NCT01178099已完成1 期
A Pharmacokinetic and Pharmacodynamic Assessment of Prasugrel in Healthy Adults and Adults With Sickle Cell Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) From Time of Dosing Through the Sampling Time of the Last Quantifiable Concentration [AUC(0-tlast)] for Prasugrel's Active Metabolite, R-138727
研究概览
简要总结
The purpose of this study is to measure the exposure to prasugrel's active metabolite and the pharmacodynamic effects of prasugrel treatment in people with Sickle Cell Disease (SCD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Are 50 to 100 kilograms (kg), inclusive, at the time of screening.
- •Have signed informed consent.
- •If female, agree to use a reliable method of birth control during the study or are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause.
- •Control Subjects - Are healthy adults as determined by medical history, physical examination, and other screening procedures.
- •Sickle cell disease (SCD) Subjects - Subjects on hydroxyurea must be on a stable dose for the 30 days prior to enrollment without signs of hematologic toxicity at screening.
- •SCD Subjects - Are adults with SCD (hemoglobin SS [HbSS], Hb S beta0 thalassemia, Hb SC or Hb S beta+ thalassemia genotype) without a diagnosis of acute vaso-occlusive crisis (VOC) requiring medical intervention in an emergency department, infusion center, or as an inpatient) within the month prior to screening.
排除标准
- •Have a concomitant medical illness (for example, terminal malignancy) that, in the opinion of the investigator, is associated with reduced survival over the expected treatment period (approximately 1 month).
- •Exhibit severe hepatic dysfunction (cirrhosis, portal hypertension, or alanine aminotransferase [ALT] for aspartate aminotransaminase [AST]≥3 times upper limit of normal [ULN]).
- •Exhibit severe renal dysfunction defined as Cockcroft-Gault creatinine clearance<30 milliliters per minute (ml/min), or requiring chronic dialysis. Creatine clearance = [(140-Age) * Mass (in kg)] \ [72 * Serum creatinine (in milligrams per deciliter [mg/dL])].
- •Exhibit any contraindication for antiplatelet therapy.
- •Have a history of intolerance or allergy to approved thienopyridines.
- •Exhibit any signs or symptoms of an infection.
- •Have a hematocrit <18%.
- •Exhibit any history of bleeding diathesis, bleeding requiring in-hospital treatment, or papillary necrosis.
- •Have active internal bleeding.
- •Have a history of spontaneous bleeding requiring in-hospital treatment.
- •Have gross hematuria or >300 red blood cells (RBC)/high-powered field (HPF) on urinalysis at the time of screening.
- •History of previous intraocular hemorrhage which required treatment with surgery or laser, or evidence of active intraocular haemorrhage.
- •Have a prior history of transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke or other intracranial hemorrhage.
- •Have a known history of intracranial neoplasm, arteriovenous malformation, or aneurysm.
- •Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding.
- •Have an international normalized ratio (INR) known to be >1.5 (INR testing not required for study entry).
- •Have had recent surgery (within 30 days prior to screening) or are scheduled to undergo surgery within the next 60 days.
- •Have a recent history of clinically significant menorrhagia.
- •Have used any aspirin, warfarin, or thienopyridine in the 10 days prior to enrollment.
- •Have used any non-aspirin non-steroidal anti-inflammatory drug (NSAID) in the 3 days prior to enrollment.
- •Anticipate using aspirin, warfarin, NSAID, thienopyridine or other antiplatelet agent during the study period.
- •Are women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
- •Regular use of drugs of abuse and/or unacceptable positive findings on urinary drug screening (a positive urinary drug screening for sleep inducers or pain medications in subjects with SCD will be considered as an acceptable finding).
- •Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
研究组 & 干预措施
Prasugrel
Experimental
Participants received a single 10 milligram (mg) dose on Day 1 (single dose [SD]), followed by either 5 mg/day (for participants<60 kilograms [kg]) or 7.5 mg/day (for participants≥60 kg) for an additional 11 days (multiple dose [MD]).
干预措施: Prasugrel (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) From Time of Dosing Through the Sampling Time of the Last Quantifiable Concentration [AUC(0-tlast)] for Prasugrel's Active Metabolite, R-138727
时间窗: Time of dosing up to 8 hours post-dose on Day 1 and Day 12
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.
Maximum Concentration (Cmax) of Prasugrel's Active Metabolite, R-138727
时间窗: Day 1, Day 12
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.
次要结局
- Change From Baseline in the Maximum Platelet Aggregation (MPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Baseline, Day 12)
- Area Under the Plasma Concentration-Time Curve (AUC) From Time of Dosing Through the Sampling Time of the Last Quantifiable Concentration [AUC(0-tlast)] of Prasugrel's Inactive Metabolites, R-95913, R-106583, and R-119251(Day 1, Day 12)
- Change From Baseline in the Residual Platelet Aggregation (RPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Baseline, Day 12)
- Inhibition of Platelet Aggregation (IPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Day 12)
- Change From Baseline in the Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Baseline, Day 12)
- Change From Baseline in the Residual Platelet Aggregation (RPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Baseline, Day 12)
- Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12(Day 12)
- Maximum Concentration (Cmax) of Prasugrel's Inactive Metabolites, R-95913, R-106583, and R-119251(Day 1, Day 12)
- Change From Baseline in the P2Y12 Reaction Units (PRU) Device Reported P2Y12 Percent Inhibition at Day 12(Baseline, Day 12)
- Change From Baseline in the Platelet Reactivity Index (PRI) of Prasugrel at Day 12(Baseline, Day 12)
- Change From Baseline in the Area Under the Aggregation Curve at Day 12(Baseline, Day 12)
- Change From Baseline in the Percent Aggregation to 20 µM Adenosine Diphosphate (ADP) at Day 12(Baseline, Day 12)
- P2Y12 Reaction Units (PRU)-Derived VerifyNow (VN) Percent Inhibition at Day 12(Day 12)
研究者
研究点 (1)
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