Clinical trial NCT01178099: An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults
Official title: A Pharmacokinetic and Pharmacodynamic Assessment of Prasugrel in Healthy Adults and Adults With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anemia, Sickle Cell
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
First posted: 2010-08-09
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Primary outcomes:
measure: 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
timeFrame: Time of dosing up to 8 hours post-dose on Day 1 and Day 12
measure: Maximum Concentration (Cmax) of Prasugrel's Active Metabolite, R-138727
timeFrame: Day 1, Day 12
Secondary outcomes:
measure: Change From Baseline in the Maximum Platelet Aggregation (MPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Baseline, Day 12
measure: 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
timeFrame: Day 1, Day 12
measure: Change From Baseline in the Residual Platelet Aggregation (RPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Baseline, Day 12
measure: Inhibition of Platelet Aggregation (IPA) to 5 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Day 12
measure: Change From Baseline in the Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Baseline, Day 12
measure: Change From Baseline in the Residual Platelet Aggregation (RPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Baseline, Day 12
measure: Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12
timeFrame: Day 12
measure: Maximum Concentration (Cmax) of Prasugrel's Inactive Metabolites, R-95913, R-106583, and R-119251
timeFrame: Day 1, Day 12
measure: Change From Baseline in the P2Y12 Reaction Units (PRU) Device Reported P2Y12 Percent Inhibition at Day 12
timeFrame: Baseline, Day 12
measure: Change From Baseline in the Platelet Reactivity Index (PRI) of Prasugrel at Day 12
timeFrame: Baseline, Day 12
measure: Change From Baseline in the Area Under the Aggregation Curve at Day 12
timeFrame: Baseline, Day 12
measure: Change From Baseline in the Percent Aggregation to 20 µM Adenosine Diphosphate (ADP) at Day 12
timeFrame: Baseline, Day 12
measure: P2Y12 Reaction Units (PRU)-Derived VerifyNow (VN) Percent Inhibition at Day 12
timeFrame: Day 12
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: UK
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317 615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: