Ulcerative Colitis
Conditions
Keywords
colitis, inflammatory bowel disease, ulcerative colitis, rectal administration, enema, mesalamine
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.
Interventions
DRUGmesalamine
4.0g mesalamine rectal suspension, rectally administered enema, 60ml volume, 4.0g mesalamine, once daily
DRUGALTH12-1:4
ALTH12-1:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 1.0g N-acetylcysteine
DRUGALTH12-2:4
ALTH12-2:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 2.0g N-acetylcysteine
Sponsors
Altheus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | 6 weeks treatment |
Countries
United States
Outcome results
None listed