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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Placebo
* Drug: HE3286


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Experimental: 2<br>HE3286 5 mg daily | Drug: HE3286<br>* daily for 28 days<br>* Other names: Triolex;|
| Experimental: 3<br>HE3286 10 mg daily | Drug: HE3286<br>* daily for 28 days<br>* Other names: Triolex;|
| Experimental: 4<br>HE3286 20 mg daily | Drug: HE3286<br>* daily for 28 days<br>* Other names: Triolex;|
| Experimental: 5<br>HE3286 4 mg daily | Drug: HE3286<br>* daily for 28 days<br>* Other names: Triolex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and pharmacokinetics |  | duration of the study | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phase I/II, ulcerative colitis, safety, tolerance, pharmacokinetics