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20090417 A Prospective Randomized Trial of CMX- 2043, a Lipoic Acid-Based Cytoprotectant, In Patients Undergoing Elective PCI: Primary Results of the SUPPORT-1.

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Presentation on theme: "20090417 A Prospective Randomized Trial of CMX- 2043, a Lipoic Acid-Based Cytoprotectant, In Patients Undergoing Elective PCI: Primary Results of the SUPPORT-1."— Presentation transcript:

1 A Prospective Randomized Trial of CMX- 2043, a Lipoic Acid-Based Cytoprotectant, In Patients Undergoing Elective PCI: Primary Results of the SUPPORT-1 Trial Mitchell W. Krucoff, C.K. Ponde, Jagdish Hiremath, Mullasari Ajit, Eddison Ramsaran, Manesh R. Patel, Alan S. Lader, F. Howard Schneider, Reinier Beeuwkes, C. Michael Gibson, and James E. Tcheng.

2 Conflict of Interest   Clinical Advisory Board, Ischemix

3 Incidence & Implications of Peri-Procedural MI: A Controversy of Definitions & Pathophysiology  Resolute All Comers  2,121 patients Incidence: % 3 yr mortality: 2-8%

4 PCI: A Human Laboratory for Cytoprotection  PCI produces enzymatic events  Selected protein elevations (CPK-MB, Troponin) represent myocellular necrosis  PCI as a laboratory for RCT of cytoprotective strategies has FDA predicate (vitamin B6 metabolite  PCI as a laboratory for RCT of cytoprotective strategies has FDA predicate (vitamin B6 metabolite pyridoxal-5’- phosphate monohydrate (MC- 1) in the MC-1 to Eliminate Necrosis and Damage (MEND-1)

5 CMS-2043: A Novel Molecular Entity to Inhibit Ischemic Apoptosis Reactive oxygen species (ROS) anti-oxidant, AND Activates Akt (Ak mouse thymoma = Protein kinase B) via tyrosine kinase (TK)

6 The SUPPORT 1 Study Safety and Efficacy of CMX-2043 in Subjects Undergoing PCI and Peri- Operative Reperfusion Treatment

7 SUPPORT-1: Study Design   Phase IIa Safety & Efficacy: CMX-2043   Prospective, randomized 3:1 3 doses (0.8, 1.6 & 2.4 mg/kg) vs placebo   Multi-center (N=6)   Elective PCI Patients WNL biomarkers & Non-acute ECG Receiving single stent of ≥ 18 mm or multiple stents   Primary Outcome Measures: Incidence of CK-MB elevation <24 hours following PCI Change in cardiac biomarkers <24 hrs following PCI   CK-MB, Troponin T   Secondary Outcome Measure: MI as >X3 peak CPK

8 SUPPORT-1 Exclusion Criteria   Acute/unstable angina   MI within 14 days   Coagulopathy   Clinical valvular disease   Clinical peripheral vascular disease   TIA, stroke or IC bleed within 90 days   Creatinine level ≥ 1.5 times ULN

9 SUPPORT-1 Sites and Investigators

10 SUPPORT I: Patient Accrual/Randomization

11 SUPPORT-1 Baseline Characteristics

12 SUPPORT I: Arteries Stented Per Rx Group

13 Primary Endpoint: 24 Hr CK-MB Change from Baseline

14 Hr CK-MB Change From Baseline (ng/mL) CMX-2043 treatment p=0.05 vs. Placebo p = 0.05

15 Hr Troponin T Change from Baseline CMX-2043 treatment

16 Hr Peri-Procedural MI by CK-MB >X3 ULN CMX-2043 treatment p=0.024 vs. Placebo

17 Hr Peri-Procedural MI by Troponin T >X3 ULN CMX-2043 treatment p=0.050 vs. Placebo

18 SUPPORT-1 Adverse Events Summary Category 0.8 mg/kg (N = 36) 1.6 mg/kg (N = 35) 2.4 mg/kg (N = 36) Placebo (N = 34) Any AEs7 ( 19.44%)14 ( 40.00%)11 ( 30.56%)10 ( 29.41%) Drug Related AEs0 ( 0.00%)3 ( 8.57%)1 ( 2.78%)2 ( 5.88%) Serious AEs1 ( 2.78%)2 ( 5.71%)1 ( 2.78%)0 ( 0.00%) AEs leading to Study discontinuation 0 ( 0.00%)1 ( 2.86%)0 ( 0.00%) Deaths0 ( 0.00%)

19 SUPPORT I: Limitations  Serum marker elevations with elective PCI have biochemical relevance for NME testing vs. human apoptosis, however the clinical relevance of these findings is unproven

20 SUPPORT I Primary Results: Conclusions  SUPPORT I was a prospective, randomized, multicenter Phase IIa dosing study of protection from PCI-induced myonecrosis by CMX-2043 infusion  All doses of CMX-2043 studied (0.8, 1.6 and 2.4 mg/kg) appeared safe in this population  High dose (2.4 mg/kg) infusion of CMX-2043 was associated with statistically significant reduction of serum markers of myonecrosis and MI defined by >3X elevation above ULN  Results of SUPPORT I suggest the basis for further study and a Phase III study design


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