sickle cell disease
Conditions
Interventions
Product Name: prasugrel
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: PRASUGREL
CAS Number: 150322-43-3
Concentration unit: mg milligram(s)
Concentration type: range
Concentration nu
Sponsors
Eli Lilly and Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Are male or female with SCD [(homozygous sickle cell (HbSS) and hemoglobin S beta ^0 thalassemia (HbS ß^0 thalassemia)] •Have a body weight =12 kilograms (kg) and are =2 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Known to have hemoglobin C sickle cell (HbSC) or hemoglobin S beta ^plus thalassemia (HbS ß^+ thalassemia) genotypes •Vaso-occlusive crisis (VOC) requiring medical attention within 15 days prior to screening •Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival •Hepatic dysfunction characterized by alanine aminotransferase (ALT) = 3 times the upper limit of normal (ULN) •Renal dysfunction requiring chronic dialysis or creatinine = 1.5 milligrams per deciliter (mg/dL) •Contraindication for antiplatelet therapy •History of intolerance or allergy to approved thienopyridines (clopidogrel, ticlopidine, or prasugrel) •Participants with a hematocrit 300 red blood cells (RBC)/high-powered field (HPF) on urinalysis at the time of screening •Any history of vitreous hemorrhage •Prior history of hemorrhagic or ischemic stroke, a transient ischemic attack (TIA), or other intracranial hemorrhage •Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding •Platelet count <100,000 per microliter (µl) of blood •Have had recent surgery (within 30 days prior to screening) or are scheduled to undergo surgery within the next 60 days •History of dysfunctional uteral bleeding, in the judgment of the investigator •Treatment with packed RBC or whole blood transfusion therapy within 30 days prior to dosing •Any nonsteroidal anti-inflammatory drug (NSAID) use within 5 days prior to screening •Any aspirin, warfarin, thienopyridine, or other antiplatelet medication use within 10 days prior to dosing •Anticipated use of aspirin, warfarin, thienopyridine, or other antiplatelet medication during the study period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM) [ Time Frame: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose ] 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. •Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN) [ Time Frame: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage) ] 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. ;Main Objective: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM) [ Time Frame: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose ] •Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN) [ Time Frame: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage) ] ;Secondary Objective: Pharmacokinetics: Area Under the Concen | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite [ Time Frame: Part A: 0.5, 1, 1.5, 2, 4 hours postdose ] AUC of prasugrel inactive metabolite(s) from time 0 up to the last sampling time of 4 hours postdose [AUC(0-tlast)]. Improvements in bioanalytical methodology enabled direct measurement of Pras-AM from plasma, obviating the need to estimate its concentration from inactive downstream metabolite(s). Thus, the AUC of prasugrel inactive metabolite(s) was not analyzed. •Number of Participants With Pain [ Time Frame: Part B: Baseline and Day14 ± 4 days postdose in each dosing period ] The number of participants who answered "yes" to the first question in the Sickle Cell Disease Pain (SCD) Questionnaire is reported. Question 1: In the past 2 weeks, did you experience any sickle cell pain? •Number of Participants With Hemorrhagic Events Requiring Medical Intervention [ Time Frame: Part B: Baseline up to Day 36 ] Hemorrhagic events were determined by the study investigator. Medical intervention was defined as any medical attention resulting in therapy or further investigation, as determined by a trained medical professional. ;Timepoint(s) of evaluation of this end point: 0.5, 1, 1.5, 2, 4 hours postdose | — |
Countries
United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed