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A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease (HESTIA 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02214121
Recruitment Status : Completed
First Posted : August 12, 2014
Results First Posted : May 11, 2018
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease
Interventions Drug: Ticagrelor Dose 1a + Dose 2a
Drug: Ticagrelor Dose 1b + Dose 2b
Enrollment 46
Recruitment Details The study was conducted at 24 centres, in 6 countries. The first patient was enrolled to Part A of the study on 11 Sep 2014, and the last patient completed Part B of the study on 27 Feb 2017. Recruitment was stopped due to protocol amendment between 8 September 2015 and 1 June 2016.
Pre-assignment Details 46 patients were randomised to Part A of the study (open label). Of the patients completing Part A, 25 were randomised to Part B of the study (double blind)
Arm/Group Title Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description Randomised treatment group for Part A of the study. Relevant for the Part A period. Randomised treatment group for Part B of the study. Relevant for the Part B period. Randomised treatment group for Part B of the study. Relevant for the Part B period.
Period Title: Part A
Started 46 0 0
Completed 39 0 0
Not Completed 7 0 0
Reason Not Completed
Patient decision             2             0             0
Dev. of study-specific withdrawal crit.             4             0             0
Other             1             0             0
Period Title: Part B
Started 0 17 8
Completed 0 14 7
Not Completed 0 3 1
Reason Not Completed
Patient decision             0             1             0
Dev. of study-specific withdrawal crit.             0             2             0
Lost to Follow-up             0             0             1
Arm/Group Title Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo Total
Hide Arm/Group Description Actual treatment group for Part A of the study. Relevant for the Part A period. Actual treatment group for Part B of the study. Relevant for the Part B period. Actual treatment group for Part B of the study. Relevant for the Part B period. Total of all reporting groups
Overall Number of Baseline Participants 45 16 7 68
Hide Baseline Analysis Population Description
The baseline characteristics are tabulated by the actual treatment group. This differs from the numbers in the Participant Flow since not all randomised patients received IP and one patient receiving treatment not matching the randomised treatment
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 0 participants 0 participants 45 participants
11.2  (3.34) 11.2  (3.34)
[1]
Measure Description: Relevant for the Part A period of the study.
[2]
Measure Analysis Population Description: Including only part A
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 16 participants 7 participants 23 participants
10.2  (3.73) 9.7  (3.35) 10.0  (3.55)
[1]
Measure Description: Relevant for the Part B period of the study.
[2]
Measure Analysis Population Description: Including only part B
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 0 participants 0 participants 45 participants
Female
24
  53.3%
0 0
24
  53.3%
Male
21
  46.7%
0 0
21
  46.7%
[1]
Measure Description: Relevant for the Part A period of the study
[2]
Measure Analysis Population Description: Including only part A
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 16 participants 7 participants 23 participants
Female 0
9
  56.3%
2
  28.6%
11
  47.8%
Male 0
7
  43.8%
5
  71.4%
12
  52.2%
[1]
Measure Description: Relevant for the Part B period of the study.
[2]
Measure Analysis Population Description: Including only part B
Ethnicity (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 0 participants 0 participants 45 participants
Hispanic or Latino
1
   2.2%
0 0
1
   2.2%
Not Hispanic or Latino
44
  97.8%
0 0
44
  97.8%
Unknown or Not Reported
0
   0.0%
0 0
0
   0.0%
[1]
Measure Description: Relevant for the Part A period
[2]
Measure Analysis Population Description: Including only part A
Ethnicity (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 16 participants 7 participants 23 participants
Hispanic or Latino 0
1
   6.3%
0
   0.0%
1
   4.3%
Not Hispanic or Latino 0
15
  93.8%
7
 100.0%
22
  95.7%
Unknown or Not Reported 0
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Relevant for the Part B period of the study.
[2]
Measure Analysis Population Description: Including only part B
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 45 participants 0 participants 0 participants 45 participants
10
  22.2%
0 0
10
  22.2%
Black or African American Number Analyzed 45 participants 0 participants 0 participants 45 participants
35
  77.8%
0 0
35
  77.8%
Asian Number Analyzed 45 participants 0 participants 0 participants 45 participants
0
   0.0%
0 0
0
   0.0%
Native Hawaiian or Other Pacific Islander Number Analyzed 45 participants 0 participants 0 participants 45 participants
0
   0.0%
0 0
0
   0.0%
American Indian or Alaska Native Number Analyzed 45 participants 0 participants 0 participants 45 participants
0
   0.0%
0 0
0
   0.0%
Other Number Analyzed 45 participants 0 participants 0 participants 45 participants
0
   0.0%
0 0
0
   0.0%
[1]
Measure Description: Relevant for the Part A period of the study
[2]
Measure Analysis Population Description: Including only part A
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
1
   6.3%
0
   0.0%
1
   4.3%
Black or African American Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
15
  93.8%
7
 100.0%
22
  95.7%
Asian Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaska Native Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
Other Number Analyzed 0 participants 16 participants 7 participants 23 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Relevant for the Part B period of the study.
[2]
Measure Analysis Population Description: Including only part B
1.Primary Outcome
Title P2Y12 Reaction Units (PRU) - Part A
Hide Description [Not Specified]
Time Frame PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.
Hide Outcome Measure Data
Hide Analysis Population Description
The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Ticagrelor 0.75 mg/kg Ticagrelor 0.375 mg/kg Ticagrelor 0.563 mg/kg Ticagrelor 1.125 mg/kg Ticagrelor 2.25 mg/kg Ticagrelor 0.125 mg/kg Bid Ticagrelor 0.563 mg/kg Bid Ticagrelor 0.75 mg/kg Bid
Hide Arm/Group Description:
Single dose received at Visit 2.
Single dose received at Visit 2.
Single dose received at Visit 3.
Single dose received at Visit 3
Single dose received at Visit 3.
Single dose received at Visit 3.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Overall Number of Participants Analyzed 14 31 7 18 10 9 14 9 17
Mean (Standard Deviation)
Unit of Measure: P2Y12 reaction units
Pre-dose Number Analyzed 14 participants 30 participants 7 participants 17 participants 10 participants 9 participants 1 participants 9 participants 16 participants
301.6  (46.55) 268.0  (35.95) 295.4  (42.30) 287.7  (34.35) 283.7  (36.88) 277.7  (39.36) 320 [1]   (NA) 205.4  (53.22) 214.7  (48.71)
2 hours post-dose Number Analyzed 14 participants 31 participants 7 participants 18 participants 10 participants 9 participants 13 participants 9 participants 17 participants
278.2  (47.20) 138.4  (70.68) 229.0  (64.22) 176.2  (79.53) 128.9  (37.68) 79.9  (47.74) 271.2  (70.35) 102.0  (72.53) 152.0  (72.35)
6 hours post-dose Number Analyzed 5 participants 28 participants 2 participants 14 participants 9 participants 9 participants 0 participants 0 participants 0 participants
276.0  (75.43) 189.0  (69.84) 266.0  (57.98) 190.4  (47.78) 191.2  (57.59) 141.7  (69.58)
8 hours post-dose Number Analyzed 5 participants 0 participants 3 participants 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants
343.0  (38.13) 318.3  (66.43) 318.0 [1]   (NA)
[1]
Mean based on one observation.
2.Primary Outcome
Title P2Y12 Reaction Units (PRU) - Part B
Hide Description [Not Specified]
Time Frame PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid Placebo
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9 3
Mean (Standard Deviation)
Unit of Measure: P2Y12 reaction units
Pre-dose Number Analyzed 8 participants 3 participants
282.8  (19.26) 313.3  (20.13)
2 hours post-dose Number Analyzed 9 participants 3 participants
259.6  (61.95) 217.3  (78.34)
3.Primary Outcome
Title Maximum Plasma Concentration (Cmax) - Part A
Hide Description [Not Specified]
Time Frame PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Ticagrelor 0.75 mg/kg Ticagrelor 0.375 mg/kg Ticagrelor 0.563 mg/kg Ticagrelor 1.125 mg/kg Ticagrelor 2.25 mg/kg Ticagrelor 0.125 mg/kg Bid Ticagrelor 0.563 mg/kg Bid Ticagrelor 0.75 mg/kg Bid
Hide Arm/Group Description:
Single dose received at Visit 2.
Single dose received at Visit 2.
Single dose received at Visit 3.
Single dose received at Visit 3
Single dose received at Visit 3.
Single dose received at Visit 3.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Overall Number of Participants Analyzed 14 31 7 18 10 9 14 9 17
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
15.240  (15.2709) 162.961  (84.9230) 52.069  (34.4115) 96.031  (51.4902) 269.174  (162.2147) 566.550  (225.9447) 13.973  (15.3652) 111.367  (81.1597) 157.216  (114.8138)
4.Primary Outcome
Title Maximum Plasma Concentration (Cmax) - Part B
Hide Description [Not Specified]
Time Frame PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
16.394  (13.3671)
5.Primary Outcome
Title Area Under the Plasma Concentration Time Curve (AUC) - Part A
Hide Description The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Ticagrelor 0.75 mg/kg Ticagrelor 0.375 mg/kg Ticagrelor 0.563 mg/kg Ticagrelor 1.125 mg/kg Ticagrelor 2.25 mg/kg Ticagrelor 0.125 mg/kg Bid Ticagrelor 0.563 mg/kg Bid Ticagrelor 0.75 mg/kg Bid
Hide Arm/Group Description:
Single dose received at Visit 2.
Single dose received at Visit 2.
Single dose received at Visit 3.
Single dose received at Visit 3
Single dose received at Visit 3.
Single dose received at Visit 3.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Overall Number of Participants Analyzed 14 31 7 18 10 9 14 9 17
Geometric Mean (Standard Deviation)
Unit of Measure: ng*h/mL
161.9  (72.24) 1151.9  (308.39) 437.5  (262.24) 879.3  (236.12) 1638.7  (521.80) 2850.9  (1277.39) 161.9  (72.24) 913.5  (208.82) 1022.4  (287.32)
6.Primary Outcome
Title Area Under the Plasma Concentration Time Curve (AUC) - Part B
Hide Description The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9
Geometric Mean (Standard Deviation)
Unit of Measure: ng*h/mL
160.6  (88.58)
7.Secondary Outcome
Title Assessment of Ticagrelor Concentration - Part A
Hide Description [Not Specified]
Time Frame In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Ticagrelor 0.75 mg/kg Ticagrelor 0.375 mg/kg Ticagrelor 0.563 mg/kg Ticagrelor 1.125 mg/kg Ticagrelor 2.25 mg/kg Ticagrelor 0.125 mg/kg Bid Ticagrelor 0.563 mg/kg Bid Ticagrelor 0.75 mg/kg Bid
Hide Arm/Group Description:
Single dose received at Visit 2.
Single dose received at Visit 2.
Single dose received at Visit 3.
Single dose received at Visit 3
Single dose received at Visit 3.
Single dose received at Visit 3.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Overall Number of Participants Analyzed 14 31 7 18 10 9 14 9 17
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 9 participants 16 participants
2.170 [1]   (NA) 31.937  (48.6501) 28.066  (27.1344)
1 hour post-dose Number Analyzed 14 participants 31 participants 7 participants 18 participants 10 participants 9 participants 0 participants 8 participants 17 participants
12.713  (16.0627) 104.243  (103.1502) 34.069  (42.3746) 33.294  (55.4258) 182.558  (188.4254) 390.568  (294.2189) 80.414  (75.9675) 151.520  (116.0079)
2 hours post-dose Number Analyzed 14 participants 31 participants 7 participants 18 participants 10 participants 9 participants 14 participants 9 participants 16 participants
11.465  (8.7427) 107.729  (62.8343) 37.782  (31.6890) 74.626  (50.7053) 162.435  (161.8489) 426.804  (212.5385) 13.973  (15.3652) 102.166  (78.0785) 101.618  (65.2415)
4 hours post-dose Number Analyzed 14 participants 31 participants 6 participants 18 participants 10 participants 9 participants 0 participants 0 participants 0 participants
6.647  (4.4533) 75.907  (31.2786) 20.122  (9.9383) 51.005  (24.6435) 118.217  (42.0873) 188.383  (111.9267)
6 hours post-dose Number Analyzed 7 participants 31 participants 3 participants 16 participants 10 participants 9 participants 0 participants 0 participants 0 participants
3.663  (3.4061) 52.966  (29.0297) 19.435  (15.7259) 45.502  (17.8950) 69.708  (44.3168) 125.279  (89.0005)
8 hours post-dose Number Analyzed 6 participants 0 participants 3 participants 2 participants 0 participants 0 participants 0 participants 0 participants 0 participants
3.880  (3.3171) 15.699  (20.7596) 15.691  (15.1392)
[1]
Mean based on one observation.
8.Secondary Outcome
Title Assessment of Ticagrelor Concentration - Part B
Hide Description [Not Specified]
Time Frame PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 8 participants
2.478  (3.9580)
1 hour post-dose Number Analyzed 7 participants
9.677  (9.4275)
2 hours post-dose Number Analyzed 9 participants
14.144  (12.4711)
4 hours post-dose Number Analyzed 8 participants
9.605  (14.4979)
9.Secondary Outcome
Title Assessment of AR-C124910XX Concentration - Part A
Hide Description AR-C124910XX is the active metabolite of Ticagrelor
Time Frame In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Ticagrelor 0.75 mg/kg Ticagrelor 0.375 mg/kg Ticagrelor 0.563 mg/kg Ticagrelor 1.125 mg/kg Ticagrelor 2.25 mg/kg Ticagrelor 0.125 mg/kg Bid Ticagrelor 0.563 mg/kg Bid Ticagrelor 0.75 mg/kg Bid
Hide Arm/Group Description:
Single dose received at Visit 2.
Single dose received at Visit 2.
Single dose received at Visit 3.
Single dose received at Visit 3
Single dose received at Visit 3.
Single dose received at Visit 3.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Repeated bid treatment between Visit 3 and Visit 4.
Overall Number of Participants Analyzed 14 31 7 18 10 9 14 9 17
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 9 participants 16 participants
1.250 [1]   (NA) 17.380  (10.0399) 20.359  (15.0788)
1 hour post-dose Number Analyzed 14 participants 31 participants 7 participants 18 participants 10 participants 9 participants 0 participants 8 participants 17 participants
1.782  (1.6604) 16.302  (22.4614) 4.577  (7.8610) 3.708  (13.3332) 30.070  (44.2950) 63.088  (84.2091) 24.945  (15.6547) 43.986  (29.8127)
2 hours post-dose Number Analyzed 14 participants 31 participants 7 participants 18 participants 10 participants 9 participants 14 participants 9 participants 16 participants
2.681  (2.0733) 33.256  (25.3854) 11.757  (13.3322) 15.918  (17.4849) 52.932  (69.1056) 149.772  (71.3624) 4.026  (4.7624) 37.013  (32.7650) 44.690  (31.6577)
4 hours post-dose Number Analyzed 14 participants 31 participants 6 participants 18 participants 10 participants 9 participants 0 participants 0 participants 0 participants
2.071  (1.2770) 29.860  (13.8726) 7.630  (6.3730) 17.015  (7.9272) 50.887  (25.6964) 101.370  (44.6207)
6 hours post-dose Number Analyzed 7 participants 31 participants 3 participants 16 participants 10 participants 9 participants 0 participants 0 participants 0 participants
1.646  (1.0427) 25.276  (10.8318) 9.762  (2.3304) 16.703  (5.8115) 35.716  (22.3351) 76.941  (39.9167)
8 hours post-dose Number Analyzed 6 participants 0 participants 3 participants 2 participants 0 participants 0 participants 0 participants 0 participants 0 participants
1.715  (1.0226) 6.176  (6.3168) 9.232  (2.5385)
[1]
Mean based on one observation.
10.Secondary Outcome
Title Assessment of AR-C124910XX Concentration - Part B
Hide Description AR-C124910XX is the active metabolite of Ticagrelor
Time Frame PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose Number Analyzed 8 participants
1.810  (1.1213)
1 hour post-dose Number Analyzed 7 participants
2.865  (1.6443)
2 hours post-dose Number Analyzed 9 participants
4.160  (3.1503)
4 hours post-dose Number Analyzed 8 participants
3.953  (4.1179)
11.Secondary Outcome
Title Oral Clearance (CL/F) - Part A
Hide Description The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Overall
Hide Arm/Group Description:
All patients receiving Ticagrelor during Part A.
Overall Number of Participants Analyzed 45
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
22.50  (7.531)
12.Secondary Outcome
Title Oral Clearance (CL/F) - Part B
Hide Description The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
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Hide Analysis Population Description
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Ticagrelor 0.125 mg/kg Bid
Hide Arm/Group Description:
Repeated bid treatment during Part B.
Overall Number of Participants Analyzed 9
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
19.15  (6.673)
13.Secondary Outcome
Title Number of Vaso-occlusive Crises - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
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Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
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Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 15 8
Mean (Standard Deviation)
Unit of Measure: Number of events
1.0  (2.00) 0.6  (0.74)
14.Secondary Outcome
Title Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
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Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 15 8
Mean (Standard Deviation)
Unit of Measure: Number of events
0.2  (0.41) 0.1  (0.35)
15.Secondary Outcome
Title Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
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Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 15 8
Mean (Standard Deviation)
Unit of Measure: Percentage of days
4.52  (11.816) 1.34  (3.788)
16.Secondary Outcome
Title Percentage of Days With Pain (Age >=4) - Part B
Hide Description Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
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Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
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Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 14 8
Mean (Standard Deviation)
Unit of Measure: Percentage of days
27.01  (34.065) 31.78  (23.731)
17.Secondary Outcome
Title Mean Intensity of Pain (Age >=4) - Part B
Hide Description Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 14 8
Mean (Standard Deviation)
Unit of Measure: Mean score on scale
Overall - Part B Number Analyzed 14 participants 8 participants
1.40  (2.027) 0.87  (0.493)
1st week Number Analyzed 13 participants 8 participants
1.64  (2.603) 1.36  (0.827)
2nd week Number Analyzed 13 participants 7 participants
1.11  (2.236) 0.38  (0.525)
3rd week Number Analyzed 12 participants 6 participants
1.06  (1.881) 0.67  (1.116)
4th week Number Analyzed 12 participants 6 participants
1.46  (2.624) 0.83  (0.901)
18.Secondary Outcome
Title Percentage of Days of Analgesic Use (Age >= 4) - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 14 8
Mean (Standard Deviation)
Unit of Measure: Percentage of days
16.79  (20.838) 18.56  (19.110)
19.Secondary Outcome
Title Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 14 8
Mean (Standard Deviation)
Unit of Measure: Percentage of days
12.46  (22.502) 0.54  (1.537)
20.Secondary Outcome
Title Percentage of Days of Absence From School or Work (Age >=6) - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 11 6
Mean (Standard Deviation)
Unit of Measure: Percentage of days
4.87  (10.865) 5.95  (9.494)
21.Other Pre-specified Outcome
Title Haemorrhagic Events - Part A
Hide Description [Not Specified]
Time Frame From randomisation to Part A (week 0) through Visit 4 (week 2)
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Hide Analysis Population Description
All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.
Arm/Group Title Part A - Ticagrelor
Hide Arm/Group Description:
Randomised treatment group for Part A of the study. Relevant for the Part A period.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: Number of events
0
22.Other Pre-specified Outcome
Title Haemorrhagic Events - Part B
Hide Description [Not Specified]
Time Frame During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received. Erroneously treated patients will be accounted for in the actual treatment group.
Arm/Group Title Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description:
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Randomised treatment group for Part B of the study. Relevant for the Part B period.
Overall Number of Participants Analyzed 16 7
Measure Type: Number
Unit of Measure: Number of events
0 0
Time Frame SAEs were collected from Visit 1 and AEs from Visit 2. SAEs and Other AEs are presented by study period, where Part A consists of the time from randomization to Part A through Visit 4. Part B starts the day after Visit 4 and continues until Visit 8.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo
Hide Arm/Group Description Randomised treatment group for Part A of the study. Relevant for the Part A period. Randomised treatment group for Part B of the study. Relevant for the Part B period. Randomised treatment group for Part B of the study. Relevant for the Part B period.
All-Cause Mortality
Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/45 (0.00%)      0/16 (0.00%)      0/7 (0.00%)    
Hide Serious Adverse Events
Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/45 (11.11%)      4/16 (25.00%)      1/7 (14.29%)    
Blood and lymphatic system disorders       
Sickle cell anemia with crisis  1  3/45 (6.67%)  3 3/16 (18.75%)  3 1/7 (14.29%)  1
Infections and infestations       
Gastroenteritis viral  1  1/45 (2.22%)  1 0/16 (0.00%)  0 0/7 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute chest syndrome  1  1/45 (2.22%)  1 1/16 (6.25%)  1 0/7 (0.00%)  0
1
Term from vocabulary, MedDRA version 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A - Ticagrelor Part B - Ticagrelor Part B - Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/45 (48.89%)      12/16 (75.00%)      5/7 (71.43%)    
Blood and lymphatic system disorders       
Sickle cell anemia with crisis  1  6/45 (13.33%)  8 1/16 (6.25%)  1 1/7 (14.29%)  1
Ear and labyrinth disorders       
Tympanic membrane perforation  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  6/45 (13.33%)  6 3/16 (18.75%)  6 2/7 (28.57%)  2
Abdominal pain upper  1  0/45 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Gastritis  1  0/45 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Nausea  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Vomiting  1  0/45 (0.00%)  0 3/16 (18.75%)  3 0/7 (0.00%)  0
General disorders       
Chest discomfort  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Facial pain  1  2/45 (4.44%)  4 1/16 (6.25%)  1 1/7 (14.29%)  2
Non-cardiac chest pain  1  2/45 (4.44%)  2 1/16 (6.25%)  2 1/7 (14.29%)  1
Pain  1  0/45 (0.00%)  0 1/16 (6.25%)  2 0/7 (0.00%)  0
Pyrexia  1  1/45 (2.22%)  1 2/16 (12.50%)  2 0/7 (0.00%)  0
Infections and infestations       
Conjunctivitis  1  0/45 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Nasopharyngitis  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Otitis media  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Pharyngitis  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Tinea infection  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  5/45 (11.11%)  7 4/16 (25.00%)  4 2/7 (28.57%)  2
Back pain  1  3/45 (6.67%)  3 2/16 (12.50%)  2 1/7 (14.29%)  3
Musculoskeletal pain  1  1/45 (2.22%)  1 2/16 (12.50%)  2 1/7 (14.29%)  1
Neck pain  1  0/45 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Pain in extremity  1  5/45 (11.11%)  8 3/16 (18.75%)  4 2/7 (28.57%)  2
Nervous system disorders       
Dizziness  1  1/45 (2.22%)  1 1/16 (6.25%)  1 0/7 (0.00%)  0
Headache  1  4/45 (8.89%)  7 0/16 (0.00%)  0 2/7 (28.57%)  2
Reproductive system and breast disorders       
Pelvic pain  1  0/45 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/45 (2.22%)  1 2/16 (12.50%)  2 0/7 (0.00%)  0
Oropharyngeal pain  1  1/45 (2.22%)  1 3/16 (18.75%)  3 0/7 (0.00%)  0
1
Term from vocabulary, MedDRA version 19.1
Indicates events were collected by systematic assessment
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.
No publication can be made in advance of the first multicenter publication by the sponsor. Any publication will be submitted to the sponsor for review prior to the being published. The sponsor has the right to defer this publication for a period between 60 days to 6 months. The sponsor has the right to restrict the use of confidential information in any of the publications submitted.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Brilinta Global Clinical Lead
Organization: AstraZeneca
Phone: +46 31 776 1000
EMail: kontakt@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02214121    
Other Study ID Numbers: D5136C00007
2014-001006-18 ( EudraCT Number )
First Submitted: August 8, 2014
First Posted: August 12, 2014
Results First Submitted: February 5, 2018
Results First Posted: May 11, 2018
Last Update Posted: December 14, 2018