Prasugrel Versus Placebo in Adult Sickle Cell Disease

A Double-Blind, Randomized, Multicenter Study of Prasugrel Compared to Placebo in Adult Patients With Sickle Cell Disease

The purpose of this trial is to assess the safety of Prasugrel in adult patients with sickle cell disease (SCD) by monitoring the rate and severity of hemorrhagic events requiring medical intervention compared to placebo for 30 days.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Anemia
• Intervention / Treatment: Drug: Prasugrel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • 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.
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • 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.
  • California
    • Sacramento, California, United States, 95817
      • 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.
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • 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.
  • Georgia
    • Augusta, Georgia, United States, 30912
      • 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.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • 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.
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • 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.
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • 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.
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • 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.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • 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.
    • Greenville, North Carolina, United States, 27834
      • 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.
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • 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.
    • Pittsburgh, Pennsylvania, United States, 15224
      • 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.
  • Texas
    • Houston, Texas, United States, 77002
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults with Sickle Cell Disease (SCD).
• Are greater than or equal to 50 kilograms (kg) at time of screening.
• Are not currently being treated with an investigational drug (use of hydroxyurea, which is not an investigational drug, is permitted under this protocol if the patient has been on a stable dose for at least 30 days prior to randomization and has no signs of hematological toxicity at screening.
• 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.

Exclusion Criteria:

• Acute painful crisis (requiring medical attention) within 30 days prior to screening.
• 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 30 days).
• Severe hepatic dysfunction (cirrhosis, portal hypertension, or aspartate aminotransferase (AST) greater than or equal to 3x upper limit of normal [ULN]).
• Renal dysfunction requiring chronic dialysis.
• Contraindication for antiplatelet therapy.
• History of intolerance or allergy to approved thienopyridines.
• Have signs or symptoms of an infection.
• Hypertension (systolic blood pressure >180 millimeters of mercury (mm Hg) or diastolic blood pressure >110 mm Hg) at the time of screening or randomization.
• Hematocrit <18%.
• Any history of bleeding diathesis, bleeding requiring in-hospital treatment, or papillary necrosis.
• Active internal bleeding.
• History of spontaneous gastrointestinal (GI) bleeding requiring in-hospital treatment.
• Gross hematuria. Microhematuria, common in SCD patients, is not a contraindication.
• Platelet count <100,000 per cubic millimeter.
• Any history of intraocular hemorrhage.
• Prior history of transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, or other intracranial hemorrhage.
• 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) of greater than 1.5 at screening.
• Have had recent surgery (within 30 days prior to screening) or are scheduled to undergo surgery within the next 60 days.
• History of menorrhagia requiring medical intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Administered orally, once daily for 30 days.
Experimental: 7.5 mg Prasugrel; Participants were to receive 7.5 milligrams (mg) of prasugrel orally, once daily if they weighed ≥60 kilograms (kg) and if pharmacodynamic (PD) measures indicated that the 5-mg prasugrel dose did not produce a steady-state PD response equivalent to inhibition of platelet activation (IPA) ≥25%. Because these criteria were not met, no participants received 7.5 mg of prasugrel.	Drug: Prasugrel; Administered orally, once daily for 30 days.; Other Names: Effient; LY640315; Efient; CS747
Experimental: 5 mg Prasugrel	Drug: Prasugrel; Administered orally, once daily for 30 days.; Other Names: Effient; LY640315; Efient; CS747

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention During the Treatment Duration	A hemorrhagic event requiring medical intervention. Medical intervention was defined as any medical attention resulting in therapy or further investigation during the 30-day treatment duration.	Baseline through 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemorrhagic Treatment-Emergent Adverse Events (TEAEs) During the Treatment Duration	TEAEs were defined as AEs that occurred or worsened after receiving the study drug.	Baseline through 30 days
Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration	Participants recorded the intensity of pain due to SCD each day in the daily pain diaries. A scale of 0 to 9 was used, with 0 indicating no pain, and 9 indicating unbearable pain. A response range of 1 to 9 indicated the participant experienced pain due to SCD, whereas a response of 0 indicated participant did not experience pain due to SCD. The percentage of days with pain (pain rate) was calculated as follows: Pain rate = 100*(Total number of days with pain/number of daily pain diaries completed). Number of daily pain diaries completed was number of nonmissing pain intensity responses.	Baseline through 30 days
Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration	Pain requiring medical attention was defined 2 ways: (1) if the participant attended an unplanned doctor's appointment or clinic visit, visited the emergency room, or was admitted to hospital due to sickle cell pain, or (2) if the participant experienced a vaso-occlusive crisis (VOC), acute chest syndrome, or hepatic sequestration at least once during the treatment period.	Baseline through 30 days
Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days	PRI was calculated by VASP phosphorylation assay using flow cytometry. The PRI indicates the level of P2Y12 inhibition. A low PRI reflects strong inhibition of P2Y12, whereas a high PRI reflects weak/absent inhibition of P2Y12. The Least Squares (LS) Mean values were calculated from a mixed-effects model repeated measures (MMRM) analysis with baseline measurement, stratification variable sickle cell genotype, treatment, time, and time*treatment interaction as fixed effects, and participant as a random effect in the model.	30 days
Intensity of Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration	Participants recorded intensity of pain due to SCD each day in daily pain diaries using a pain scale. A scale of 0 to 9 was used, with 0=no pain and 9=unbearable pain. A response range of 1 to 9 indicated participant experienced pain due to SCD, whereas a response of 0 indicated participant did not experience pain due to SCD. Pain intensity was the average of a participant's pain ratings. Average pain intensity=(Sum of all nonmissing pain intensity responses/number of daily pain diaries completed). Number of daily pain diaries completed is number of nonmissing pain intensity responses.	Baseline through 30 days
P2Y12 Reaction Units (PRU) as Measured by Accumetrics VerifyNow® P2Y12 (VN P2Y12) at 30 Days	PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. The VN P2Y12 assay is a point-of-care device that measures platelet aggregation with single-use, disposable cartridges. A low PRU reflects stronger inhibition of P2Y12, whereas a high PRU reflects weaker inhibition of P2Y12. The Least Squares Mean values were calculated from a mixed-effects model repeated measures analysis with baseline measurement, stratification variable sickle cell genotype, treatment, time, and time*treatment interaction as fixed effects, and participant as a random effect in the model.	30 days

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: July 20, 2010
• First Submitted That Met QC Criteria: July 20, 2010
• First Posted (Estimate): July 21, 2010

Study Record Updates

• Last Update Posted (Estimate): May 3, 2012
• Last Update Submitted That Met QC Criteria: April 9, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Adult; Sickle Cell Disease; Sickle Cell Anemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: 13806; H7T-MC-TAEK (Other Identifier: Eli Lilly and Company)