Darusentan Effect on PET Uptake Heterogeneity

• Status: Completed
• Trial end date: 2011-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to test the hypothesis that myocardial perfusion heterogeneity, quantified by Markovian Homogeneity analysis of cardiac PET perfusion images, will improve in a quantitative manner after treatment with selective ETA receptor antagonist darusentan 100 mg per day for 2 weeks compared to baseline and post-treatment PET scans in clinically stable subjects with coronary atherosclerosis and/or risk factors.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: K.Lance Gould
• Collaborator: Gilead Sciences
• Treatments: Darusentan; LU 135252

Criteria

Inclusion Criteria:

1. Subjects must be competent to provide written informed consent. Subjects must sign an IRB approved ICF and HIPAA Authorization prior to the initiation of any study procedures. All men must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking study drug, and queried regarding their understanding of the potential risks as described in the ICF.

2. Subjects must be greater than 18 years of age.

3. Female subjects must be surgically sterile or documented as post-menopausal for at least 2 years.

4. Subjects must have documented coronary artery disease as evidenced by previous myocardial infarction, interventional procedure, significant stenosis by cardiac catheterization, or an abnormal perfusion study.

5. Subjects must have an abnormal PET scan.

Exclusion Criteria:

1. Subjects with acute heart failure

2. Subjects with sustained or symptomatic hypotension (SBP 90 mmHg)

3. Subjects with uncontrolled hypertension (SBP of 170 mmHg or DBP of 100 mmHg) at Screening

4. Subjects with unstable angina pectoris

5. Subjects with acute myocardial infarction, stroke, transient ischemic attack, or coronary angioplasty within the last 6 months

6. Subjects with primary valvular disease

7. Subjects with significant vascular aneurysm

8. Subjects with a documented history of renal failure

9. Subjects with liver disease (total bilirubin 3 mg/dL or serum ALT or AST >2X ULN)

10. Subjects with active malignancy

11. Subjects with a fatal non-cardiovascular disease that they are expected to succumb to within 1 year

12. Female subjects that are pregnant or lactating

13. Female subjects with the potential for child-bearing

14. Female subjects being treated with hormone therapies

15. Subjects with uncontrolled diabetes mellitus

16. Subjects with diabetes with gastro paresis or severe neuropathy

17. Subjects with a history of substance abuse within the last 2 years

18. Subjects who have participated in a clinical study involving another investigational drug or device within 1 month of the Screening Visit

19. Subjects with known hypersensitivity or allergy to L-arginine, aminophylline, adenosine, or dipyridamole

20. Subjects who have a planned surgical procedure during the course of the study

21. Subjects taking herbal food supplements (L-carnitine, L-arginine or Ginko biloba)

22. Subjects with known active or dormant type 2 herpes simplex virus infections

23. Subjects with a contraindication to treatment with an ERA. Contraindications may include, but are not limited to, evidence of elevated liver function tests (e.g., aminotransferases >2X ULN) or an event defined as a serious adverse event attributed to previous treatment with an ERA

24. Subjects who are judged by the investigator to be ineligible for this study for any other reason