Clinical trial NCT01586533: Study of the Safety and Efficacy of Zoenasa® Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ulcerative Colitis
Left-sided Ulcerative Colitis
Distal Ulcerative Colitis
Keywords: ulcerative colitis
UC
left-sided ulcerative colitis
distal ulcerative colitis
Zoenasa
mesalamine
mesalazine
5-ASA
5-aminosalicylic acid
N-acetylcysteine
acetylcysteine
NAC
enema
rectal gel
Lead sponsor: Altheus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in modified UCDAI at 6 weeks
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in modified UCDAI at 3 weeks
timeFrame: 3 weeks
measure: Clinical and endoscopic remission rates at 6 weeks
timeFrame: 6 weeks
measure: Clinical and endoscopic remission rates at 3 weeks
timeFrame: 3 weeks
measure: Clinical improvement rate after 6 weeks
timeFrame: 6 weeks
measure: Clinical improvement rate after 3 weeks
timeFrame: 3 weeks
measure: Endoscopic improvement rate at 6 weeks
timeFrame: 6 weeks
measure: Endoscopic improvement rate at 3 weeks
timeFrame: 3 weeks
measure: Change from baseline in endoscopic appearance after 6 weeks
timeFrame: 6 weeks
measure: Change from baseline in endoscopic appearance after 3 weeks
timeFrame: 3 weeks
measure: Time to resolution of rectal bleeding
timeFrame: Up to 6 weeks
measure: Relapse rates at 6 weeks
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Associates
state: Alabama
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Lakewood
country: United States
facility: Rocky Mountain Gastroenterology
state: Colorado
city: Gainesville
country: United States
facility: Digestive Disease Associates
state: Florida
city: Hialeah
country: United States
facility: Digestive Medical Associates
state: Florida
city: Hollywood
country: United States
facility: The Center for Gastrointestinal Disorders
state: Florida
city: Miami
country: United States
facility: Miami Gastroenterology Consultants P.A.
state: Florida
city: Miami
country: United States
facility: South Medical Research Group
state: Florida
city: Naples
country: United States
facility: Gastroenterology of Naples
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology
state: Florida
city: Athens
country: United States
facility: Tri-County Research
state: Georgia
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Decatur
country: United States
facility: The Atlanta Center for Gastroenterology
state: Georgia
city: Savannah
country: United States
facility: St. Josephs Candler Health System
state: Georgia
city: Arlington Heights
country: United States
facility: NCH Medical Group
state: Illinois
city: Davenport
country: United States
facility: Gastrointestinal Clinic of Quad Cities
state: Iowa
city: Wichita
country: United States
facility: Professional Research Network of Kansas
state: Kansas
city: Metairie
country: United States
facility: Clinical Trials Management of Louisiana
state: Louisiana
city: Berkley
country: United States
facility: Dr. Jason Bozdin, M.D.
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Wyoming
country: United States
facility: Gregory Cammel, MD PLC
state: Michigan
city: Jackson
country: United States
facility: GI Associates and Endoscopy Center
state: Mississippi
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: New York
country: United States
facility: Research Associates of New York
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Davidson
country: United States
facility: Carolina Digestive Health Associates
state: North Carolina
city: Greensboro
country: United States
facility: LeBauer Research Associates, P.A.
state: North Carolina
city: Cincinnati
country: United States
facility: Greater Cincinnati Gastroenterology
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Tulsa
country: United States
facility: Gastroenterology United Tulsa
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Digestive Disease Clinic
state: Texas
city: Plano
country: United States
facility: Digestive Health Associates of Texas
state: Texas
city: South Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Christiansburg
country: United States
facility: New River Valley Research Institute
state: Virginia
city: Norfolk
country: United States
facility: Digestive & Liver Disease Specialists
state: Virginia
city: Seattle
country: United States
facility: Digestive Disease Institute
state: Washington
city: Tacoma
country: United States
facility: Franciscan Research Center
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
Study officials:
References: