An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults

Lilly

Status and phase: Completed; Phase 1

Conditions: Anemia, Sickle Cell

Treatments: Drug: Prasugrel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01178099

H7T-MC-TAEJ (Other Identifier)

13746

Details and patient eligibility

About

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).

Enrollment: 26 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 1 patient group

Prasugrel

Experimental group

Description:

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 \[MD\]).

Treatment:

Drug: Prasugrel