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

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: mesalamine; Drug: ALTH12-1:4; Drug: ALTH12-2:4

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Foundation for Digestive Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Comparator; Mesalamine enema	Drug: mesalamine; 4.0g mesalamine rectal suspension, rectally administered enema, 60ml volume, 4.0g mesalamine, once daily; Other Names: Rowasa; 5-ASA; 5-aminosalicylic acid
Experimental: ALTH12-1:4; ALTH12-1:4 experimental treatment dose	Drug: ALTH12-1:4; ALTH12-1:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 1.0g N-acetylcysteine; Other Names: NAC; 5-ASA; mesalamine; N-acetylcysteine; enema
Experimental: ALTH12-2:4; ALTH12-2:4 experimental treatment dose	Drug: ALTH12-2:4; ALTH12-2:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 2.0g N-acetylcysteine; Other Names: NAC; 5-ASA; mesalamine; N-acetylcysteine

What is the study measuring?

Primary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Altheus Therapeutics, Inc.
• Investigators: Principal Investigator: Philip B Miner, M.D., Oklahoma Foundation for Digestive Research

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: November 20, 2009
• First Submitted That Met QC Criteria: November 23, 2009
• First Posted (Estimate): November 24, 2009

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 28, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: ulcerative colitis; inflammatory bowel disease; colitis; rectal administration; enema; mesalamine
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Protective Agents; Anti-Bacterial Agents; Respiratory System Agents; Antioxidants; Antidotes; Antitubercular Agents; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine; Mesalamine; Aminosalicylic Acid
• Other Study ID Numbers: ALTH12-003