.
• They have prior history of biologic therapy within the previous 4 years.
• They have received systemic steroids or immunosuppressants within the previous 4 weeks.
• Treatment in the last 14 days that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) or mesalamine enema (Rowasa®).
• Treatment in the last 7 days that included mesalamine (5-ASA) via oral administration (e.g. Asacol®, Lialda®, balsalazide, etc).
• They have a history of cancer (defined as malignancy within 5 years except for squamous cell or basal cell cancers of the skin), asthma, or bronchospasm.
• Positive pregnancy test or lactating subjects.
• There is evidence of chemical substance abuse.
• They have had repeated anti-inflammatory drug treatment (longer than 3 days at doses that exceed those available without a prescription) within the previous 7 days (with exception of aspirin at doses of 325mg/day or less for prophylaxis of cardiac disease), or initiated new non-steroidal anti-inflammatory (NSAID) treatment within the last 30 days.
• They have a known allergy to N-acetylcysteine or mesalamine, or have a history of serious AEs related to their use (including, but not limited to pancreatitis or hepatitis).
• They have a history of failure to retain enemas.
• Other clinically significant diseases that could interfere with the protocol compliance appear. These would include clinically important hematological, renal, hepatic, metabolic, psychiatric, central nervous system (CNS), pulmonary or cardiovascular disease.
• Use of any investigational medication within the previous 90 days.
• Any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zoenasa-1:4	Drug: Zoenasa-1:4; Zoenasa Rectal Gel (4.0g mesalamine [5-ASA], 1.0g N-acetylcysteine [NAC]; 60ml)
Active Comparator: Mesalamine Enema	Drug: Mesalamine Enema; Mesalamine Rectal Suspension Enema (4.0g mesalamine [5-ASA], 60ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified UCDAI at 6 weeks	Change from baseline in the modified Ulcerative Colitis Disease Activity Index (modified UCDAI) score at the end of the 6 week treatment period of Zoenasa™ Rectal Gel compared with mesalamine	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified UCDAI at 3 weeks	Change from baseline in the modified Ulcerative Colitis Disease Activity Index (modified UCDAI) score at the end of the 3 week treatment period of Zoenasa™ Rectal Gel compared with mesalamine	3 weeks
Clinical and endoscopic remission rates at 6 weeks	Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline	6 weeks
Clinical and endoscopic remission rates at 3 weeks	Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline	3 weeks
Clinical improvement rate after 6 weeks		6 weeks
Clinical improvement rate after 3 weeks		3 weeks
Endoscopic improvement rate at 6 weeks		6 weeks
Endoscopic improvement rate at 3 weeks		3 weeks
Change from baseline in endoscopic appearance after 6 weeks		6 weeks
Change from baseline in endoscopic appearance after 3 weeks		3 weeks
Time to resolution of rectal bleeding		Up to 6 weeks
Relapse rates at 6 weeks		6 weeks

Collaborators and Investigators

• Sponsor: Altheus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Estimate): January 8, 2014
• Last Update Submitted That Met QC Criteria: January 7, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: ulcerative colitis; N-acetylcysteine; NAC; UC; enema; mesalamine; mesalazine; acetylcysteine; 5-aminosalicylic acid; 5-ASA; left-sided ulcerative colitis; distal ulcerative colitis; Zoenasa; rectal gel
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: ZA-201