Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease (GENERATIONS)
This study has been completed.
Sponsor:
Eli Lilly and Company
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
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Coronary Artery Disease |
Drug: prasugrel Drug: clopidogrel |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel and Clopidogrel in Very Elderly Versus Non-Elderly Aspirin-Treated Subjects With Stable Coronary Artery Disease |
Resource links provided by NLM:
MedlinePlus related topics:
Coronary Artery Disease
Drug Information available for:
Clopidogrel bisulfate
U.S. FDA Resources
Further study details as provided by Eli Lilly and Company:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
| Enrollment: | 155 |
| Study Start Date: | March 2010 |
| Study Completion Date: | October 2011 |
| Primary Completion Date: | October 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 5 milligrams (mg) prasugrel |
Drug: prasugrel
administered orally, daily for 12 days
Other Names:
|
| Active Comparator: 10 mg prasugrel |
Drug: prasugrel
administered orally, daily for 12 days
Other Names:
|
| Active Comparator: 75 mg clopidogrel |
Drug: clopidogrel
Administered orally, daily for 12 days
|
Eligibility| Ages Eligible for Study: | 45 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01107912
Locations
| United States, Florida | |
| 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, 32209 | |
| United States, Maryland | |
| 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. | |
| Baltimore, Maryland, United States, 21215 | |
| United States, Ohio | |
| 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. | |
| Cincinnati, Ohio, United States, 45212 | |
| Ireland | |
| 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. | |
| Dublin, Ireland, 9 | |
| Netherlands | |
| 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. | |
| Nieuwegein, Netherlands, 3435 CM | |
| Sweden | |
| 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. | |
| Lund, Sweden, 22185 | |
| 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. | |
| Malmo, Sweden, 20502 | |
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
Investigators
| 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 |
More Information
No publications provided
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT01107912 History of Changes |
| Other Study ID Numbers: | 12835, H7T-MC-TACY |
| Study First Received: | April 19, 2010 |
| Results First Received: | September 27, 2012 |
| Last Updated: | September 27, 2012 |
| Health Authority: | United States: Food and Drug Administration Sweden: Medical Products Agency Ireland: Irish Medicines Board Netherlands: Medicines Evaluation Board (MEB) |
Keywords provided by Eli Lilly and Company:
|
Platelet function |
Additional relevant MeSH terms:
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Clopidogrel Prasugrel Platelet Aggregation Inhibitors |
Hematologic Agents Therapeutic Uses Pharmacologic Actions Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 19, 2013