Safety, Pharmacokinetics and Potential Activity of HE3286 in Obese Adult Subjects

A Phase I, Double-Blind, Placebo-Controlled, Dose Ranging Study of the Safety, Tolerance, Pharmacokinetics and Potential Activity of HE3286 When Administered Orally to Obese Adult Subjects for 28 Days

The objectives of this study are to evaluate the safety, tolerance and pharmacokinetics of HE3286 when administered daily for 28 days to obese adult subjects and to assess potential activity of HE3286 to decrease insulin resistance. An open-label cohort of 6 patients with type II diabetes mellitus will be treated at 10 mg (5 mg BID).

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: HE3286

Detailed Description

HE3286 has a potentially new mechanism of action that may improve the current therapeutic options available to patients with metabolic disorders, inflammatory and autoimmune diseases. In preclinical experiments, HE3286 has shown to have anti-inflammatory activity associated with corticosteroids but without the side effects known with corticosteroid use, such as immune suppression and bone loss. HE3286 has demonstrated glucose-lowering and insulin-enhancing effects in several preclinical mouse and rat models of insulin resistance. In these experiments, HE3286 lowered blood glucose levels and prevented progression of hyperglycemia and HE3286 appeared to enhance insulin sensitivity.

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
  • Texas
    • San Antonio, Texas, United States, 78229
      • Dgd Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Males or females between 18 and 65 years of age
• Body mass index for females between 29 and 35 kg/m2 and no more than 37 kgm2 for males
• Fasting blood glucose level < 126 mg/dL at screening
• 2 hour postprandial (following 75 grams glucose) blood glucose between 140 to 200 mg/dL
• Normal thyroid stimulating hormone with or without thyroid replacement therapy
• Fasting triglycerides < 350 mg/dL
• For females of reproductive potential, agree to avoid pregnancy during the study and for 3 months following study completion, have a negative serum and/or urine pregnancy test, and use an acceptable method of birth control
• Non-smoker or has not smoked for 6 months prior to the screening visit
• No history of alcohol abuse within 2 years
• Negative drug screen at screening and baseline
• Stable weight (+/- 5%); no history of weight loss or gain (> 10% body weight)
• Must provide voluntary, written, informed consent prior to screening evaluations
• Must be able to swallow capsules

Main Exclusion Criteria:

• Marked prolongation of QT/QTc interval or history of additional risk factors for Torsades de Pointes at screening or baseline
• Positive for HIV, HAV, HBV or HCV
• History of clinically significant cardiovascular, hepatic, respiratory or renal or endocrine disorders
• History of breast and/or prostate cancer
• Clinically significant neurological or psychiatric condition, uncontrolled hypertension, clinically significant unstable medical abnormality, chronic disease or active, serious clinical infection or condition
• Personal or family member with breast and/or prostate cancer
• Malignancy within past 5 years except for successfully treated basal cell carcinoma of the skin
• Personal and/or family history of venous thromboembolism
• History of stroke and/or heart attack
• Medication prohibited from study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

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
To assess the potential activity of HE3286 to decrease insulin resistance	duration of study

Collaborators and Investigators

• Sponsor: Harbor Therapeutics
• Investigators: Study Director: Dwight R. Stickney, MD, Harbor Therapeutics

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (Estimate): November 8, 2007

Study Record Updates

• Last Update Posted (Estimate): May 13, 2010
• Last Update Submitted That Met QC Criteria: May 11, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; insulin resistance; phase I; tolerance; obese
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: HE3286-0102