Study of the Safety and Tolerability of ALTH12 Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020708
• Other study ID #: ALTH12-003
• Status: Completed
• Phase: Phase 1
• First received: November 20, 2009
• Last updated: March 28, 2011
• Start date: November 2009
• Est. completion date: September 2010

Study information

• Verified date: March 2011
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• 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 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.

Study Design

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• mesalamine
4.0g mesalamine rectal suspension, rectally administered enema, 60ml volume, 4.0g mesalamine, once daily
• ALTH12-1:4
ALTH12-1:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 1.0g N-acetylcysteine
• ALTH12-2:4
ALTH12-2:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 2.0g N-acetylcysteine

Locations

Country	Name	City	State
United States	Oklahoma Foundation for Digestive Research	Oklahoma City	Oklahoma

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	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	Yes