Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3)

Coronary Artery Disease Clinical Trial

— OPTIMUS-3  

Official title:

A Pharmacodynamic Comparison of Prasugrel (LY640315) Versus High Dose Clopidogrel in Subjects With Type 2 Diabetes Mellitus and Coronary Artery Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00642174
• Other study ID #: 11241
• Secondary ID: H7T-MC-TACA
• Status: Completed
• Phase: Phase 2
• First received: March 21, 2008
• Last updated: February 19, 2010
• Start date: April 2008
• Est. completion date: January 2009

Study information

• Verified date: February 2010
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This trial is designed as a phase 2 randomized, double-blind double dummy, active comparator controlled, two-period two-arm crossover study to enroll 40 patients across multiple centers. The study will compare platelet function following a prasugrel loading dose and 1 week of prasugrel maintenance therapy with high-dose clopidogrel loading dose and 1 week of high-dose clopidogrel maintenance therapy in patients with drug treated type 2 diabetes mellitus who have coronary artery disease. Various assays of platelet function will be used in this study. Platelet function will be studied using the following assays: Accumetrics VerifyNowTM P2Y12, Light Transmittance Aggregometry (LTA), Vasodilator-associated stimulated phosphoprotein (VASP), and Thromboelastography (TEG)-platelet mapping.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Type 2 Diabetes Mellitus and on oral or parenteral hypoglycemic therapy for at least 1 month.

• History of Coronary Artery Disease with or without other types of vascular disease (such as peripheral vascular disease).

• Taking Aspirin 75-325 mg/day for at least 1 week prior to randomization.

• Between the ages of 18-74 years old.

• If a woman of child bearing age, must not be pregnant and must agree to use reliable method of birth control during the duration of the study.

Exclusion Criteria:

• Thienopyridine therapy within 30 days or have a defined need for thienopyridine treatment.

• Coronary Artery Bypass Graft (CABG) or Percutaneous Coronary Intervention (PCI) with no stent placed within 30 days.

• Planned coronary revascularization

• Hemoglobin A1c (HbA1c) > or equal to 10 mg/dL within the last 3 months.

• Received fibrolytic therapy <24 hours prior to randomization.

• Received non-fibrin-specific fibrinolytic therapy <48 hours prior to randomization.

• At risk of bleeding.

• History of ischemic stroke, transient ischemic attack (TIA), intercranial neoplasm, arteriovenous malformation, or aneurysm.

• Body weight <60 kilograms (kg).

• International Normalized Ratio (INR) >1.5, platelet count <100,000/mm3, or anemia (hemoglobin <10 gm/dL) within 1 week of study entry.

• Are receiving or will receive oral anticoagulation or antiplatelet treatment therapy.

• Are being treated with daily non-steroidal anti-inflammatory drugs (NSAIDS).

• Are pregnant, breast-feeding or plan to become pregnant.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• prasugrel
Oral prasugrel 60-mg loading dose, followed by 6-9 days of oral prasugrel 10-mg/day tablet maintenance dose.
• Clopidogrel
Oral clopidogrel 600-mg loading dose, followed by 6-9 days of oral clopidogrel 150-mg/day tablet maintenance dose.

Locations

Country	Name	City	State
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Jacksonville	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oklahoma City	Oklahoma
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay	The inhibition of platelet aggregation 4 hours after the loading dose was administered was assessed using the Accumetrics VerifyNow™ P2Y12 assay. Percentage inhibition, as reported by VerifyNow™ P2Y12, was calculated from P2Y12 Reaction Unit (PRU) (rate and extent of adenosine diphosphate [ADP]-stimulated platelet aggregation) and BASE (estimate of baseline platelet reactivity independent of P2Y12 receptor inhibition [reference values]: rate and extent of Thrombin Receptor-Activated Peptide-stimulated platelet aggregation) values as follows: Percentage (%) inhibition = (1-PRU/BASE) x 100.	4 hours after loading dose	Yes
Secondary	Inhibition of Platelet Aggregation at 1- and 24-Hours After Loading Dose (LD) and 24-Hours After Last Maintenance Dose (LMD) Assessed by Accumetrics VerifyNow™ P2Y12 Assay	Inhibition of platelet aggregation 1- and 24-hours after loading dose and 24-hours after last maintenance dose was administered was assessed using Accumetrics VerifyNow™ P2Y12 assay. Percentage inhibition, as reported by VerifyNow™ P2Y12, was calculated from PRU (rate and extent of ADP-stimulated platelet aggregation) and BASE (estimate of baseline platelet reactivity independent of P2Y12 receptor inhibition [reference values]: rate and extent of Thrombin Receptor-Activated Peptide-stimulated platelet aggregation) values as follows: Percentage (%) inhibition = (1-PRU/BASE) x 100.	1 hour and 24 hours after the loading dose (LD) and 24 hours after the last maintenance dose (LMD)	Yes
Secondary	Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)	Mean platelet aggregation (MPA) to 5 and 20 µM adenosine diphosphate (ADP) was assessed by light transmittance aggregometry (LTA). Platelet aggregation was monitored for a total of 7 minutes after addition of ADP. Maximum platelet aggregation was the maximal aggregation value achieved during the 7-minute observation period following addition of agonists.	Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose	Yes
Secondary	Platelet Reactivity Index (PRI)	Data from the Vasodilator-associated stimulated phosphoprotein assay were reported as the platelet reactivity index (PRI) which was calculated from corrected mean fluorescence intensity (cMFI) following incubation of platelets with either prostaglandin E1 (PGE1) alone or PGE1 plus ADP: Platelet Reactivity Index (%) = [1-(cMFI PGEI+ADP/cMFI PGEI)] x 100. Lower PRI values indicate greater platelet P2Y12 inhibition.	Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose	Yes
Secondary	Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate	Thromboelastography (TEG) platelet mapping (MP) maximum amplitude (MA) - Adenosine Diphosphate (ADP) millimeters (mm) at each time point. The TEG-MP MA measures strength of clot formation in whole blood. MA-ADP is the maximal amplitude resulting from fibrin and platelets not blocked by ADP-receptor inhibiting drugs. Fibrin strands in blood sample link a rotating sample cup with a stationary pin suspended by a torsion wire. The degree of platelet contribution to the MA through platelet-fibrin bonding directly influences the magnitude of pin movement and ultimately the amplitude of the tracing.	Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose	Yes

External Links

•   Lilly Clinical Trial Registry