Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell DiseasePhase 2HESTIA 1NCT02214121

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

A Phase 2 study testing Ticagrelor Dose 1a + Dose 2a and Ticagrelor Dose 1b + Dose 2b in people with Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease, run by AstraZeneca at 18 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 2 to 17 years
Conditions the study is for: Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease
What is being tested?: Ticagrelor Dose 1a + Dose 2a and Ticagrelor Dose 1b + Dose 2b
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 18 sitesin 6 countries
Study dates: 11 Sep 2014to 27 Feb 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Children aged ≥2 to <18 years of age
Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)

Who cannot join

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.

Trial locations and contacts

18 sites in 6 countries.

Country

City, postcode or hospital

18 sites in 6 countries

United States6 sites

Research Site
Charleston, South Carolina, 29425
Research Site
Chicago, Illinois, 60612
Research Site
Detroit, Michigan, 48201
Research Site
Hershey, Pennsylvania, 17022
Research Site
Orange, California, 92868
Research Site
Philadelphia, Pennsylvania, 19104

Other trials in United States

United Kingdom4 sites

Research Site
Cardiff, CF4 4XN
Research Site
London, E1 1BB
Research Site
London, SE1 7EH
Research Site
Manchester, M13 9PT

Other trials in United Kingdom

Lebanon3 sites

Research Site
Beirut, 1107 2020
Research Site
Beirut, 113-6044
Research Site
Tripoli, 1434

Other trials in Lebanon

Kenya2 sites

Research Site
Kisian, 100
Research Site
Nairobi

Other trials in Kenya

South Africa2 sites

Research Site
Parow, 7500
Research Site
Rondebosch, 7700

Other trials in South Africa

Canada1 site

Research Site
Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: Multicenter, Open-label, Randomised, Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor Followed by a Double-blind, Randomised, Parallel-group, Placebo-controlled 4 Weeks Extension Phase in Paediatric Patients With Sickle Cell Disease

Read the 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.

Conditions: Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease
Being tested: Ticagrelor Dose 1a + Dose 2a, Ticagrelor Dose 1b + Dose 2b
Keywords: sickle cell anemia, paediatric
Medical subject headings: Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ticagrelor Dose 1a + Dose 2aDrug
Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
Ticagrelor Dose 1b + Dose 2bDrug
Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.

Study groups in NCT02214121
Study group	Role	What they receive
Ticagrelor Dose 1a + Dose 2a	Other	Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing. Receives: Drug: Ticagrelor Dose 1a + Dose 2a
Ticagrelor Dose 1b + Dose 2b	Other	Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing. Receives: Drug: Ticagrelor Dose 1b + Dose 2b

What is being measured

The primary outcome is the main question the study is designed to answer.

P2Y12 Reaction Units (PRU) - Part A
Measured: 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
Measured: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
Maximum Plasma Concentration (Cmax) - Part A
Measured: 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
Measured: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
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.
Measured: 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).
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.
Measured: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.

Secondary outcomes (14)

Assessment of Ticagrelor Concentration - Part A
Measured: 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
Measured: 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
AR-C124910XX is the active metabolite of Ticagrelor
Measured: 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 AR-C124910XX Concentration - Part B
AR-C124910XX is the active metabolite of Ticagrelor
Measured: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
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.
Measured: 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).
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.
Measured: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Number of Vaso-occlusive Crises - Part B
Measured: 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
Measured: 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
Measured: 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
Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Measured: 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
Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Measured: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Percentage of Days of Analgesic Use (Age >= 4) - Part B
Measured: 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
Measured: 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
Measured: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 201427 Feb 2017

First posted12 Aug 2014 (estimated)
Study start11 Sep 2014
Primary completion27 Feb 2017
Study completion27 Feb 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell DiseaseStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02214121
Sponsor's protocol ID: D5136C00007
Other IDs: 2014-001006-18, 2014
Acronym: HESTIA 1
Status last verified: Nov 2018
First submitted: 8 Aug 2014
Last updated: 14 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Hsu LL, Sarnaik S, Williams S, Amilon C, Wissmar J, Berggren A; HESTIA1 Investigators. A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study. Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2.
PubMed 30187935
Amilon C, Niazi M, Berggren A, Astrand M, Hamren B. Population Pharmacokinetics/Pharmacodynamics of Ticagrelor in Children with Sickle Cell Disease. Clin Pharmacokinet. 2019 Oct;58(10):1295-1307. doi: 10.1007/s40262-019-00758-0.
PubMed 30972696

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multicenter, Open-label, Randomised, Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor Followed by a Double-blind, Randomised, Parallel-group, Placebo-controlled 4 Weeks Extension Phase in Paediatric Patients With Sickle Cell Disease
ClinicalTrials.gov ID: NCT02214121
Acronym / sponsor ID: HESTIA 1 / D5136C00007
Conditions: Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease
Keywords: sickle cell anemia, paediatric
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 11 Sep 2014 (actual)
Primary completion: 27 Feb 2017 (actual)
Study completion: 27 Feb 2017 (actual)
First posted: 12 Aug 2014 (estimated)
Results: Posted 11 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Ticagrelor Dose 1a + Dose 2a	Other	Drug: Ticagrelor Dose 1a + Dose 2aPart A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.
Ticagrelor Dose 1b + Dose 2b	Other	Drug: Ticagrelor Dose 1b + Dose 2bPart A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

Children aged ≥2 to <18 years of age
Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ticagrelor Dose 1a + Dose 2aTicagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.	Drug	Ticagrelor Dose 1a + Dose 2a
Ticagrelor Dose 1b + Dose 2bTicagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.	Drug	Ticagrelor Dose 1b + Dose 2b

Primary outcome

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.
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.
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).
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.
Area Under the Plasma Concentration Time Curve (AUC) - 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).
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 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.
The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.

14 secondary outcomes

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)
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.
Assessment of AR-C124910XX 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)
Assessment of AR-C124910XX 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.
Oral Clearance (CL/F) - 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).
Oral Clearance (CL/F) - 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.
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).
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).
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).
Percentage of Days With Pain (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).
Mean Intensity of Pain (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).
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).
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).
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).

Results and safety

Results posted to the registry on 11 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A - Ticagrelor	46	39
Part B - Ticagrelor	0	0
Part B - Placebo	0	0

Primary outcome: 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.. Mean (Standard Deviation). Unit: P2Y12 reaction units

Measure	Ticagrelor 0.125 mg/kg n = 14	Ticagrelor 0.75 mg/kg n = 31	Ticagrelor 0.375 mg/kg n = 7	Ticagrelor 0.563 mg/kg n = 18	Ticagrelor 1.125 mg/kg n = 10	Ticagrelor 2.25 mg/kg n = 9	Ticagrelor 0.125 mg/kg Bid n = 14	Ticagrelor 0.563 mg/kg Bid n = 9	Ticagrelor 0.75 mg/kg Bid n = 17
Pre-dose	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 (NA)	205.4 (53.22)	214.7 (48.71)
2 hours post-dose	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	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	343.0 (38.13)	–	318.3 (66.43)	318.0 (NA)	–	–	–	–	–

Population analysed: 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.

Primary outcome: 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.. Mean (Standard Deviation). Unit: P2Y12 reaction units

Measure	Ticagrelor 0.125 mg/kg Bid n = 9	Placebo n = 3
Pre-dose	282.8 (19.26)	313.3 (20.13)
2 hours post-dose	259.6 (61.95)	217.3 (78.34)

Population analysed: 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.

Primary outcome: 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).. Geometric mean (Standard Deviation). Unit: ng/mL

Measure	Ticagrelor 0.125 mg/kg n = 14	Ticagrelor 0.75 mg/kg n = 31	Ticagrelor 0.375 mg/kg n = 7	Ticagrelor 0.563 mg/kg n = 18	Ticagrelor 1.125 mg/kg n = 10	Ticagrelor 2.25 mg/kg n = 9	Ticagrelor 0.125 mg/kg Bid n = 14	Ticagrelor 0.563 mg/kg Bid n = 9	Ticagrelor 0.75 mg/kg Bid n = 17
Value	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)

Population analysed: 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.

Primary outcome: 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.. Geometric mean (Standard Deviation). Unit: ng/mL

Measure	Ticagrelor 0.125 mg/kg Bid n = 9
Value	16.394 (13.3671)

Population analysed: 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.

14 secondary outcomes are reported in the full results.

Adverse events

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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A - Ticagrelor	5 of 45 (11.1%)	22 of 45 (48.9%)	0 of 45
Part B - Ticagrelor	4 of 16 (25%)	12 of 16 (75%)	0 of 16
Part B - Placebo	1 of 7 (14.3%)	5 of 7 (71.4%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30187935Hsu LL, Sarnaik S, Williams S, Amilon C, Wissmar J, Berggren A; HESTIA1 Investigators. A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study. Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2.
Derived from this study: PubMed 30972696Amilon C, Niazi M, Berggren A, Astrand M, Hamren B. Population Pharmacokinetics/Pharmacodynamics of Ticagrelor in Children with Sickle Cell Disease. Clin Pharmacokinet. 2019 Oct;58(10):1295-1307. doi: 10.1007/s40262-019-00758-0.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

18 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, United Kingdom, Lebanon, Kenya, South Africa and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02214121, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2018.