Evaluation of ALT-2074 in Subjects With Type-2 Diabetes, Haptoglobin Type 2-2 Genotype and Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of ALT 2074 in Subjects With Type 2 Diabetes Who Have a Haptoglobin Type 2-2 Genotype and Coronary Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00491543
• Other study ID #: ALT-2074-201
• Status: Completed
• Phase: Phase 2
• First received: June 23, 2007
• Last updated: July 1, 2008
• Start date: June 2007
• Est. completion date: May 2008

Study information

• Verified date: June 2007
• Source: Synvista Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

ALT-2074 (BXT-51072) belongs to a class of drugs called "glutathione peroxidase mimics." ALT-2074 works by imitating a substance produced in various tissues in the body, which prevents damage of the heart and blood vessels. Diabetic patients with a haptoglobin 2-2 genotype have poor cardiovascular clinical outcomes.

The purpose of this study is to assess the safety, the pharmacokinetic profile and characterize the effect on biomarkers of inflammation and oxidative stress of repeat doses of ALT 2074. Subjects must be diabetic, with evidence of coronary artery disease and a haptoglobin 2-2 genotype

Description:

Subjects will be male and female, 18 to 75 years old, with Type 2 diabetes mellitus, a documented or suspected history of coronary artery disease, and a Haptoglobin type 2-2 (Hp 2-2) genotype. Subjects on prescribed anti-diabetic and coronary artery disease medications may continue to take their medications throughout the study.

Subjects who qualify will receive active drug (ALT-2074 20 mg, 40 mg or 80 mg) or placebo every 8 hours for 28 days. There will be three sequential cohorts of increasing doses of active drug. There will be 2 follow-up visits (Days 35 and 42). Blood and urine tests for safety (chemistry and hematology), pharmacokinetics and relevant biomarkers to measure inflammation and oxidative stress will be performed throughout the study. Electrocardiograms and 24-hour Holter monitoring will also be performed at various time points during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

1. Male or female, 18 to 75 years of age.

2. Diagnosis of Type 2 diabetes mellitus

3. Stable coronary artery disease (CAD) documented or suspected, not requiring adjustment for =2 months, as determined by: a. A history of myocardial infarction verified by Q-wave electrocardiogram and/or medical records, occurring greater than 6 months before the screening Visit; OR b. A coronary angiogram and/or stress test; OR c. A ankle brachial pressure index less than 0.9; OR d. Age greater than 60 years of age

4. Hp 2-2 genotype.

5. Ability to communicate and comply with all study requirements.

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes
• Myocardial Ischemia

Intervention

Drug:
• ALT-2074

Locations

Country	Name	City	State
United States	Radiant Research	Chicago	Illinois
United States	Radiant Research	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Synvista Therapeutics, Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

Blum S, Asaf R, Guetta J, Miller-Lotan R, Asleh R, Kremer R, Levy NS, Berger FG, Aronson D, Fu X, Zhang R, Hazen SL, Levy AP. Haptoglobin genotype determines myocardial infarct size in diabetic mice. J Am Coll Cardiol. 2007 Jan 2;49(1):82-7. Epub 2006 Dec 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers of inflammation and oxidative stress		28 days
Primary	Safety		28 days
Primary	Pharmacokinetics		28 days