Prasugrel Versus Placebo in Adult Sickle Cell Disease

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01167023
First received: July 20, 2010
Last updated: April 9, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Sickle Cell Anemia
Drug: Prasugrel
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Multicenter Study of Prasugrel Compared to Placebo in Adult Patients With Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention During the Treatment Duration [ Time Frame: Baseline through 30 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Hemorrhagic Treatment-Emergent Adverse Events (TEAEs) During the Treatment Duration [ Time Frame: Baseline through 30 days ] [ Designated as safety issue: Yes ]
    TEAEs were defined as AEs that occurred or worsened after receiving the study drug.

  • Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration [ Time Frame: Baseline through 30 days ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration [ Time Frame: Baseline through 30 days ] [ Designated as safety issue: No ]
    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.

  • Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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.

  • Intensity of Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration [ Time Frame: Baseline through 30 days ] [ Designated as safety issue: No ]
    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.

  • P2Y12 Reaction Units (PRU) as Measured by Accumetrics VerifyNow® P2Y12 (VN P2Y12) at 30 Days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 62
Study Start Date: July 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Efient
  • Effient
  • LY640315
  • CS747
Placebo Comparator: Placebo Drug: Placebo
Administered orally, once daily for 30 days.
Experimental: 5 mg Prasugrel Drug: Prasugrel
Administered orally, once daily for 30 days.
Other Names:
  • Efient
  • Effient
  • LY640315
  • CS747

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01167023

Locations
United States, Alabama
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.
Birmingham, Alabama, United States, 35205
United States, Arkansas
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.
Little Rock, Arkansas, United States, 72211
United States, California
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.
Sacramento, California, United States, 95817
United States, Florida
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.
Daytona Beach, Florida, United States, 32117
United States, Georgia
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Augusta, Georgia, United States, 30912
United States, Indiana
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.
Indianapolis, Indiana, United States, 46260
United States, Maryland
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.
Baltimore, Maryland, United States, 21205
United States, Massachusetts
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.
Boston, Massachusetts, United States, 02118
United States, Mississippi
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.
Jackson, Mississippi, United States, 39216
United States, North Carolina
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.
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
United States, Pennsylvania
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.
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
United States, Texas
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.
Houston, Texas, United States, 77002
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo Inc.
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01167023     History of Changes
Other Study ID Numbers: 13806, H7T-MC-TAEK
Study First Received: July 20, 2010
Results First Received: April 9, 2012
Last Updated: April 9, 2012
Health Authority: United States: Food and Drug Administration
Canada: Canadian Institutes of Health Research
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Eli Lilly and Company:
Sickle Cell Disease
Sickle Cell Anemia
Adult

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Prasugrel
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists

ClinicalTrials.gov processed this record on October 23, 2014