Safety and Pharmacokinetics Study of HE3286 in Patients With Active, Mild-to-Moderate Ulcerative Colitis

A Phase I/II, Double-Blind, Randomized, Placebo-Controlled, Dose Ranging Study of the Safety, Tolerance, Pharmacokinetics and Activity of HE3286 When Administered Orally to Patients With Active, Mild-to-Moderate Ulcerative Colitis

The purpose of this pilot, exploratory study is to evaluate the safety, tolerance, pharmacokinetics and potential activity of an investigational agent, HE3286, when administered orally, daily for 28 days to patients with mild-to-moderate ulcerative colitis.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: HE3286

Detailed Description

HE3286 has a potentially new mechanism of action that may improve the current therapeutic options available to patients with ulcerative colitis. In preclinical experiments, HE3286 has shown activity in animal models of ulcerative colitis. Additionally, HE3286 has shown to have anti-inflammatory activity associated with corticosteroids but without the side effects associated with corticosteroid use, such as immune suppression and bone loss.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
  • California
    • Anaheim, California, United States, 92801
    • Fresno, California, United States, 93726
    • La Jolla, California, United States, 92037
  • Colorado
    • Denver, Colorado, United States, 80205
    • Denver, Colorado, United States, 80215
  • Florida
    • Winter Park, Florida, United States, 32789
  • Georgia
    • Atlanta, Georgia, United States, 30342
  • Kentucky
    • Louisville, Kentucky, United States, 40536
  • Texas
    • El Paso, Texas, United States, 79905

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years of age
• Diagnosed (> 6 weeks) or recently relapsed active mild-to-moderate ulcerative colitis based on colonoscopy or flexible sigmoidoscopy
• Mayo Scoring System for Assessment of Ulcerative Colitis Activity score of 4-9
• Stable dose prior to screening of 6-mercaptopurine (50-150 mg/day 6-MP) [at least 2 months], Azathioprine (50-100 mg/day) [at least 2 months], and 5-ASA [at least 2 weeks]
• For females of reproductive potential, agree to avoid pregnancy during the study and for 3 months following study completion, have a negative serum pregnancy test (b-HCG) at screening and negative urine pregnancy test and use an acceptable method of birth control
• No history of narcotic and/or alcohol abuse within 2 years of screening and agrees to consume < 6 oz. of wine or equivalent per day
• No experienced renal or liver disease by history and/or based on laboratory results
• Must provide voluntary, written, informed consent prior to screening evaluations and be able to follow verbal and written instructions
• Must be able to swallow capsules

Exclusion Criteria:

• Primary sclerosing cholangitis
• Positive for C. difficile toxin in the stool
• Requires hospitalization for treatment of severe ulcerative colitis
• History of clinically significant cardiovascular disease (including coronary artery disease), clinically significant hepatic, respiratory or renal abnormalities, or clinically significant endocrine disorders (not including diabetes)
• Clinically significant abnormalities on laboratory results (renal insufficiency, liver function abnormalities, abnormal WBC or ANC)
• Any clinically significant unstable medical abnormality, chronic disease, or active, serious clinical infection or condition, other than ulcerative colitis
• Uncontrolled hypertension defined as systolic BP > 160 mmHg and/or diastolic BP > 100 mmHg on three or more assessment on more than one day(blood pressure must be stable for > 3 months prior to screening)
• Malignancy within the past 5 years, except for successfully treated basal cell carcinoma of the skin
• Requiring or receiving anti-TNF-a or other immune modulating drugs (other than 6-MP or azathioprine) within 8 weeks prior to screening
• Requiring or receiving any of the following within 4 weeks of the screening visit: interleukins, steroids (i.e., anabolic steroids, glucocorticoids), narcotics, anti-cancer chemotherapeutic agents, metabolic inhibitors or nutraceuticals with immune enhancement claims
• Requiring oral or intravenous cortisone
• Requiring corticosteroid enemas
• Acute illness within 10 days prior to Day 1 or taking antibiotics for UC (but not for a infectious disease) within 14 days of Day 1
• Any clinical condition or receiving therapy that, in the opinion of the Investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 1; Placebo	Drug: Placebo; Placebo
EXPERIMENTAL: 2; HE3286 5 mg daily	Drug: HE3286; daily for 28 days; Other Names: Triolex
EXPERIMENTAL: 3; HE3286 10 mg daily	Drug: HE3286; daily for 28 days; Other Names: Triolex
EXPERIMENTAL: 4; HE3286 20 mg daily	Drug: HE3286; daily for 28 days; Other Names: Triolex
EXPERIMENTAL: 5; HE3286 4 mg daily	Drug: HE3286; daily for 28 days; Other Names: Triolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety and pharmacokinetics	duration of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
assess activity on the signs and symptoms of active mild-to-moderate ulcerative colitis	duration of the study

Collaborators and Investigators

• Sponsor: Harbor Therapeutics
• Investigators: Principal Investigator: Dwight R Stickney, MD, Harbor Therapeutics

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): May 1, 2009

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (ESTIMATE): March 5, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 14, 2011
• Last Update Submitted That Met QC Criteria: June 11, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; ulcerative colitis; tolerance; phase I/II
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: HE3286-0301