An Assessment of Prasugrel on Healthy Adults and Sickle Cell Adults

NCT01178099 | Completed Phase 1 Results

• 2 other identifiers: 13746H7T-MC-TAEJ
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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).

Conditions

Anemia, Sickle Cell

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Time of dosing up to 8 hours post-dose on Day 1 and Day 12

• Maximum Concentration (Cmax) of Prasugrel's Active Metabolite, R-138727

  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.

  Day 1, Day 12

Secondary Outcomes (13)

• 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

Study Arms (1)

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 \[MD\]).

Drug: Prasugrel

Interventions

Prasugrel DRUG

Oral, daily for 12 days

Also known as: LY650315, CS747, Effient, Efient

Prasugrel

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Daiichi Sankyo Co., Ltd.: collaborator

Study Sites (1)

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.

London, UK, SE 1 1YR, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2010
• First Posted: August 9, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: February 15, 2012
• Results First Posted: February 15, 2012

Record last verified: 2012-01

Locations

GB (1)