Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

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

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: 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.

Relevance to patient case: not relevant