Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease (GENERATIONS)

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01107912
First received: April 19, 2010
Last updated: September 27, 2012
Last verified: September 2012

April 19, 2010
September 27, 2012
March 2010
October 2011   (final data collection date for primary outcome measure)
Change in Maximum Platelet Aggregation (MPA) to 20 Micromoles (μM) Adenosine Diphosphate (ADP) as Measured by Light Transmission Aggregometry (LTA) From Baseline to 12 Days of Therapy in the First Treatment Period [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). Lower MPA values reflect stronger platelet inhibition, whereas higher MPA values reflect weaker inhibition.
Change in maximum platelet aggregation (MPA) to 20 uM adenosine diphosphate (ADP) as measured by light transmission aggregometry (LTA) from baseline to 12 days of therapy in the first treatment period [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01107912 on ClinicalTrials.gov Archive Site
  • Change in Vasodilator-associated Stimulated Phosphoprotein (VASP) From Baseline to 12 Days of Therapy [ Time Frame: Baseline, Day 12 ] [ Designated as safety issue: No ]
    Vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12, whereas a higher PRI reflects weaker inhibition of P2Y12.
  • Change in VerifyNow P2Y12 Reaction Units (PRU) From Baseline to 12 Days of Therapy [ Time Frame: Baseline, Day 12 ] [ Designated as safety issue: No ]
    The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in P2Y12 reaction units (PRU). PRU report the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of the rate and extent of platelet aggregation in the presence of adenosine phosphate ADP. A lower PRU reflects stronger inhibition of P2Y12, whereas a higher PRU reflects weaker inhibition of P2Y12.
  • Active Metabolite Blood Levels to Drug Exposure as Measured by Pharmacokinetics (PK) Through 4 Hours After Dosing [ Time Frame: Baseline up to 4 hours post-dose ] [ Designated as safety issue: No ]
    A descriptive pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing prasugrel and clopidogrel active metabolite exposures to MPA in response to 20 µM ADP (by LTA) was conducted as originally intended; however, the graphic output from that analysis is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours [AUC (0-4)] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances.
  • Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) From Baseline at Day 12 of Therapy [ Time Frame: Baseline, Day 12 ] [ Designated as safety issue: No ]
    Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing the platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.
  • Change in vasodilator-associated stimulated phosphoprotein (VASP) from baseline to 12 days of therapy [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
  • Change in VerifyNow P2Y12 reaction units (PRU) from baseline to 12 days of therapy [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
  • Change in MPA associated with exposure to drug active metabolite blood levels as measured by pharmacokinetics from baseline to 12 days of therapy [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
  • Change in maximum platelet aggregation (MPA)as measured by light transmission aggregometry (LTA) from baseline to 12 days of therapy [ Time Frame: Baseline, 12 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease
A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel and Clopidogrel in Very Elderly Versus Non-Elderly Aspirin-Treated Subjects With Stable Coronary Artery Disease

The 5-milligram (mg) maintenance dose (MD) of prasugrel in very elderly patients with coronary artery disease produces a pharmacodynamic response within the same therapeutic range as 10-mg MD in non-elderly patients.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Coronary Artery Disease
  • Drug: prasugrel
    administered orally, daily for 12 days
    Other Names:
    • Efient
    • Effient
    • LY640315
    • CS747
  • Drug: clopidogrel
    Administered orally, daily for 12 days
  • Experimental: 5 milligrams (mg) prasugrel
    Intervention: Drug: prasugrel
  • Active Comparator: 10 mg prasugrel
    Intervention: Drug: prasugrel
  • Active Comparator: 75 mg clopidogrel
    Intervention: Drug: clopidogrel
Erlinge D, Gurbel PA, James S, Lindahl TL, Svensson P, Ten Berg JM, Foley DP, Wagner H, Brown PB, Luo J, Zhou C, Moser BA, Jakubowski JA, Small DS, Winters KJ, Angiolillo DJ. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol. 2013 Aug 13;62(7):577-83. doi: 10.1016/j.jacc.2013.05.023. Epub 2013 Jun 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
155
October 2011
October 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants (Either: at least 45 years of age, but less than 65 years of age OR 75 years of age or older) with a history of stable coronary artery disease who are not currently indicated for treatment with a thienopyridine (that is, prasugrel, clopidogrel, or ticlopidine)
  • Provision of written informed consent
  • Body weight greater than or equal to 60 kilograms (kg)
  • For women of child-bearing potential only (that is, women who are not surgically or chemically sterilised and who are between menarche and 1 year post menopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomisation) and agree to use a reliable method of birth control during the study

Exclusion Criteria:

  • Unstable coronary artery disease
  • Myocardial Infarction (MI) within the previous 30 days
  • Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft Surgery (CABG) within the previous 90 days
  • History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 3 months prior to enrollment
  • Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation
  • Any known contraindication to treatment with an antiplatelet agent
  • Significant hypertension at the time of screening or randomisation
  • Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator's opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator
  • Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders
  • Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, Transient Ischemic Attack (TIA) or stroke
  • Prior history of thrombocytopenia or thrombocytosis
  • Use of antiplatelet agents (besides aspirin) within 10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or participants receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study
Both
45 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Ireland,   Netherlands,   Sweden
 
NCT01107912
12835, H7T-MC-TACY
No
Eli Lilly and Company
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP