Clinical trial NCT01020708: Study of the Safety and Tolerability of ALTH12 Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis
Official title: A Phase I Double-blind, Randomized, Comparator-controlled Study of the Safety and Tolerability of N-acetylcysteine Plus Mesalamine Enema in Subjects With Left-sided Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: colitis
inflammatory bowel disease
ulcerative colitis
rectal administration
enema
mesalamine
Lead sponsor: Altheus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2009-11-24
Enrollment: 9
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 Phase I study will be a closely monitored trial of a small number of subjects to establish, preliminarily, the tolerability and safety of two ALTH12 enema formulations: ALTH12-1:4 and ALTH12-2:4. The study will be conducted in two parts. The first part will be the assessment of the safety and tolerability of a single dose of ALTH12-1:4 or the comparator, mesalamine (4.0g 5-ASA) followed by an assessment of repeated administrations of study drug (ALTH12-1:4 or comparator) for 6 weeks. The second part will be the same assessment for ALTH12-2:4. Three subjects will be enrolled in each cohort: 2 to receive ALTH12 enema therapy and 1 subject to receive comparator enema therapy. A total of up to 9 patients will be enrolled in this study, allowing for up to 3 replacement or additional patients.


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 active disease or disease in remission.
* Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI with a sigmoidoscopy score of 1 point or less and Physician's rating of disease score of 1 point or less (mild or remission).
* Laboratory data:

  1. White blood cell count between 4,500 and 10,000 cells/mL
  2. Platelet count: 150,000-450,000 cells/mL
  3. Hemoglobin \> 10.0 g/dL
  4. Total bilirubin \< 1.5 mg/dL
  5. Aspartate aminotransferase \< 100 u/dL
  6. Alanine aminotransferase \< 100 u/dL
  7. Alkaline phosphatase \< 250 u/dL
  8. Blood urine nitrogen \< 40 mg/dL
  9. Creatinine \< 1.5 mg/dL
  10. Amylase \< 150 U/L
* Satisfied one of the following:
* Female subjects of childbearing potential must have a negative serum 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:

Subjects will be excluded if:

* They have documented history of 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 2 or greater (moderate or severe disease) or an endoscopy score of 2 or greater.
* They have shown evidence of high grade dysplasia on 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.
* They have received systemic steroids or immunosuppressants within the previous 4 weeks.
* Treatment in the last 2 weeks that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) and/or 5-ASA enema (e.g. Rowasa®).
* 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 abuse.
* They have a known allergy to N-acetylcysteine or Mesalamine.
* 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.
* 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: To determine the safety and tolerability of ALTH12 when given by intrarectal administration over 6 weeks to subjects with ulcerative colitis (UC) involving the left side of the colon
timeFrame: 6 weeks treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research
state: Oklahoma
Study officials:
affiliation: Oklahoma Foundation for Digestive Research
name: Philip B Miner, M.D.
role: PRINCIPAL_INVESTIGATOR
References: