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Clinical Trial Results:
A Phase 3, Double-Blind, Randomized, Efficacy and Safety Comparison of Prasugrel and Placebo in Pediatric Patients with Sickle Cell Disease.

Summary
EudraCT number	2012-003837-41
Trial protocol	GB BE NL IT
Global end of trial date	17 Dec 2015

Results information
Results version number	v1(current)
This version publication date	01 Jul 2016
First version publication date	01 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

13038

ISRCTN number

US NCT number

NCT01794000

WHO universal trial number (UTN)

Other trial identifiers

Trial Alias: H7T-MC-TADO, Trial Number: 13038

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-CTLilly,

Scientific contact

Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-285-4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

17 Dec 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Dec 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

The main purpose of the study is to evaluate the efficacy/safety of prasugrel as monotherapy for reduction of Vaso Occlusive Crisis in patients aged 2 to less than 18 years. The statistical analysis plan allowed for data cutoff on 17-Jul-2015. This was designated the submission data base lock which occurred Aug-2015 and patients continued study drug to garner more safety data (to inform labeling should the study have been positive). A review of the efficacy/safety by the Sponsors mid Sep-2015 confirmed a lack of efficacy with no new safety issues; patients were then contacted starting on 17-Sep-2015, and taken off of study drug. Almost all patients discontinued study drug by 1-Oct-2015, with follow up for study close out continuing until late 2015, and allowing for the 120 day safety assessment data lock in late Jan-2016.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Apr 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 48

Country: Number of subjects enrolled

Egypt: 45

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

Ghana: 57

Country: Number of subjects enrolled

Kenya: 91

Country: Number of subjects enrolled

Oman: 6

Country: Number of subjects enrolled

Lebanon: 16

Country: Number of subjects enrolled

Saudi Arabia: 1

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Turkey: 42

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

Brazil: 1

Country: Number of subjects enrolled

Italy: 14

Worldwide total number of subjects

341

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

199

Adolescents (12-17 years)

142

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Text not entered

Period 1 title

Double-Blind Phase (DBP)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

Prasugrel

Arm description

Participants will be titrated from initial daily dose of 0.08 milligram per kilogram (mg/kg) of orally administered prasugrel monotherapy at randomization to a dose that will achieve a P2Y12 reaction units (PRU) level of 231 to 136, as measured by VerifyNow instrument. This corresponds to a range of platelet inhibition of approximately 30% to 60%. The maximum possible dose allowed is 0.12 mg/kg daily, not to exceed 10 mg daily.

Arm type

Experimental

Investigational medicinal product name

Prasugrel

Investigational medicinal product code

Other name

LY640315, Effient, Efient

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Placebo

Arm description

Participants in this treatment group will receive daily orally administered placebo after being mock titrated in a fashion identical to the active treatment group.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Participants in this treatment group will receive daily orally administered placebo after being mock titrated in a fashion identical to the active treatment group.

Number of subjects in period 1	Prasugrel	Placebo
Started	171	170
Received at least one dose of drug	170	170
Discontinued During Double Blind Phase	169	166
Completed	2	4
Not completed	169	166
Adverse event, serious fatal	1	2
Parent/Caregiver Decision	5	2
Physician decision	2	-
Consent withdrawn by subject	6	11
Adverse event, non-fatal	5	2
Sponsor Decision	148	149
Entry Criteria Not Met	2	-

Period 2 title

Open-Label Extension Phase (OLE)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Prasugrel (OLE)

Arm description

Participants who continued to meet eligibility criteria, who were not permanently discontinued from study drug, and who concluded their participation in 24 months of double blind treatment were to be considered eligible to enter the open label phase.

Arm type

Experimental

Investigational medicinal product name

Prasugrel

Investigational medicinal product code

Other name

LY640315, Effient, Efient

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Participants who were on placebo during the double-blind treatment period will begin the OLE titration with the 0.08-mg/kg dose. The participants who had been on prasugrel will start the OLE on their final double-blind dose, which may be titrated up or down as required. Similar to the double-blind treatment period, doses will be adjusted to reach the target level of platelet inhibition. The maximum level of platelet inhibition that will be allowed in this study will be approximately 60% (corresponding to a PRU of 136). Any patient with a PRU less than 136 during the titration period who cannot be titrated to a lower dose will be discontinued from the study.

Number of subjects in period 2 ^[1]	Prasugrel (OLE)
Started	3
Completed	0
Not completed	3
Sponsor Decision	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who had not permanently discontinued study drug, completed 24 months of treatment and met OLE criteria were eligible to enter OLE.

Baseline characteristics

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Reporting group title

Prasugrel

Reporting group description

Reporting group title

Placebo

Reporting group description

Participants in this treatment group will receive daily orally administered placebo after being mock titrated in a fashion identical to the active treatment group.

Reporting group values	Prasugrel	Placebo	Total
Number of subjects	171	170	341
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age Continuous
Units: years
arithmetic mean (standard deviation)	10.606 ( 4.334 )	10.58 ( 4.349 )	-
Gender, Male/Female
Units: participants
Female	87	86	173
Male	84	84	168
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	2	1	3
Not Hispanic or Latino	94	98	192
Unknown or Not Reported	75	71	146
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	113	109	222
White	58	58	116
More than one race	0	2	2
Unknown or Not Reported	0	1	1
Region of Enrollment
Units: Subjects
United States	23	25	48
Egypt	23	22	45
United Kingdom	5	4	9
Ghana	29	28	57
Kenya	47	44	91
Oman	2	4	6
Lebanon	8	8	16
Saudi Arabia	1	0	1
Canada	4	4	8
Turkey	20	22	42
Belgium	1	2	3
Brazil	1	0	1
Italy	7	7	14
Hydroxyurea Use at Baseline
Units: Subjects
Yes	77	76	153
No	94	94	188

End points

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Reporting group title

Prasugrel

Reporting group description

Reporting group title

Placebo

Reporting group description

Participants in this treatment group will receive daily orally administered placebo after being mock titrated in a fashion identical to the active treatment group.

Reporting group title

Prasugrel (OLE)

Reporting group description

Subject analysis set title

Prasugrel - Validadated Faces Pain Scale-Revised Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who are 7 years or older and have both baseline and at least one post-baseline monthly outcome measure in any month. This is the Sickle cell population in which content validity has been established for the Faces Pain Scale-Revised (FPS-R).

Subject analysis set title

Placebo - Validadated Faces Pain Scale-Revised Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Number of Vaso-Occlusive Crisis (VOC) Events per Participant per Year (Rate of VOC)

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End point title

Number of Vaso-Occlusive Crisis (VOC) Events per Participant per Year (Rate of VOC)

End point description

The VOC is a composite endpoint of painful crisis or acute chest syndrome. Events that occurred within 7 days from the prior event onset date were not counted as a new episode. Data collected through the primary completion date reported below.

End point type

Primary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[1]	170 ^[2]
Units: Number of Events per Participant-Year
number (not applicable)	2.295	2.767

Notes
[1] - All randomized participants.
[2] - All randomized participants.

Rate of Vaso-Occlusive Crisis

Statistical analysis description

The time to a recurrent episode of VOC was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model.

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.117

Method

Andersen-Gill model

Parameter type

Rate Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.05

Notes
[3] - The time to a recurrent episode of VOC was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model. The rate ratio and 2-sided 95% Confidence Interval (CI) were estimated from the Andersen-Gill model.

Secondary: Monthly Rate of Days with Pain

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End point title

Monthly Rate of Days with Pain

End point description

Monthly rate of days with pain was measured through participant diaries using a modified version of the FPS-R. Each day participants selected the face on the scale that reflected their worst pain related to sickle cell disease (SCD) on that day. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. Any day the participant selected a face other than face 0 was considered a day with pain. Monthly rate of days with pain was calculated for each participant by summing the number of days reported with any pain divided by the number of non-missing diary entries completed in the month. A month was defined as 4 weeks (28 days).The monthly rate was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are present below.

End point type

Secondary

End point timeframe

Randomization through 9 Months

End point values	Prasugrel - Validadated Faces Pain Scale-Revised Population	Placebo - Validadated Faces Pain Scale-Revised Population
Number of subjects analysed	127	127
Units: Percentage of Days in a Month
least squares mean (standard error)	17.457 ( 1.558 )	17.699 ( 1.551 )

Monthly Rate of Days with Pains

Comparison groups

Prasugrel - Validadated Faces Pain Scale-Revised Population v Placebo - Validadated Faces Pain Scale-Revised Population

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.912

Method

Mixed models analysis

Parameter type

Least Square Mean Difference

Point estimate

-0.242

Confidence interval

level

95%

sides

2-sided

lower limit

-4.564

upper limit

4.079

Notes
[4] - Mixed Model Repeated Measures (MMRM) included fixed effects of treatment, baseline value of the pain-diary outcome measure, hydroxyurea use, age group, time and treatment-by-time interaction. The Least Square (LS) Mean difference of prasugrel minus placebo and the corresponding 2-sided 95% CI were estimated from the MMRM model.

Secondary: Monthly Mean in Faces Pain Scale-Revised Score

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End point title

Monthly Mean in Faces Pain Scale-Revised Score

End point description

Each day participants selected the face on the FPS-R scale that reflected their worst pain related to sickle cell disease (SCD) on that day. Monthly mean in FPS-R score was calculated for each participant by summing the FPS-R score divided by the number of non-missing diary entries completed in the month. This pain scale contains six faces corresponding to the pain intensity of 0, 2, 4, 6, 8 or 10, in which 0 denotes no pain and 10 denotes the worst pain possible. A month was defined as 4 weeks (28 days). The monthly mean in FPS-R score was set to missing if there were more than 14 missing entries for the FPS-R in a specific month. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 9 Months

End point values	Prasugrel - Validadated Faces Pain Scale-Revised Population	Placebo - Validadated Faces Pain Scale-Revised Population
Number of subjects analysed	127	127
Units: Units on a Scale
least squares mean (standard error)	0.7116 ( 0.0757 )	0.6148 ( 0.0753 )

Monthly Mean in Faces Pain Scale-Revised Score

Comparison groups

Prasugrel - Validadated Faces Pain Scale-Revised Population v Placebo - Validadated Faces Pain Scale-Revised Population

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.365

Method

Mixed models analysis

Parameter type

Least Square Mean Difference

Point estimate

0.0968

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1132

upper limit

0.3068

Notes
[5] - MMRM model included fixed effects of treatment, baseline value of the pain-diary outcome measure, hydroxyurea use, age group, time and treatment-by-time interaction. The LS Mean difference of prasugrel minus placebo and the corresponding 2-sided 95% CI were estimated from the MMRM model. The rate ratio and 2-sided 95% CI were estimated from the Andersen-Gill model.

Secondary: Number of Painful Crisis Events per Participant per Year (Rate of Painful Crisis)

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End point title

Number of Painful Crisis Events per Participant per Year (Rate of Painful Crisis)

End point description

A painful crisis is defined as an onset of moderate to severe pain that lasts at least 2 hours for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, ketorolac, or other analgesics prescribed by a health care provider (HCP) in a medical setting such as a hospital, clinic, emergency room visit, or telephone management. The painful crisis that occurred within 7 days from the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[6]	170 ^[7]
Units: Number of Events per Participant-Year
number (not applicable)	2.239	2.72

Notes
[6] - All randomized participants.
[7] - All randomized participants.

Rate of Painful Crisis

Statistical analysis description

The time to a recurrent episode of painful crisis was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model.

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.109

Method

Andersen-Gill Model

Parameter type

Rate Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.04

Secondary: Number of Hospitalizations for VOC per Participant per Year (Rate of Hospitalizations)

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End point title

Number of Hospitalizations for VOC per Participant per Year (Rate of Hospitalizations)

End point description

Hospitalization that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[8]	170 ^[9]
Units: Number of Events per Participant-Year
number (not applicable)	1.064	1.126

Notes
[8] - All randomized participants.
[9] - All randomized participants.

Rate of Hospitalizations

Statistical analysis description

The time to a recurrent episode of hospitalization was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model. The rate ratio and 2-sided 95% CI were estimated from the Andersen-Gill model.

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.759

Method

Andersen-Gill model

Parameter type

Rate Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.37

Secondary: Number of Acute Chest Syndrome per Participant per Year (Rate of Acute Chest Syndrome)

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End point title

Number of Acute Chest Syndrome per Participant per Year (Rate of Acute Chest Syndrome)

End point description

Acute chest syndrome was defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray. Acute chest syndrome that occurred within 7 days of the prior event onset date was not counted as a new episode. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[10]	170 ^[11]
Units: Number of Events per Participant-Year
number (not applicable)	0.112	0.115

Notes
[10] - All randomized participants.
[11] - All randomized participants.

Rate of Acute Chest Syndrome

Statistical analysis description

The time to a recurrent episode of acute chest syndrome was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model.

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.916 ^[13]

Method

Andersen-Gill model

Parameter type

Rate Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.93

Notes
[12] - The time to a recurrent episode of acute chest syndrome was analyzed using Andersen-Gill model. A robust variance estimate was used, with treatment, hydroxyurea use at baseline and age group included as factors in the model. The rate ratio and 2-sided 95% CI were estimated from the Andersen-Gill model.
[13] - The time to a recurrent episode of acute chest syndrome was analyzed using Andersen-Gill model.

Secondary: Number of Red Blood Cell (RBC) Transfusions due to Sickle Cell Disease (SCD) per Participant per Year (Rate of RBC Transfusions)

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End point title

Number of Red Blood Cell (RBC) Transfusions due to Sickle Cell Disease (SCD) per Participant per Year (Rate of RBC Transfusions)

End point description

RBC transfusions that occurred within 7 days of the prior event onset date were not counted as a new episode. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[14]	170 ^[15]
Units: Number of Events per Participant-Year
number (not applicable)	0.497	0.42

Notes
[14] - All randomized participants.
[15] - All randomized participants.

Rate of RBC Transfusions

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.544 ^[16]

Method

Andersen-Gill model

Parameter type

Rate Ratio

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.91

Notes
[16] - The time to a recurrent episode of RBC transfusion was analyzed using Andersen-Gill model. The rate ratio and 2-sided 95% CI were estimated from the Andersen-Gill model.

Secondary: Monthly Rate of Days of Analgesic Use

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End point title

Monthly Rate of Days of Analgesic Use

End point description

Monthly rate of days of analgesic use was measured through participant diaries and was calculated for each participant by summing the number of days they reported analgesic use divided by the number of diary entries completed in the month. A month was defined as 4 weeks (28 days). The monthly rate was set to missing if there were more than 14 missing entries for analgesic use in a specific month. Data collected through the primary completion date are presented below. Analysis Population: All randomized participants who are 4 years or older and have baseline and at least one post-baseline monthly outcome measure in any month. Diaries were only provided to participants 4 years and older.

End point type

Secondary

End point timeframe

Randomization through 9 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	153	153
Units: Percentage of Days in a Month
least squares mean (standard error)	24.27 ( 2.29 )	22.757 ( 2.337 )

Monthly Rate of Days of Analgesic Use

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

= 0.602 ^[18]

Method

Mixed models analysis

Parameter type

Least Square Mean Difference

Point estimate

1.513

Confidence interval

level

95%

sides

2-sided

lower limit

-4.186

upper limit

7.213

Notes
[17] - The MMRM model included the fixed effects of treatment, the baseline value of the pain-diary measure, hydroxyurea use, age group, time and treatment-by-time interaction. The Least Square Mean difference of prasugrel minus placebo and the corresponding 2-sided 95% CI were estimated from the MMRM model.
[18] - The MMRM model included the fixed effects of treatment, the baseline value of the pain-diary measure, hydroxyurea use, age group, time and treatment-by-time interaction.

Secondary: Quarterly Rate of School Absence due to Sickle Cell Pain

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End point title

Quarterly Rate of School Absence due to Sickle Cell Pain

End point description

Quarterly rate of school absence due to sickle cell pain was measured through participant diaries and was calculated for each participant by summing the number of days with school absence due to sickle cell pain divided by the number of school dates in the quarter. A quarter was defined as 12 weeks. The quarterly rate was set to missing if there were more than 6 weeks of missing diary entries during a specific quarter. Data collected through the primary completion date are presented below. Analysis Population: All Randomized participants who are 4 years or older and have both baseline and at least one post-baseline quarterly outcome measure in any quarter. Diaries were only provided to participants 4 years and older.

End point type

Secondary

End point timeframe

Randomization through 9 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	105	115
Units: Percentage of Days in a Quarter
least squares mean (standard error)	11.527 ( 1.525 )	10.255 ( 1.466 )

Rate of School Absence due to Sickle Cell Pain

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other ^[19]

P-value

= 0.459

Method

Mixed models analysis

Parameter type

Least Square Mean Difference

Point estimate

1.272

Confidence interval

level

95%

sides

2-sided

lower limit

-2.109

upper limit

4.652

Notes
[19] - The MMRM model included the fixed effects of treatment, the baseline value of the pain-diary measure, hydroxyurea use, age group, time and treatment-by-time interaction. The LS Mean difference of prasugrel minus placebo and the corresponding 2-sided 95% CI were estimated from the MMRM model.

Secondary: Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke

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End point title

Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke

End point description

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	0 ^[20]	0 ^[21]
Units: Percentage of Participants
number (not applicable)

Notes
[20] - No participants had a TIA or ischemic stroke at time of analysis.
[21] - No participants had a TIA or ischemic stroke at time of analysis.

No statistical analyses for this end point

Secondary: Number of Days Hospitalized for VOC

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End point title

Number of Days Hospitalized for VOC

End point description

The total length of hospitalization in days for VOC was calculated for each participant. Data collected through the primary completion date are presented below.

End point type

Secondary

End point timeframe

Randomization through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	69 ^[22]	76 ^[23]
Units: Days
least squares mean (standard error)	12.9 ( 1.72 )	12 ( 1.63 )

Notes
[22] - All randomized participants who were hospitalized for VOC.
[23] - All randomized participants who were hospitalized for VOC.

Number of Days Hospitalized for VOC

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.662 ^[24]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

5.19

Notes
[24] - The ANCOVA model included the factors of treatment, hydroxyurea use, age group, and length of follow-up. The LS Mean difference of prasugrel minus placebo and 2-sided 95% CI were estimated from the ANCOVA model.

Secondary: Time from Randomization to First and Second VOC

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End point title

Time from Randomization to First and Second VOC

End point description

Data collected through the primary completion date are presented below. 99999999 = Data Not Available - Upper limit of 95% Confidence Interval could not be calculated due to limited data

End point type

Secondary

End point timeframe

Randomization to First VOC and Second VOC respectively (up to 24 Months)

End point values	Prasugrel	Placebo
Number of subjects analysed	171 ^[25]	170 ^[26]
Units: Days
median (confidence interval 95%)
Time from Randomization to the First VOC	90 (71 to 151)	87 (65 to 106)
Time from Randomization to the Second VOC	338 (240 to 99999999)	238 (177 to 300)

Notes
[25] - All randomized participants.
[26] - All randomized participants.

Time from Randomization to the First VOC

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.317

Method

Logrank

Confidence interval

Notes
[27] - A stratified log-rank test were performed with hydroxyurea use and age group as the stratification factors.

Time from Randomization to the Second VOC

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0.133

Method

Logrank

Confidence interval

Notes
[28] - A stratified log-rank test were performed with hydroxyurea use and age group as the stratification factors.

Secondary: Percentage of Participants with Hemorrhagic Events Requiring Medical Intervention

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End point title

Percentage of Participants with Hemorrhagic Events Requiring Medical Intervention

End point description

Medical intervention was defined as any medical evaluation resulting in therapy or further investigation, as determined by a trained medical professional. Data collected from the first dose of study medication through 10 days after last dose of study medication during the double blind study period are presented below.

End point type

Secondary

End point timeframe

First Dose through 24 Months

End point values	Prasugrel	Placebo
Number of subjects analysed	170 ^[29]	170 ^[30]
Units: Percentage of Participants
number (not applicable)	6.5	4.7

Notes
[29] - All randomized participants who received at least one dose of drug.
[30] - All randomized participants who received at least one dose of drug.

Percentage of Participants with Hemorrhagic Events

Comparison groups

Prasugrel v Placebo

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.638

Method

Fisher exact

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events reported below reflect the entire study safety information through the supplemental data base lock (the study completion date).

Adverse event reporting additional description

All randomized participants who received at least one dose of drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Prasugrel - Double Blind Phase

Reporting group description

Reporting group title

Placebo - Double Blind Phase

Reporting group description

Participants in this treatment group will receive daily orally administered placebo and will follow visit schedule identical to that in the active treatment group.

Reporting group title

Prasugrel - Open Label Phase

Reporting group description

Serious adverse events	Prasugrel - Double Blind Phase	Placebo - Double Blind Phase	Prasugrel - Open Label Phase
Total subjects affected by serious adverse events
subjects affected / exposed	100 / 170 (58.82%)	106 / 170 (62.35%)	0 / 3 (0.00%)
number of deaths (all causes)	1	2	0
number of deaths resulting from adverse events	0	0	0
Vascular disorders
deep vein thrombosis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
haematoma
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 2	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
nail operation
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
selective abortion
alternative dictionary used: MedDRA 18.1
subjects affected / exposed ^[1]	1 / 87 (1.15%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
chest pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
multi-organ failure
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
non-cardiac chest pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pyrexia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	5 / 170 (2.94%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
anaphylactic reaction
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
amenorrhoea
alternative dictionary used: MedDRA 18.1
subjects affected / exposed ^[2]	1 / 87 (1.15%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
priapism
alternative dictionary used: MedDRA 18.1
subjects affected / exposed ^[3]	0 / 170 (0.00%)	2 / 84 (2.38%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
thrombosis corpora cavernosa
alternative dictionary used: MedDRA 18.1
subjects affected / exposed ^[4]	0 / 170 (0.00%)	1 / 84 (1.19%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
acute chest syndrome
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	15 / 170 (8.82%)	14 / 170 (8.24%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 16	0 / 16	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
asthma
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
epistaxis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 2	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
lung disorder
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pleural effusion
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumothorax
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pulmonary hypertension
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
suicidal ideation
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
haemoglobin decreased
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
platelet count decreased
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
platelet count increased
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
serum ferritin increased
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
contusion
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
fall
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hand fracture
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
humerus fracture
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
lower limb fracture
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
thermal burn
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
cardiac failure
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
tachycardia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
haemorrhage intracranial
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
headache
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ruptured cerebral aneurysm
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	17 / 170 (10.00%)	20 / 170 (11.76%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 34	0 / 23	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
haemolysis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	3 / 170 (1.76%)	3 / 170 (1.76%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hypersplenism
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	3 / 170 (1.76%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
intravascular haemolysis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
sickle cell anaemia with crisis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	75 / 170 (44.12%)	83 / 170 (48.82%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	2 / 187	0 / 202	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
splenic infarction
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
thrombocytopenia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
thrombotic thrombocytopenic purpura
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
vertigo
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
disorder of orbit
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
abdominal pain upper
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
constipation
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
diarrhoea
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
enteritis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
gastritis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
gingival bleeding
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
cholelithiasis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hepatic sequestration
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hyperbilirubinaemia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
ecchymosis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
purpura
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
renal papillary necrosis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
inappropriate antidiuretic hormone secretion
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
back pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
dactylitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
musculoskeletal chest pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pain in extremity
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
abscess limb
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
acinetobacter bacteraemia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
acute sinusitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
adenovirus infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
arthritis bacterial
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
atypical pneumonia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
bacterial infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
bronchitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
cellulitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
cellulitis orbital
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
corona virus infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
enterovirus infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
gastroenteritis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hepatitis a
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hepatitis c
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
influenza
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	3 / 170 (1.76%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
lower respiratory tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
malaria
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	11 / 170 (6.47%)	11 / 170 (6.47%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 12	0 / 14	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
mastoiditis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
nasopharyngitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
osteomyelitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
osteomyelitis acute
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
osteomyelitis chronic
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
otitis media
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
parvovirus b19 infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pharyngitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pharyngitis streptococcal
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pilonidal cyst
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
plasmodium falciparum infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	6 / 170 (3.53%)	4 / 170 (2.35%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	6 / 170 (3.53%)	7 / 170 (4.12%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 7	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pneumonia streptococcal
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
pyomyositis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
respiratory syncytial virus bronchiolitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
respiratory syncytial virus infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
respiratory tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	4 / 170 (2.35%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
septic shock
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
sinusitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
staphylococcal sepsis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
tonsillitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	4 / 170 (2.35%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
tooth abscess
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	0 / 170 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
tooth infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
upper respiratory tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
urinary tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	2 / 170 (1.18%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
viral infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	1 / 170 (0.59%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
viral tonsillitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
viral upper respiratory tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	2 / 170 (1.18%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
dehydration
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hypoglycaemia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	1 / 170 (0.59%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Prasugrel - Double Blind Phase	Placebo - Double Blind Phase	Prasugrel - Open Label Phase
Total subjects affected by non serious adverse events
subjects affected / exposed	148 / 170 (87.06%)	154 / 170 (90.59%)	1 / 3 (33.33%)
Nervous system disorders
headache
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	25 / 170 (14.71%)	29 / 170 (17.06%)	0 / 3 (0.00%)
occurrences all number	32	43	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	6 / 170 (3.53%)	11 / 170 (6.47%)	0 / 3 (0.00%)
occurrences all number	8	13	0
sickle cell anaemia with crisis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	90 / 170 (52.94%)	102 / 170 (60.00%)	1 / 3 (33.33%)
occurrences all number	223	272	1
General disorders and administration site conditions
nodule
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	0 / 170 (0.00%)	0 / 170 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1
pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	18 / 170 (10.59%)	19 / 170 (11.18%)	0 / 3 (0.00%)
occurrences all number	31	30	0
pyrexia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	35 / 170 (20.59%)	43 / 170 (25.29%)	1 / 3 (33.33%)
occurrences all number	54	69	1
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	17 / 170 (10.00%)	20 / 170 (11.76%)	0 / 3 (0.00%)
occurrences all number	23	28	0
abdominal pain upper
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	3 / 170 (1.76%)	11 / 170 (6.47%)	0 / 3 (0.00%)
occurrences all number	3	14	0
constipation
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	9 / 170 (5.29%)	12 / 170 (7.06%)	0 / 3 (0.00%)
occurrences all number	10	16	0
diarrhoea
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	6 / 170 (3.53%)	11 / 170 (6.47%)	0 / 3 (0.00%)
occurrences all number	8	12	0
gastritis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	10 / 170 (5.88%)	10 / 170 (5.88%)	0 / 3 (0.00%)
occurrences all number	13	19	0
vomiting
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	7 / 170 (4.12%)	12 / 170 (7.06%)	0 / 3 (0.00%)
occurrences all number	11	19	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	14 / 170 (8.24%)	17 / 170 (10.00%)	1 / 3 (33.33%)
occurrences all number	19	19	1
epistaxis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	23 / 170 (13.53%)	21 / 170 (12.35%)	0 / 3 (0.00%)
occurrences all number	48	29	0
oropharyngeal pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	9 / 170 (5.29%)	8 / 170 (4.71%)	0 / 3 (0.00%)
occurrences all number	13	8	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	8 / 170 (4.71%)	10 / 170 (5.88%)	0 / 3 (0.00%)
occurrences all number	11	11	0
back pain
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	20 / 170 (11.76%)	29 / 170 (17.06%)	0 / 3 (0.00%)
occurrences all number	32	54	0
pain in extremity
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	28 / 170 (16.47%)	47 / 170 (27.65%)	0 / 3 (0.00%)
occurrences all number	45	84	0
Infections and infestations
malaria
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	33 / 170 (19.41%)	33 / 170 (19.41%)	0 / 3 (0.00%)
occurrences all number	62	53	0
nasopharyngitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	15 / 170 (8.82%)	18 / 170 (10.59%)	0 / 3 (0.00%)
occurrences all number	19	34	0
pharyngitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	4 / 170 (2.35%)	10 / 170 (5.88%)	0 / 3 (0.00%)
occurrences all number	4	11	0
rhinitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	11 / 170 (6.47%)	7 / 170 (4.12%)	0 / 3 (0.00%)
occurrences all number	12	10	0
tonsillitis
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	20 / 170 (11.76%)	24 / 170 (14.12%)	0 / 3 (0.00%)
occurrences all number	26	31	0
upper respiratory tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	44 / 170 (25.88%)	37 / 170 (21.76%)	0 / 3 (0.00%)
occurrences all number	76	69	0
urinary tract infection
alternative dictionary used: MedDRA 18.1
subjects affected / exposed	17 / 170 (10.00%)	17 / 170 (10.00%)	0 / 3 (0.00%)
occurrences all number	26	17	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Feb 2013

- Primary endpoint was updated to include a composite of painful crisis or acute chest syndrome and to include not only oral/parenteral opioids and ketorolac but other prescribed analgesics. -Rate of painful crisis added to major secondary efficacy objectives - Hemorrhagic stroke removed from efficacy endpoints. - Inclusion criterion changed to allow patients ≥ 19 kg - Number of participants expected to be enrolled was increased - Stopping rules added for the Data Monitoring Committee - Schedule of events updated to allow additional blood draw

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The pre-defined levels of platelet inhibition and prasugrel as monotherapy may have contributed to the failure to meet any primary/secondary endpoint.

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Clinical trials

Clinical Trial Results: A Phase 3, Double-Blind, Randomized, Efficacy and Safety Comparison of Prasugrel and Placebo in Pediatric Patients with Sickle Cell Disease.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Vaso-Occlusive Crisis (VOC) Events per Participant per Year (Rate of VOC)

Primary: Number of Vaso-Occlusive Crisis (VOC) Events per Participant per Year (Rate of VOC)

Secondary: Monthly Rate of Days with Pain

Secondary: Monthly Rate of Days with Pain

Secondary: Monthly Mean in Faces Pain Scale-Revised Score

Secondary: Monthly Mean in Faces Pain Scale-Revised Score

Secondary: Number of Painful Crisis Events per Participant per Year (Rate of Painful Crisis)

Secondary: Number of Painful Crisis Events per Participant per Year (Rate of Painful Crisis)

Secondary: Number of Hospitalizations for VOC per Participant per Year (Rate of Hospitalizations)

Secondary: Number of Hospitalizations for VOC per Participant per Year (Rate of Hospitalizations)

Secondary: Number of Acute Chest Syndrome per Participant per Year (Rate of Acute Chest Syndrome)

Secondary: Number of Acute Chest Syndrome per Participant per Year (Rate of Acute Chest Syndrome)

Secondary: Number of Red Blood Cell (RBC) Transfusions due to Sickle Cell Disease (SCD) per Participant per Year (Rate of RBC Transfusions)

Secondary: Number of Red Blood Cell (RBC) Transfusions due to Sickle Cell Disease (SCD) per Participant per Year (Rate of RBC Transfusions)

Secondary: Monthly Rate of Days of Analgesic Use

Secondary: Monthly Rate of Days of Analgesic Use

Secondary: Quarterly Rate of School Absence due to Sickle Cell Pain

Secondary: Quarterly Rate of School Absence due to Sickle Cell Pain

Secondary: Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke

Secondary: Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke

Secondary: Number of Days Hospitalized for VOC

Secondary: Number of Days Hospitalized for VOC

Secondary: Time from Randomization to First and Second VOC

Secondary: Time from Randomization to First and Second VOC

Secondary: Percentage of Participants with Hemorrhagic Events Requiring Medical Intervention

Secondary: Percentage of Participants with Hemorrhagic Events Requiring Medical Intervention

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Double-Blind, Randomized, Efficacy and Safety Comparison of Prasugrel and Placebo in Pediatric Patients with Sickle Cell Disease.