A Study of Prasugrel in Pediatric Participants With Sickle Cell Disease (Crescent)

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01476696
First received: November 17, 2011
Last updated: January 17, 2014
Last verified: January 2014
Results First Received: October 18, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Sickle Cell Disease
Intervention: Drug: Prasugrel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study was conducted in 2 parts: Part A (single-dose range finding phase) then Part B (once-daily repeated dosing phase). Participants completing Part A could, but were not required to, participate in Part B. There were 2 dosing periods during Part B of the study.

Reporting Groups
  Description
Part A: Prasugrel Single Dose

Participants who only enrolled in Part A of the study.

Part A: 0.03 milligrams per kilogram (mg/kg) up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant in order to achieve desired platelet inhibition (20% to 50%). Single dose administered orally [oral-disintegrating tablet (ODT)] up to 3 times, at different mg/kg doses, with up to 18 days between doses.

Part B: Prasugrel Once-Daily Dose

Participants who only enrolled in Part B of the study.

Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period during Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then pharmacodynamic (PD) response measured 4 hours later. Based on 4-hour PD response, each participant assigned to either 0.08 or 0.06 mg/kg Prasugrel, administered orally, once daily for the remainder of the first dosing period in Part B. For the second continuous 14 ± 4-day period, participants were administered 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on their steady-state PD response at the end of the first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition. Participants received study drug for a total of 28 ± 8 days during Part B of the study.

Part A Then Part B: Prasugrel Single Dose Then Once-Daily Dose

Participants who enrolled in Part A and B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.

Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, such that the second dose would be unlikely to exceed 50% platelet inhibition.


Participant Flow:   Overall Study
    Part A: Prasugrel Single Dose     Part B: Prasugrel Once-Daily Dose     Part A Then Part B: Prasugrel Single Dose Then Once-Daily Dose  
STARTED     15     9     9  
Received at Least 1 Dose of Study Drug     15     9     9  
COMPLETED     12     8     9  
NOT COMPLETED     3     1     0  
Sponsor decision                 2                 1                 0  
Withdrawal by Subject                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants.

Reporting Groups
  Description
Entire Study Population

Participants enrolled in Part A, Part A and B, or only Part B of study. Part A: 0.03 up to 0.60 mg/kg Prasugrel, each dose titrated up or down for each participant to achieve desired platelet inhibition (20% to 50%). Single dose administered orally, ODT, up to 3 times, at different mg/kg doses, with up to 18 days between doses.

Part B: Daily Prasugrel dose (mg/kg) expected to achieve mean platelet activation inhibition of 30%, administered orally, ODT, once daily for 14 ± 4 days (first dosing period in Part B). Initial dose, 0.08 mg/kg Prasugrel, administered then PD response measured 4 hours later. Based on 4-hour PD response, each participant assigned to 0.08 or 0.06 mg/kg Prasugrel once daily for remainder of first dosing period. For second 14 ± 4-day period, participants assigned to 1 of 3 possible doses: 0.06, 0.08, or 0.12 mg/kg depending on steady-state PD response at end of first dosing period, so that the second dose would be unlikely to exceed 50% platelet inhibition.


Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  33  
Age, Customized  
[units: participants]
 
≥2 and ≤5 years     7  
≥6 and ≤11 years     14  
≥12 and ≤17 years     12  
Gender  
[units: participants]
 
Female     19  
Male     14  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     1  
Not Hispanic or Latino     32  
Unknown or Not Reported     0  
Race/Ethnicity, Customized  
[units: participants]
 
Native Hawaiian or Other Pacific Islander     1  
Black or African American     32  
Region of Enrollment  
[units: participants]
 
United States     33  
Height  
[units: centimeters (cm)]
Mean ± Standard Deviation
  139.21  ± 22.663  
Weight  
[units: kilograms (kg)]
Mean ± Standard Deviation
  38.55  ± 18.785  
Body Mass Index [1]
[units: kilograms per square meter (kg/m^2)]
Mean ± Standard Deviation
  18.64  ± 4.091  
Genotype [2]
[units: participants]
 
HbSS     30  
HbS Beta^0 Thalassemia     3  
[1] Body mass index is an estimate of body fat based on body weight divided by height squared.
[2] The number of participants who have the homozygous sickle cell (HbSS) or hemoglobin S beta^0 thalassemia (HbS β^0 thalassemia)] sickle cell genotype.



  Outcome Measures
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1.  Primary:   Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)   [ Time Frame: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose ]

2.  Primary:   Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)   [ Time Frame: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage) ]

3.  Secondary:   Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite   [ Time Frame: Part A: 0.5, 1, 1.5, 2, 4 hours postdose ]

4.  Secondary:   Number of Participants With Pain   [ Time Frame: Part B: Baseline and Day14 ± 4 days postdose in each dosing period ]

5.  Secondary:   Number of Participants With Hemorrhagic Events Requiring Medical Intervention   [ Time Frame: Part B: Baseline up to Day 36 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Data for the Primary Outcome Measures 1 and 2 were collected for presentation of results in a scatter plot and were not intended to be summarized due to the limited number of participants per treatment.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01476696     History of Changes
Other Study ID Numbers: 12324, H7T-MC-TACX
Study First Received: November 17, 2011
Results First Received: October 18, 2013
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration