Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Prasugrel · 17 trials · 11 indications
The percentage of participants is the total number of participants experiencing a CV death, MI, stroke, UR or GPIIb/IIIa Inhibitor bailout divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee.
ADP-induced PRU represents the rate and extent of ADP-stimulated platelet aggregation and serves as a biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition. Observed PRU values are presented with statistical comparisons of difference in least squares mean (LS mean) PRU values between prasugrel and clopidogrel. Efficacy analyses are analyzed and presented separately for the LD and maintenance dose (MD) phase.
Efficacy analyses are analyzed and presented separately for the loading dose (LD) and MD phase. This primary outcome analysis compares PRU for the 3 prasugrel MDs (10 mg, 7.5 mg, and 5 mg) with the clopidogrel 75-mg MD at 30 days post-MD in the primary cohort (participants who weighed ≥60 kg and were \<75 years). ADP-induced PRU serves as a biomarker of clinical efficacy, with lower values indicating greater P2Y12 platelet inhibition. Observed PRU values are presented with statistical comparisons of LS mean difference between prasugrel and clopidogrel.
The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee.
The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. The data is presented by the study population, which is represented as follows: 1) subjects who presented with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), 2) subjects who presented with ST segment elevation myocardial infarction (STEMI), and 3) all subjects with acute coronary syndromes (ACS) (i.e. all subjects with UA/NSTEMI or STEMI).
AUC of Pras-AM from time 0 up to the last sampling time of 4 hours postdose \[AUC(0-tlast)\] is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and is reported for doses administered on site (0.06, 0.08, and 0.12 mg/kg) during Part B (once-daily repeated dosing phase) of the study. Four participants received the same dose at multiple visits where pharmacokinetic samples were collected.
Accumetrics VN assay: A point-of-care device that measures platelet aggregation. Percentage of platelet inhibition is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and also during the once-daily repeated dosing phase in Part B, at steady state, 14 ± 4 days after each new dose (0.06, 0.08, and 0.12 mg/kg) is administered. One participant received the same dose at multiple visits (Part A) and one participant received the same daily dose during both dosing periods in Part B.
A hemorrhagic event requiring medical intervention. Medical intervention was defined as any medical attention resulting in therapy or further investigation during the 30-day treatment duration.
ADP-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
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.
Maximum platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) was assessed by light transmission aggregometry (LTA).
IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 6 hours after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Measures IPA during maintenance dosing before and after cross-over for each therapy. IPA was defined as (1 - \[maximal platelet aggregation(MPA) at 14 days after study drug treatment\]/\[MPA before drug treatment\]) x 100.
Maximum platelet aggregation (MPA) to 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA).
Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding. A major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. A minor bleed was defined as a clinically overt hemorrhage with a hemoglobin decrease \>=3 g/dL and \<= 5 g/dL.
The AUC of Prasugrel's active metabolite, R-138727, was calculated through the sampling time of the last quantifiable plasma concentration \[AUC(0-tlast)\]. Geometric Least Squares (LS) Means were obtained. The log-transformed AUC was analyzed with a mixed effect model with dose, population, dose\*population interaction as fixed effects, and participant as a random effect.
Cmax was observed from the data and used to calculate Geometric Least Squares (LS) Means. The log-transformed Cmax was analyzed with a mixed effect model with dose, population, dose\*population interaction as fixed effects, and participant as a random effect.
MPA to 20 micromolar (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 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.
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.
AUC from time zero to the last quantifiable plasma concentration (tlast)
AUC from time zero to the last quantifiable plasma concentration (tlast)
| Arm | Type | Description |
|---|---|---|
| Non pre-treatment | EXPERIMENTAL | A placebo oral loading dose is given at the time of diagnosis and a 60 milligrams (mg) oral loading dose of prasugrel is given at the time of PCI followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days. |
| Split Loading Dose | EXPERIMENTAL | A 30 mg oral loading dose of prasugrel is given at diagnosis and a 30 mg oral dose of prasugrel is given at the time of PCI followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days |
| Prasugrel 60/10 Primary | EXPERIMENTAL | Loading dose 60 mg followed by maintenance dose 10 mg/day |
| Prasugrel 30/7.5 Primary | EXPERIMENTAL | Loading dose 30 mg followed by maintenance dose 7.5 mg/day |
| Prasugrel 30/5 Primary | EXPERIMENTAL | Loading dose 30 mg followed by maintenance dose 5 mg/day |
| Clopidogrel 300/75 Primary | ACTIVE_COMPARATOR | Loading dose 300 mg followed by maintenance dose 75 mg/day |
| Prasugrel 30/5 Low Weight/Elderly | EXPERIMENTAL | Loading dose 30 mg followed by maintenance dose 5 mg/day |
| Clopidogrel 300/75 Low Weight/Elderly | ACTIVE_COMPARATOR | Loading dose 300 mg followed by maintenance dose 75 mg/day |
| Prasugrel | EXPERIMENTAL | Prasugrel and Low-dose Commercially-available Aspirin |
| Clopidogrel | ACTIVE_COMPARATOR | Clopidogrel and Low-Dose Commercially-available Aspirin |
| Part A: Prasugrel Single Dose | EXPERIMENTAL | Prasugrel 0.03 milligrams per kilogram (mg/kg) to 0.60 mg/kg dosage to be titrated up or down based on desired platelet inhibition, administered orally \[oral-disintegrating tablet (ODT)\], single dose given up to 3 occasions, at different strengths, with up to 18 days between doses. |
| Part B: Prasugrel Once-Daily Dose | EXPERIMENTAL | Daily prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 30% administered orally, once daily for 10-18 days and then followed by prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 50% administered orally, once daily for 10-18 days, for a total of 20-36 days. |
| 7.5 mg Prasugrel | EXPERIMENTAL | Participants were to receive 7.5 milligrams (mg) of prasugrel orally, once daily if they weighed ≥60 kilograms (kg) and if pharmacodynamic (PD) measures indicated that the 5-mg prasugrel dose did not produce a steady-state PD response equivalent to inhibition of platelet activation (IPA) ≥25%. Because these criteria were not met, no participants received 7.5 mg of prasugrel. |
| Placebo | PLACEBO_COMPARATOR | - |
| 5 mg Prasugrel | EXPERIMENTAL | - |
| Placebo and 60 milligram (mg) Prasugrel | PLACEBO_COMPARATOR | Placebo loading dose administered once orally before percutaneous coronary intervention (PCI) and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. |
| 600 mg Clopidogrel and 60 mg Prasugrel | EXPERIMENTAL | 600-mg clopidogrel loading dose administered once orally before PCI and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. |
| 600 mg Clopidogrel and 30 mg Prasugrel | EXPERIMENTAL | 600-mg clopidogrel loading dose administered once orally before PCI and 30-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. |
| Prasugrel to Clopidogrel | EXPERIMENTAL | One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days. |
| Clopidogrel to Prasugrel | ACTIVE_COMPARATOR | One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days. |
| Prasugrel 10/10 mg | EXPERIMENTAL | Open label (lead-in) dose of clopidogrel 75 milligram (mg) for 10 to 14 days. Upon completion, assignment to a single loading dose of prasugrel 10 mg and placebo, followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. |
| Clopidogrel 75/75 mg | EXPERIMENTAL | Open label (lead-in) dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, assignment to a single loading dose of clopidogrel 75 mg and placebo, followed by maintenance dose of clopidogrel 75 mg taken for 13 to 15 days. |
| Prasugrel 60/10 mg | EXPERIMENTAL | Open label (lead-in) dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, assignment to a single loading dose of prasugrel 60 mg and placebo followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. |
| Prasugrel (CS-747) 40 mg LD/7.5 mg MD | EXPERIMENTAL | Prasugrel (CS-747) 40 mg oral loading dose (LD) at time of percutaneous coronary intervention (PCI) followed by 7.5 mg oral maintenance dose (MD), once daily, for 29-34 days |
| Prasugrel (CS-747) 60 mg LD/10 mg MD | EXPERIMENTAL | Prasugrel (CS-747) 60 mg oral loading dose (LD) at time of PCI followed by 10 mg oral maintenance dose (MD), once daily, for 29-34 days |
| Prasugrel (CS-747) 60 mg LD/15 mg MD | EXPERIMENTAL | Prasugrel (CS-747) 60 mg oral loading dose (LD) at time of PCI followed by 15 mg oral maintenance dose (MD), once daily, for 29-34 days |
| Prasugrel clinical formulation | ACTIVE_COMPARATOR | A single 5-milligram (mg) prasugrel tablet administered orally by swallowing it whole on 1 occasion. |
| Prasugrel (ODT) - on tongue | EXPERIMENTAL | A single 5-mg prasugrel orally disintegrating tablet (ODT) administered orally by placing it on top of the tongue and keeping it there until it disintegrates. |
| Prasugrel (ODT) - apple juice | EXPERIMENTAL | A single 5-mg prasugrel ODT administered orally by placing it on top of the tongue followed by drinking approximately 180 milliliters (ml) apple juice within 1 minute after the tablet finishes disintegration. |
| Prasugrel (ODT) - chewed | EXPERIMENTAL | A single 5-mg prasugrel ODT administered orally by placing it on top of the tongue, but then chewed and swallowed rather than waiting for it to disintegrate. |
| Prasugrel (ODT) - under tongue | EXPERIMENTAL | A single 5-mg prasugrel ODT administered orally by placing it under (rather than on top of) the tongue and keeping it there until it disintegrates. |
| 10 mg prasugrel | ACTIVE_COMPARATOR | - |
| 75 mg clopidogrel | ACTIVE_COMPARATOR | - |
| 5 milligrams (mg) prasugrel | EXPERIMENTAL | - |
| Prasugrel - 60 mg/10 mg | EXPERIMENTAL | Prasugrel 60 mg loading dose given once orally, followed by 10 mg once a day orally for 10 days |
| Prasugrel - 30 mg/7.5 mg | EXPERIMENTAL | Prasugrel 30 mg loading dose given once orally, followed by 7.5 mg once a day orally for 10 days |
| Prasugrel - 30 mg/5 mg | EXPERIMENTAL | Prasugrel 30 mg loading dose given once orally followed by 5 mg once a day orally for 10 days |
| Name | Type | Description |
|---|---|---|
| Placebo | DRUG | Administered once orally |
| Prasugrel | DRUG | Administered orally |
| Clopidogrel | DRUG | Oral, daily, 90 days |
| Commercially-available Aspirin | DRUG | Low-dose aspirin, oral, as prescribed by physician through end of study |
| Placebo for Prasugrel | DRUG | Administered orally |
| Placebo for Clopidogrel | DRUG | Administered orally |
| prasugrel 10 mg | DRUG | 10 mg tablet taken orally |
| prasugrel placebo | DRUG | oral, as blinding mechanism. |
| prasugrel 60 mg | DRUG | 60 mg (six 10-mg tablets) taken orally |
| clopidogrel placebo | DRUG | oral, as blinding mechanism |
| Prasugrel (CS-747) | DRUG | Administered orally |
| Prasugrel (clinical formulation) | DRUG | Administered orally |
| Prasugrel (Orally Disintegrating Tablet [ODT]) | DRUG | Administered orally |
Inclusion Criteria: * Have acute coronary syndrome consisting of non-ST-segment elevation with elevated troponin * Scheduled for coronary angiography/PCI greater than or equal to 2 and less than 24 hours from time of planned randomization, but no more than 48 hours from randomization * Must be elig...
Prasugrel is an investigational small molecule being studied for Acute Coronary Syndromes, Sickle Cell Anemia, Diabetes Mellitus, Cardiovascular Diseases, Healthy Volunteers, and Coronary Arteriosclerosis. It is in Phase 3 clinical development and is not yet approved by the FDA.
Prasugrel is being developed by Eli Lilly and Company, traded on the New York Stock Exchange under the ticker LLY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various cardiovascular and sickle cell disease indications.
Prasugrel is in Phase 3 clinical development. It has completed four trials, including Phase 1 and Phase 2 studies, with a total enrollment of 13,758 participants. The drug remains investigational and has not received FDA approval.
Prasugrel has completed four clinical trials: NCT00059215, a Phase 2 study in patients undergoing percutaneous coronary intervention; NCT01167023, a Phase 2 study in adult sickle cell disease; NCT01430091, a Phase 1 bioavailability study; and NCT01476696, a Phase 2 study in pediatric sickle cell disease.
Yes, Prasugrel is also known as CS-747. The clinical trial NCT00059215, titled 'A Trial of CS-747 (Prasugrel) Compared With Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention,' confirms that CS-747 is an alternative name for Prasugrel.