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

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01586533
• Other study ID #: ZA-201
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 25, 2012
• Last updated: January 7, 2014
• Start date: June 2012

Study information

• Verified date: January 2014
• Source: Altheus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Distal Ulcerative Colitis
• Left-sided Ulcerative Colitis
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Zoenasa-1:4
Zoenasa Rectal Gel (4.0g mesalamine [5-ASA], 1.0g N-acetylcysteine [NAC]; 60ml)
• Mesalamine Enema
Mesalamine Rectal Suspension Enema (4.0g mesalamine [5-ASA], 60ml)

Locations

Country	Name	City	State
United States	NCH Medical Group	Arlington Heights	Illinois
United States	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina
United States	Tri-County Research	Athens	Georgia
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	Dr. Jason Bozdin, M.D.	Berkley	Michigan
United States	Birmingham Gastroenterology Associates	Birmingham	Alabama
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	New River Valley Research Institute	Christiansburg	Virginia
United States	Greater Cincinnati Gastroenterology	Cincinnati	Ohio
United States	Dallas VA Medical Center	Dallas	Texas
United States	Gastrointestinal Clinic of Quad Cities	Davenport	Iowa
United States	Carolina Digestive Health Associates	Davidson	North Carolina
United States	The Atlanta Center for Gastroenterology	Decatur	Georgia
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Digestive Disease Associates	Gainesville	Florida
United States	Gastro One	Germantown	Tennessee
United States	Memphis Gastroenterology Group	Germantown	Tennessee
United States	Long Island Clinical Research Associates	Great Neck	New York
United States	LeBauer Research Associates, P.A.	Greensboro	North Carolina
United States	Digestive Medical Associates	Hialeah	Florida
United States	The Center for Gastrointestinal Disorders	Hollywood	Florida
United States	Houston Digestive Disease Clinic	Houston	Texas
United States	GI Associates and Endoscopy Center	Jackson	Mississippi
United States	Rocky Mountain Gastroenterology	Lakewood	Colorado
United States	Clinical Trials Management of Louisiana	Metairie	Louisiana
United States	Miami Gastroenterology Consultants P.A.	Miami	Florida
United States	South Medical Research Group	Miami	Florida
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	Gastroenterology of Naples	Naples	Florida
United States	Research Associates of New York	New York	New York
United States	Digestive & Liver Disease Specialists	Norfolk	Virginia
United States	Central Sooner Research	Norman	Oklahoma
United States	Oklahoma Foundation for Digestive Research	Oklahoma City	Oklahoma
United States	Advanced Gastroenterology Associates	Palm Harbor	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Digestive Health Associates of Texas	Plano	Texas
United States	St. Josephs Candler Health System	Savannah	Georgia
United States	Digestive Disease Institute	Seattle	Washington
United States	Advanced Research Institute	South Ogden	Utah
United States	Franciscan Research Center	Tacoma	Washington
United States	Gastroenterology United Tulsa	Tulsa	Oklahoma
United States	Options Health Research	Tulsa	Oklahoma
United States	Professional Research Network of Kansas	Wichita	Kansas
United States	Shafran Gastroenterology	Winter Park	Florida
United States	Gregory Cammel, MD PLC	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Altheus Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Clinical and endoscopic remission rates at 6 weeks	Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline	6 weeks	No
Secondary	Clinical and endoscopic remission rates at 3 weeks	Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline	3 weeks	No
Secondary	Clinical improvement rate after 6 weeks		6 weeks	No
Secondary	Clinical improvement rate after 3 weeks		3 weeks	No
Secondary	Endoscopic improvement rate at 6 weeks		6 weeks	No
Secondary	Endoscopic improvement rate at 3 weeks		3 weeks	No
Secondary	Change from baseline in endoscopic appearance after 6 weeks		6 weeks	No
Secondary	Change from baseline in endoscopic appearance after 3 weeks		3 weeks	No
Secondary	Time to resolution of rectal bleeding		Up to 6 weeks	No
Secondary	Relapse rates at 6 weeks		6 weeks	Yes