An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults
Condition: Anemia, Sickle Cell
MeSH terms: Anemia, Sickle Cell
Intervention: Prasugrel
Intervention description: Oral, daily for 12 days
Intervention MeSH terms: Prasugrel Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.