Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease
Conditions
Keywords
sickle cell anemia, paediatric
Brief summary
The purpose of this Phase II dose-ranging study is to investigate pharmacokinetic (PK) and pharmacodynamic (PD) properties of various doses of ticagrelor followed by 4 weeks of twice-daily treatment in paediatric patients with sickle cell disease
Detailed description
This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double blind, placebo-controlled extension phase in paediatric patients with sickle cell disease (SCD). Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and pharmacodynamic (PD) measurements will be determined following each dose. Platelet aggregation will be measured using the VerifyNow™ P2Y12 assay. Following these 2 single doses, all patients will receive open-label one-week treatment with ticagrelor twice daily to determine tolerability prior to randomisation into Part B. Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or placebo for a 4-week treatment phase. During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC) and for other disease manifestations such as daily pain, analgesic use and complications of SCD.
Interventions
DRUGTicagrelor Dose 1a + Dose 2a
Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
DRUGTicagrelor Dose 1b + Dose 2b
Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children aged ≥2 to \<18 years of age * Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)
Exclusion criteria
* At risk for haemorrhagic or bradycardic events * Significant hepatic impairment * Renal failure requiring dialysis * Concomitant oral or intravenous therapy with strong CYP3A4 (cytochrome) inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers. * Surgical procedure planned to occur during the study. * Patients who are currently pregnant or breastfeeding or planning to become pregnant during the study. * Patients who have known hypersensitivity or contraindication to ticagrelor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. |
| Area Under the Plasma Concentration Time Curve (AUC) - Part A | 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). | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. |
| P2Y12 Reaction Units (PRU) - Part A | 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. | — |
| P2Y12 Reaction Units (PRU) - Part B | PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B. | — |
| Maximum Plasma Concentration (Cmax) - Part A | 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). | — |
| Maximum Plasma Concentration (Cmax) - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oral Clearance (CL/F) - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. |
| Number of Vaso-occlusive Crises - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Mean Intensity of Pain (Age >=4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain |
| Percentage of Days of Analgesic Use (Age >= 4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Percentage of Days of Absence From School or Work (Age >=6) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | — |
| Percentage of Days With Pain (Age >=4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain |
| Assessment of Ticagrelor Concentration - Part A | 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) | — |
| Assessment of Ticagrelor Concentration - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | — |
| Assessment of AR-C124910XX Concentration - Part A | 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) | AR-C124910XX is the active metabolite of Ticagrelor |
| Assessment of AR-C124910XX Concentration - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | AR-C124910XX is the active metabolite of Ticagrelor |
| Oral Clearance (CL/F) - Part A | 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). | The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis. |
Other
| Measure | Time frame |
|---|---|
| Haemorrhagic Events - Part A | From randomisation to Part A (week 0) through Visit 4 (week 2) |
| Haemorrhagic Events - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). |
Countries
Canada, Kenya, Lebanon, South Africa, United Kingdom, United States
Participant flow
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)
Participants by arm
| Arm | Count |
|---|---|
| Part A - Ticagrelor Actual treatment group for Part A of the study. Relevant for the Part A period. | 45 |
| Part B - Ticagrelor Actual treatment group for Part B of the study. Relevant for the Part B period. | 16 |
| Part B - Placebo Actual treatment group for Part B of the study. Relevant for the Part B period. | 7 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A | Dev. of study-specific withdrawal crit. | 4 | 0 | 0 |
| Part A | Other | 1 | 0 | 0 |
| Part A | Patient decision | 2 | 0 | 0 |
| Part B | Dev. of study-specific withdrawal crit. | 0 | 2 | 0 |
| Part B | Lost to Follow-up | 0 | 0 | 1 |
| Part B | Patient decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A - Ticagrelor | Total | Part B - Ticagrelor | Part B - Placebo |
|---|---|---|---|---|
| Age, Continuous | 11.2 Years STANDARD_DEVIATION 3.34 | 10.0 Years STANDARD_DEVIATION 3.55 | 10.2 Years STANDARD_DEVIATION 3.73 | 9.7 Years STANDARD_DEVIATION 3.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 44 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 35 Participants | 15 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 10 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 24 Participants | 9 Participants | 2 Participants |
| Sex: Female, Male Male | 21 Participants | 12 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 16 | 0 / 7 |
| other Total, other adverse events | 22 / 45 | 12 / 16 | 5 / 7 |
| serious Total, serious adverse events | 5 / 45 | 4 / 16 | 1 / 7 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve (AUC) - Part A
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 161.9 ng*h/mL | Standard Deviation 72.24 |
| Ticagrelor 0.75 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 1151.9 ng*h/mL | Standard Deviation 308.39 |
| Ticagrelor 0.375 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 437.5 ng*h/mL | Standard Deviation 262.24 |
| Ticagrelor 0.563 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 879.3 ng*h/mL | Standard Deviation 236.12 |
| Ticagrelor 1.125 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 1638.7 ng*h/mL | Standard Deviation 521.8 |
| Ticagrelor 2.25 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 2850.9 ng*h/mL | Standard Deviation 1277.39 |
| Ticagrelor 0.125 mg/kg Bid | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 161.9 ng*h/mL | Standard Deviation 72.24 |
| Ticagrelor 0.563 mg/kg Bid | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 913.5 ng*h/mL | Standard Deviation 208.82 |
| Ticagrelor 0.75 mg/kg Bid | Area Under the Plasma Concentration Time Curve (AUC) - Part A | 1022.4 ng*h/mL | Standard Deviation 287.32 |
Primary
Area Under the Plasma Concentration Time Curve (AUC) - Part B
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Area Under the Plasma Concentration Time Curve (AUC) - Part B | 160.6 ng*h/mL | Standard Deviation 88.58 |
Primary
Maximum Plasma Concentration (Cmax) - Part A
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 15.240 ng/mL | Standard Deviation 15.2709 |
| Ticagrelor 0.75 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 162.961 ng/mL | Standard Deviation 84.923 |
| Ticagrelor 0.375 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 52.069 ng/mL | Standard Deviation 34.4115 |
| Ticagrelor 0.563 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 96.031 ng/mL | Standard Deviation 51.4902 |
| Ticagrelor 1.125 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 269.174 ng/mL | Standard Deviation 162.2147 |
| Ticagrelor 2.25 mg/kg | Maximum Plasma Concentration (Cmax) - Part A | 566.550 ng/mL | Standard Deviation 225.9447 |
| Ticagrelor 0.125 mg/kg Bid | Maximum Plasma Concentration (Cmax) - Part A | 13.973 ng/mL | Standard Deviation 15.3652 |
| Ticagrelor 0.563 mg/kg Bid | Maximum Plasma Concentration (Cmax) - Part A | 111.367 ng/mL | Standard Deviation 81.1597 |
| Ticagrelor 0.75 mg/kg Bid | Maximum Plasma Concentration (Cmax) - Part A | 157.216 ng/mL | Standard Deviation 114.8138 |
Primary
Maximum Plasma Concentration (Cmax) - Part B
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Maximum Plasma Concentration (Cmax) - Part B | 16.394 ng/mL | Standard Deviation 13.3671 |
Primary
P2Y12 Reaction Units (PRU) - Part A
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 301.6 P2Y12 reaction units | Standard Deviation 46.55 |
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 276.0 P2Y12 reaction units | Standard Deviation 75.43 |
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 8 hours post-dose | 343.0 P2Y12 reaction units | Standard Deviation 38.13 |
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 278.2 P2Y12 reaction units | Standard Deviation 47.2 |
| Ticagrelor 0.75 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 138.4 P2Y12 reaction units | Standard Deviation 70.68 |
| Ticagrelor 0.75 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 189.0 P2Y12 reaction units | Standard Deviation 69.84 |
| Ticagrelor 0.75 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 268.0 P2Y12 reaction units | Standard Deviation 35.95 |
| Ticagrelor 0.375 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 8 hours post-dose | 318.3 P2Y12 reaction units | Standard Deviation 66.43 |
| Ticagrelor 0.375 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 295.4 P2Y12 reaction units | Standard Deviation 42.3 |
| Ticagrelor 0.375 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 229.0 P2Y12 reaction units | Standard Deviation 64.22 |
| Ticagrelor 0.375 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 266.0 P2Y12 reaction units | Standard Deviation 57.98 |
| Ticagrelor 0.563 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 8 hours post-dose | 318.0 P2Y12 reaction units | — |
| Ticagrelor 0.563 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 287.7 P2Y12 reaction units | Standard Deviation 34.35 |
| Ticagrelor 0.563 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 176.2 P2Y12 reaction units | Standard Deviation 79.53 |
| Ticagrelor 0.563 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 190.4 P2Y12 reaction units | Standard Deviation 47.78 |
| Ticagrelor 1.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 128.9 P2Y12 reaction units | Standard Deviation 37.68 |
| Ticagrelor 1.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 191.2 P2Y12 reaction units | Standard Deviation 57.59 |
| Ticagrelor 1.125 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 283.7 P2Y12 reaction units | Standard Deviation 36.88 |
| Ticagrelor 2.25 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 79.9 P2Y12 reaction units | Standard Deviation 47.74 |
| Ticagrelor 2.25 mg/kg | P2Y12 Reaction Units (PRU) - Part A | 6 hours post-dose | 141.7 P2Y12 reaction units | Standard Deviation 69.58 |
| Ticagrelor 2.25 mg/kg | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 277.7 P2Y12 reaction units | Standard Deviation 39.36 |
| Ticagrelor 0.125 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 271.2 P2Y12 reaction units | Standard Deviation 70.35 |
| Ticagrelor 0.125 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 320 P2Y12 reaction units | — |
| Ticagrelor 0.563 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 102.0 P2Y12 reaction units | Standard Deviation 72.53 |
| Ticagrelor 0.563 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 205.4 P2Y12 reaction units | Standard Deviation 53.22 |
| Ticagrelor 0.75 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | 2 hours post-dose | 152.0 P2Y12 reaction units | Standard Deviation 72.35 |
| Ticagrelor 0.75 mg/kg Bid | P2Y12 Reaction Units (PRU) - Part A | Pre-dose | 214.7 P2Y12 reaction units | Standard Deviation 48.71 |
Primary
P2Y12 Reaction Units (PRU) - Part B
Time frame: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part B | Pre-dose | 282.8 P2Y12 reaction units | Standard Deviation 19.26 |
| Ticagrelor 0.125 mg/kg | P2Y12 Reaction Units (PRU) - Part B | 2 hours post-dose | 259.6 P2Y12 reaction units | Standard Deviation 61.95 |
| Ticagrelor 0.75 mg/kg | P2Y12 Reaction Units (PRU) - Part B | Pre-dose | 313.3 P2Y12 reaction units | Standard Deviation 20.13 |
| Ticagrelor 0.75 mg/kg | P2Y12 Reaction Units (PRU) - Part B | 2 hours post-dose | 217.3 P2Y12 reaction units | Standard Deviation 78.34 |
Secondary
Assessment of AR-C124910XX Concentration - Part A
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 2.681 ng/mL | Standard Deviation 2.0733 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 8 hours post-dose | 1.715 ng/mL | Standard Deviation 1.0226 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 2.071 ng/mL | Standard Deviation 1.277 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 1.782 ng/mL | Standard Deviation 1.6604 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 1.646 ng/mL | Standard Deviation 1.0427 |
| Ticagrelor 0.75 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 25.276 ng/mL | Standard Deviation 10.8318 |
| Ticagrelor 0.75 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 16.302 ng/mL | Standard Deviation 22.4614 |
| Ticagrelor 0.75 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 33.256 ng/mL | Standard Deviation 25.3854 |
| Ticagrelor 0.75 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 29.860 ng/mL | Standard Deviation 13.8726 |
| Ticagrelor 0.375 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 8 hours post-dose | 6.176 ng/mL | Standard Deviation 6.3168 |
| Ticagrelor 0.375 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 4.577 ng/mL | Standard Deviation 7.861 |
| Ticagrelor 0.375 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 9.762 ng/mL | Standard Deviation 2.3304 |
| Ticagrelor 0.375 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 7.630 ng/mL | Standard Deviation 6.373 |
| Ticagrelor 0.375 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 11.757 ng/mL | Standard Deviation 13.3322 |
| Ticagrelor 0.563 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 3.708 ng/mL | Standard Deviation 13.3332 |
| Ticagrelor 0.563 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 15.918 ng/mL | Standard Deviation 17.4849 |
| Ticagrelor 0.563 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 17.015 ng/mL | Standard Deviation 7.9272 |
| Ticagrelor 0.563 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 8 hours post-dose | 9.232 ng/mL | Standard Deviation 2.5385 |
| Ticagrelor 0.563 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 16.703 ng/mL | Standard Deviation 5.8115 |
| Ticagrelor 1.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 35.716 ng/mL | Standard Deviation 22.3351 |
| Ticagrelor 1.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 52.932 ng/mL | Standard Deviation 69.1056 |
| Ticagrelor 1.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 50.887 ng/mL | Standard Deviation 25.6964 |
| Ticagrelor 1.125 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 30.070 ng/mL | Standard Deviation 44.295 |
| Ticagrelor 2.25 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 6 hours post-dose | 76.941 ng/mL | Standard Deviation 39.9167 |
| Ticagrelor 2.25 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 63.088 ng/mL | Standard Deviation 84.2091 |
| Ticagrelor 2.25 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 149.772 ng/mL | Standard Deviation 71.3624 |
| Ticagrelor 2.25 mg/kg | Assessment of AR-C124910XX Concentration - Part A | 4 hours post-dose | 101.370 ng/mL | Standard Deviation 44.6207 |
| Ticagrelor 0.125 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 4.026 ng/mL | Standard Deviation 4.7624 |
| Ticagrelor 0.125 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | Pre-dose | 1.250 ng/mL | — |
| Ticagrelor 0.563 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 37.013 ng/mL | Standard Deviation 32.765 |
| Ticagrelor 0.563 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 24.945 ng/mL | Standard Deviation 15.6547 |
| Ticagrelor 0.563 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | Pre-dose | 17.380 ng/mL | Standard Deviation 10.0399 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | 2 hours post-dose | 44.690 ng/mL | Standard Deviation 31.6577 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | 1 hour post-dose | 43.986 ng/mL | Standard Deviation 29.8127 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of AR-C124910XX Concentration - Part A | Pre-dose | 20.359 ng/mL | Standard Deviation 15.0788 |
Secondary
Assessment of AR-C124910XX Concentration - Part B
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part B | Pre-dose | 1.810 ng/mL | Standard Deviation 1.1213 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part B | 1 hour post-dose | 2.865 ng/mL | Standard Deviation 1.6443 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part B | 2 hours post-dose | 4.160 ng/mL | Standard Deviation 3.1503 |
| Ticagrelor 0.125 mg/kg | Assessment of AR-C124910XX Concentration - Part B | 4 hours post-dose | 3.953 ng/mL | Standard Deviation 4.1179 |
Secondary
Assessment of Ticagrelor Concentration - Part A
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 11.465 ng/mL | Standard Deviation 8.7427 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 8 hours post-dose | 3.880 ng/mL | Standard Deviation 3.3171 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 6.647 ng/mL | Standard Deviation 4.4533 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 12.713 ng/mL | Standard Deviation 16.0627 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 3.663 ng/mL | Standard Deviation 3.4061 |
| Ticagrelor 0.75 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 52.966 ng/mL | Standard Deviation 29.0297 |
| Ticagrelor 0.75 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 104.243 ng/mL | Standard Deviation 103.1502 |
| Ticagrelor 0.75 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 107.729 ng/mL | Standard Deviation 62.8343 |
| Ticagrelor 0.75 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 75.907 ng/mL | Standard Deviation 31.2786 |
| Ticagrelor 0.375 mg/kg | Assessment of Ticagrelor Concentration - Part A | 8 hours post-dose | 15.699 ng/mL | Standard Deviation 20.7596 |
| Ticagrelor 0.375 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 34.069 ng/mL | Standard Deviation 42.3746 |
| Ticagrelor 0.375 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 19.435 ng/mL | Standard Deviation 15.7259 |
| Ticagrelor 0.375 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 20.122 ng/mL | Standard Deviation 9.9383 |
| Ticagrelor 0.375 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 37.782 ng/mL | Standard Deviation 31.689 |
| Ticagrelor 0.563 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 33.294 ng/mL | Standard Deviation 55.4258 |
| Ticagrelor 0.563 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 74.626 ng/mL | Standard Deviation 50.7053 |
| Ticagrelor 0.563 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 51.005 ng/mL | Standard Deviation 24.6435 |
| Ticagrelor 0.563 mg/kg | Assessment of Ticagrelor Concentration - Part A | 8 hours post-dose | 15.691 ng/mL | Standard Deviation 15.1392 |
| Ticagrelor 0.563 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 45.502 ng/mL | Standard Deviation 17.895 |
| Ticagrelor 1.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 69.708 ng/mL | Standard Deviation 44.3168 |
| Ticagrelor 1.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 162.435 ng/mL | Standard Deviation 161.8489 |
| Ticagrelor 1.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 118.217 ng/mL | Standard Deviation 42.0873 |
| Ticagrelor 1.125 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 182.558 ng/mL | Standard Deviation 188.4254 |
| Ticagrelor 2.25 mg/kg | Assessment of Ticagrelor Concentration - Part A | 6 hours post-dose | 125.279 ng/mL | Standard Deviation 89.0005 |
| Ticagrelor 2.25 mg/kg | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 390.568 ng/mL | Standard Deviation 294.2189 |
| Ticagrelor 2.25 mg/kg | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 426.804 ng/mL | Standard Deviation 212.5385 |
| Ticagrelor 2.25 mg/kg | Assessment of Ticagrelor Concentration - Part A | 4 hours post-dose | 188.383 ng/mL | Standard Deviation 111.9267 |
| Ticagrelor 0.125 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 13.973 ng/mL | Standard Deviation 15.3652 |
| Ticagrelor 0.125 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | Pre-dose | 2.170 ng/mL | — |
| Ticagrelor 0.563 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 102.166 ng/mL | Standard Deviation 78.0785 |
| Ticagrelor 0.563 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 80.414 ng/mL | Standard Deviation 75.9675 |
| Ticagrelor 0.563 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | Pre-dose | 31.937 ng/mL | Standard Deviation 48.6501 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | 2 hours post-dose | 101.618 ng/mL | Standard Deviation 65.2415 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | 1 hour post-dose | 151.520 ng/mL | Standard Deviation 116.0079 |
| Ticagrelor 0.75 mg/kg Bid | Assessment of Ticagrelor Concentration - Part A | Pre-dose | 28.066 ng/mL | Standard Deviation 27.1344 |
Secondary
Assessment of Ticagrelor Concentration - Part B
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part B | Pre-dose | 2.478 ng/mL | Standard Deviation 3.958 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part B | 1 hour post-dose | 9.677 ng/mL | Standard Deviation 9.4275 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part B | 2 hours post-dose | 14.144 ng/mL | Standard Deviation 12.4711 |
| Ticagrelor 0.125 mg/kg | Assessment of Ticagrelor Concentration - Part B | 4 hours post-dose | 9.605 ng/mL | Standard Deviation 14.4979 |
Secondary
Mean Intensity of Pain (Age >=4) - Part B
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).
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 1st week | 1.64 Mean score on scale | Standard Deviation 2.603 |
| Ticagrelor 0.125 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 3rd week | 1.06 Mean score on scale | Standard Deviation 1.881 |
| Ticagrelor 0.125 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 2nd week | 1.11 Mean score on scale | Standard Deviation 2.236 |
| Ticagrelor 0.125 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 4th week | 1.46 Mean score on scale | Standard Deviation 2.624 |
| Ticagrelor 0.125 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | Overall - Part B | 1.40 Mean score on scale | Standard Deviation 2.027 |
| Ticagrelor 0.75 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 4th week | 0.83 Mean score on scale | Standard Deviation 0.901 |
| Ticagrelor 0.75 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | Overall - Part B | 0.87 Mean score on scale | Standard Deviation 0.493 |
| Ticagrelor 0.75 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 1st week | 1.36 Mean score on scale | Standard Deviation 0.827 |
| Ticagrelor 0.75 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 2nd week | 0.38 Mean score on scale | Standard Deviation 0.525 |
| Ticagrelor 0.75 mg/kg | Mean Intensity of Pain (Age >=4) - Part B | 3rd week | 0.67 Mean score on scale | Standard Deviation 1.116 |
Secondary
Number of Vaso-occlusive Crises - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Number of Vaso-occlusive Crises - Part B | 1.0 Number of events | Standard Deviation 2 |
| Ticagrelor 0.75 mg/kg | Number of Vaso-occlusive Crises - Part B | 0.6 Number of events | Standard Deviation 0.74 |
Secondary
Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B | 0.2 Number of events | Standard Deviation 0.41 |
| Ticagrelor 0.75 mg/kg | Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B | 0.1 Number of events | Standard Deviation 0.35 |
Secondary
Oral Clearance (CL/F) - Part A
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).
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Oral Clearance (CL/F) - Part A | 22.50 L/h | Standard Deviation 7.531 |
Secondary
Oral Clearance (CL/F) - Part B
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Oral Clearance (CL/F) - Part B | 19.15 L/h | Standard Deviation 6.673 |
Secondary
Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B | 4.52 Percentage of days | Standard Deviation 11.816 |
| Ticagrelor 0.75 mg/kg | Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B | 1.34 Percentage of days | Standard Deviation 3.788 |
Secondary
Percentage of Days of Absence From School or Work (Age >=6) - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Percentage of Days of Absence From School or Work (Age >=6) - Part B | 4.87 Percentage of days | Standard Deviation 10.865 |
| Ticagrelor 0.75 mg/kg | Percentage of Days of Absence From School or Work (Age >=6) - Part B | 5.95 Percentage of days | Standard Deviation 9.494 |
Secondary
Percentage of Days of Analgesic Use (Age >= 4) - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Percentage of Days of Analgesic Use (Age >= 4) - Part B | 16.79 Percentage of days | Standard Deviation 20.838 |
| Ticagrelor 0.75 mg/kg | Percentage of Days of Analgesic Use (Age >= 4) - Part B | 18.56 Percentage of days | Standard Deviation 19.11 |
Secondary
Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B | 12.46 Percentage of days | Standard Deviation 22.502 |
| Ticagrelor 0.75 mg/kg | Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B | 0.54 Percentage of days | Standard Deviation 1.537 |
Secondary
Percentage of Days With Pain (Age >=4) - Part B
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).
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor 0.125 mg/kg | Percentage of Days With Pain (Age >=4) - Part B | 27.01 Percentage of days | Standard Deviation 34.065 |
| Ticagrelor 0.75 mg/kg | Percentage of Days With Pain (Age >=4) - Part B | 31.78 Percentage of days | Standard Deviation 23.731 |
Other Pre-specified
Haemorrhagic Events - Part A
Time frame: From randomisation to Part A (week 0) through Visit 4 (week 2)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 0.125 mg/kg | Haemorrhagic Events - Part A | 0 Number of events |
Other Pre-specified
Haemorrhagic Events - Part B
Time frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 0.125 mg/kg | Haemorrhagic Events - Part B | 0 Number of events |
| Ticagrelor 0.75 mg/kg | Haemorrhagic Events - Part B | 0 Number of events |