Trial Outcomes & Findings for A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease (NCT NCT02214121)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

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).

Results posted on

2018-12-14

Participant Flow

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.

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)

Participant milestones

Participant milestones
Measure	Part A - Ticagrelor Randomised treatment group for Part A of the study. Relevant for the Part A period.	Part B - Ticagrelor Randomised treatment group for Part B of the study. Relevant for the Part B period.	Part B - Placebo Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part A STARTED	46	0	0
Part A COMPLETED	39	0	0
Part A NOT COMPLETED	7	0	0
Part B STARTED	0	17	8
Part B COMPLETED	0	14	7
Part B NOT COMPLETED	0	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A - Ticagrelor Randomised treatment group for Part A of the study. Relevant for the Part A period.	Part B - Ticagrelor Randomised treatment group for Part B of the study. Relevant for the Part B period.	Part B - Placebo Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part A Patient decision	2	0	0
Part A Dev. of study-specific withdrawal crit.	4	0	0
Part A Other	1	0	0
Part B Patient decision	0	1	0
Part B Dev. of study-specific withdrawal crit.	0	2	0
Part B Lost to Follow-up	0	0	1

Baseline Characteristics

Including only part A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A - Ticagrelor n=45 Participants Actual treatment group for Part A of the study. Relevant for the Part A period.	Part B - Ticagrelor n=16 Participants Actual treatment group for Part B of the study. Relevant for the Part B period.	Part B - Placebo n=7 Participants Actual treatment group for Part B of the study. Relevant for the Part B period.	Total n=68 Participants Total of all reporting groups
Age, Continuous	11.2 Years STANDARD_DEVIATION 3.34 • n=45 Participants • Including only part A	10.2 Years STANDARD_DEVIATION 3.73 • n=16 Participants • Including only part B	9.7 Years STANDARD_DEVIATION 3.35 • n=7 Participants • Including only part B	10.0 Years STANDARD_DEVIATION 3.55 • n=23 Participants • Including only part B
Sex: Female, Male Female	0 Participants Including only part B	9 Participants n=16 Participants • Including only part B	2 Participants n=7 Participants • Including only part B	11 Participants n=23 Participants • Including only part B
Sex: Female, Male Male	0 Participants Including only part B	7 Participants n=16 Participants • Including only part B	5 Participants n=7 Participants • Including only part B	12 Participants n=23 Participants • Including only part B
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants Including only part B	1 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	1 Participants n=23 Participants • Including only part B
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants Including only part B	15 Participants n=16 Participants • Including only part B	7 Participants n=7 Participants • Including only part B	22 Participants n=23 Participants • Including only part B
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants Including only part B	0 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	0 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized White	0 Participants Including only part B	1 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	1 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized Black or African American	0 Participants Including only part B	15 Participants n=16 Participants • Including only part B	7 Participants n=7 Participants • Including only part B	22 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized Asian	0 Participants Including only part B	0 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	0 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants Including only part B	0 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	0 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants Including only part B	0 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	0 Participants n=23 Participants • Including only part B
Race/Ethnicity, Customized Other	0 Participants Including only part B	0 Participants n=16 Participants • Including only part B	0 Participants n=7 Participants • Including only part B	0 Participants n=23 Participants • Including only part B

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=31 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg n=7 Participants Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg n=18 Participants Single dose received at Visit 3	Ticagrelor 1.125 mg/kg n=10 Participants Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg n=9 Participants Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid n=14 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid n=9 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid n=17 Participants Repeated bid treatment between Visit 3 and Visit 4.
P2Y12 Reaction Units (PRU) - Part A Pre-dose	301.6 P2Y12 reaction units Standard Deviation 46.55	268.0 P2Y12 reaction units Standard Deviation 35.95	295.4 P2Y12 reaction units Standard Deviation 42.30	287.7 P2Y12 reaction units Standard Deviation 34.35	283.7 P2Y12 reaction units Standard Deviation 36.88	277.7 P2Y12 reaction units Standard Deviation 39.36	320 P2Y12 reaction units Standard Deviation NA Mean based on one observation.	205.4 P2Y12 reaction units Standard Deviation 53.22	214.7 P2Y12 reaction units Standard Deviation 48.71
P2Y12 Reaction Units (PRU) - Part A 2 hours post-dose	278.2 P2Y12 reaction units Standard Deviation 47.20	138.4 P2Y12 reaction units Standard Deviation 70.68	229.0 P2Y12 reaction units Standard Deviation 64.22	176.2 P2Y12 reaction units Standard Deviation 79.53	128.9 P2Y12 reaction units Standard Deviation 37.68	79.9 P2Y12 reaction units Standard Deviation 47.74	271.2 P2Y12 reaction units Standard Deviation 70.35	102.0 P2Y12 reaction units Standard Deviation 72.53	152.0 P2Y12 reaction units Standard Deviation 72.35
P2Y12 Reaction Units (PRU) - Part A 6 hours post-dose	276.0 P2Y12 reaction units Standard Deviation 75.43	189.0 P2Y12 reaction units Standard Deviation 69.84	266.0 P2Y12 reaction units Standard Deviation 57.98	190.4 P2Y12 reaction units Standard Deviation 47.78	191.2 P2Y12 reaction units Standard Deviation 57.59	141.7 P2Y12 reaction units Standard Deviation 69.58	—	—	—
P2Y12 Reaction Units (PRU) - Part A 8 hours post-dose	343.0 P2Y12 reaction units Standard Deviation 38.13	—	318.3 P2Y12 reaction units Standard Deviation 66.43	318.0 P2Y12 reaction units Standard Deviation NA Mean based on one observation.	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=3 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
P2Y12 Reaction Units (PRU) - Part B Pre-dose	282.8 P2Y12 reaction units Standard Deviation 19.26	313.3 P2Y12 reaction units Standard Deviation 20.13	—	—	—	—	—	—	—
P2Y12 Reaction Units (PRU) - Part B 2 hours post-dose	259.6 P2Y12 reaction units Standard Deviation 61.95	217.3 P2Y12 reaction units Standard Deviation 78.34	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=31 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg n=7 Participants Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg n=18 Participants Single dose received at Visit 3	Ticagrelor 1.125 mg/kg n=10 Participants Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg n=9 Participants Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid n=14 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid n=9 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid n=17 Participants Repeated bid treatment between Visit 3 and Visit 4.
Maximum Plasma Concentration (Cmax) - Part A	15.240 ng/mL Standard Deviation 15.2709	162.961 ng/mL Standard Deviation 84.9230	52.069 ng/mL Standard Deviation 34.4115	96.031 ng/mL Standard Deviation 51.4902	269.174 ng/mL Standard Deviation 162.2147	566.550 ng/mL Standard Deviation 225.9447	13.973 ng/mL Standard Deviation 15.3652	111.367 ng/mL Standard Deviation 81.1597	157.216 ng/mL Standard Deviation 114.8138

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Maximum Plasma Concentration (Cmax) - Part B	16.394 ng/mL Standard Deviation 13.3671	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=31 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg n=7 Participants Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg n=18 Participants Single dose received at Visit 3	Ticagrelor 1.125 mg/kg n=10 Participants Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg n=9 Participants Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid n=14 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid n=9 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid n=17 Participants Repeated bid treatment between Visit 3 and Visit 4.
Area Under the Plasma Concentration Time Curve (AUC) - Part A	161.9 ng*h/mL Standard Deviation 72.24	1151.9 ng*h/mL Standard Deviation 308.39	437.5 ng*h/mL Standard Deviation 262.24	879.3 ng*h/mL Standard Deviation 236.12	1638.7 ng*h/mL Standard Deviation 521.80	2850.9 ng*h/mL Standard Deviation 1277.39	161.9 ng*h/mL Standard Deviation 72.24	913.5 ng*h/mL Standard Deviation 208.82	1022.4 ng*h/mL Standard Deviation 287.32

PRIMARY outcome

Timeframe: 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.

The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Area Under the Plasma Concentration Time Curve (AUC) - Part B	160.6 ng*h/mL Standard Deviation 88.58	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=31 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg n=7 Participants Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg n=18 Participants Single dose received at Visit 3	Ticagrelor 1.125 mg/kg n=10 Participants Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg n=9 Participants Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid n=14 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid n=9 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid n=17 Participants Repeated bid treatment between Visit 3 and Visit 4.
Assessment of Ticagrelor Concentration - Part A Pre-dose	—	—	—	—	—	—	2.170 ng/mL Standard Deviation NA Mean based on one observation.	31.937 ng/mL Standard Deviation 48.6501	28.066 ng/mL Standard Deviation 27.1344
Assessment of Ticagrelor Concentration - Part A 1 hour post-dose	12.713 ng/mL Standard Deviation 16.0627	104.243 ng/mL Standard Deviation 103.1502	34.069 ng/mL Standard Deviation 42.3746	33.294 ng/mL Standard Deviation 55.4258	182.558 ng/mL Standard Deviation 188.4254	390.568 ng/mL Standard Deviation 294.2189	—	80.414 ng/mL Standard Deviation 75.9675	151.520 ng/mL Standard Deviation 116.0079
Assessment of Ticagrelor Concentration - Part A 2 hours post-dose	11.465 ng/mL Standard Deviation 8.7427	107.729 ng/mL Standard Deviation 62.8343	37.782 ng/mL Standard Deviation 31.6890	74.626 ng/mL Standard Deviation 50.7053	162.435 ng/mL Standard Deviation 161.8489	426.804 ng/mL Standard Deviation 212.5385	13.973 ng/mL Standard Deviation 15.3652	102.166 ng/mL Standard Deviation 78.0785	101.618 ng/mL Standard Deviation 65.2415
Assessment of Ticagrelor Concentration - Part A 4 hours post-dose	6.647 ng/mL Standard Deviation 4.4533	75.907 ng/mL Standard Deviation 31.2786	20.122 ng/mL Standard Deviation 9.9383	51.005 ng/mL Standard Deviation 24.6435	118.217 ng/mL Standard Deviation 42.0873	188.383 ng/mL Standard Deviation 111.9267	—	—	—
Assessment of Ticagrelor Concentration - Part A 6 hours post-dose	3.663 ng/mL Standard Deviation 3.4061	52.966 ng/mL Standard Deviation 29.0297	19.435 ng/mL Standard Deviation 15.7259	45.502 ng/mL Standard Deviation 17.8950	69.708 ng/mL Standard Deviation 44.3168	125.279 ng/mL Standard Deviation 89.0005	—	—	—
Assessment of Ticagrelor Concentration - Part A 8 hours post-dose	3.880 ng/mL Standard Deviation 3.3171	—	15.699 ng/mL Standard Deviation 20.7596	15.691 ng/mL Standard Deviation 15.1392	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Assessment of Ticagrelor Concentration - Part B Pre-dose	2.478 ng/mL Standard Deviation 3.9580	—	—	—	—	—	—	—	—
Assessment of Ticagrelor Concentration - Part B 1 hour post-dose	9.677 ng/mL Standard Deviation 9.4275	—	—	—	—	—	—	—	—
Assessment of Ticagrelor Concentration - Part B 2 hours post-dose	14.144 ng/mL Standard Deviation 12.4711	—	—	—	—	—	—	—	—
Assessment of Ticagrelor Concentration - Part B 4 hours post-dose	9.605 ng/mL Standard Deviation 14.4979	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

AR-C124910XX is the active metabolite of Ticagrelor

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=31 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg n=7 Participants Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg n=18 Participants Single dose received at Visit 3	Ticagrelor 1.125 mg/kg n=10 Participants Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg n=9 Participants Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid n=14 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid n=9 Participants Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid n=17 Participants Repeated bid treatment between Visit 3 and Visit 4.
Assessment of AR-C124910XX Concentration - Part A 1 hour post-dose	1.782 ng/mL Standard Deviation 1.6604	16.302 ng/mL Standard Deviation 22.4614	4.577 ng/mL Standard Deviation 7.8610	3.708 ng/mL Standard Deviation 13.3332	30.070 ng/mL Standard Deviation 44.2950	63.088 ng/mL Standard Deviation 84.2091	—	24.945 ng/mL Standard Deviation 15.6547	43.986 ng/mL Standard Deviation 29.8127
Assessment of AR-C124910XX Concentration - Part A Pre-dose	—	—	—	—	—	—	1.250 ng/mL Standard Deviation NA Mean based on one observation.	17.380 ng/mL Standard Deviation 10.0399	20.359 ng/mL Standard Deviation 15.0788
Assessment of AR-C124910XX Concentration - Part A 2 hours post-dose	2.681 ng/mL Standard Deviation 2.0733	33.256 ng/mL Standard Deviation 25.3854	11.757 ng/mL Standard Deviation 13.3322	15.918 ng/mL Standard Deviation 17.4849	52.932 ng/mL Standard Deviation 69.1056	149.772 ng/mL Standard Deviation 71.3624	4.026 ng/mL Standard Deviation 4.7624	37.013 ng/mL Standard Deviation 32.7650	44.690 ng/mL Standard Deviation 31.6577
Assessment of AR-C124910XX Concentration - Part A 4 hours post-dose	2.071 ng/mL Standard Deviation 1.2770	29.860 ng/mL Standard Deviation 13.8726	7.630 ng/mL Standard Deviation 6.3730	17.015 ng/mL Standard Deviation 7.9272	50.887 ng/mL Standard Deviation 25.6964	101.370 ng/mL Standard Deviation 44.6207	—	—	—
Assessment of AR-C124910XX Concentration - Part A 6 hours post-dose	1.646 ng/mL Standard Deviation 1.0427	25.276 ng/mL Standard Deviation 10.8318	9.762 ng/mL Standard Deviation 2.3304	16.703 ng/mL Standard Deviation 5.8115	35.716 ng/mL Standard Deviation 22.3351	76.941 ng/mL Standard Deviation 39.9167	—	—	—
Assessment of AR-C124910XX Concentration - Part A 8 hours post-dose	1.715 ng/mL Standard Deviation 1.0226	—	6.176 ng/mL Standard Deviation 6.3168	9.232 ng/mL Standard Deviation 2.5385	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

AR-C124910XX is the active metabolite of Ticagrelor

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Assessment of AR-C124910XX Concentration - Part B Pre-dose	1.810 ng/mL Standard Deviation 1.1213	—	—	—	—	—	—	—	—
Assessment of AR-C124910XX Concentration - Part B 1 hour post-dose	2.865 ng/mL Standard Deviation 1.6443	—	—	—	—	—	—	—	—
Assessment of AR-C124910XX Concentration - Part B 2 hours post-dose	4.160 ng/mL Standard Deviation 3.1503	—	—	—	—	—	—	—	—
Assessment of AR-C124910XX Concentration - Part B 4 hours post-dose	3.953 ng/mL Standard Deviation 4.1179	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=45 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Oral Clearance (CL/F) - Part A	22.50 L/h Standard Deviation 7.531	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=9 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Oral Clearance (CL/F) - Part B	19.15 L/h Standard Deviation 6.673	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=15 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Number of Vaso-occlusive Crises - Part B	1.0 Number of events Standard Deviation 2.00	0.6 Number of events Standard Deviation 0.74	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=15 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B	0.2 Number of events Standard Deviation 0.41	0.1 Number of events Standard Deviation 0.35	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=15 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
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	1.34 Percentage of days Standard Deviation 3.788	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Percentage of Days With Pain (Age >=4) - Part B	27.01 Percentage of days Standard Deviation 34.065	31.78 Percentage of days Standard Deviation 23.731	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Mean Intensity of Pain (Age >=4) - Part B Overall - Part B	1.40 Mean score on scale Standard Deviation 2.027	0.87 Mean score on scale Standard Deviation 0.493	—	—	—	—	—	—	—
Mean Intensity of Pain (Age >=4) - Part B 1st week	1.64 Mean score on scale Standard Deviation 2.603	1.36 Mean score on scale Standard Deviation 0.827	—	—	—	—	—	—	—
Mean Intensity of Pain (Age >=4) - Part B 2nd week	1.11 Mean score on scale Standard Deviation 2.236	0.38 Mean score on scale Standard Deviation 0.525	—	—	—	—	—	—	—
Mean Intensity of Pain (Age >=4) - Part B 3rd week	1.06 Mean score on scale Standard Deviation 1.881	0.67 Mean score on scale Standard Deviation 1.116	—	—	—	—	—	—	—
Mean Intensity of Pain (Age >=4) - Part B 4th week	1.46 Mean score on scale Standard Deviation 2.624	0.83 Mean score on scale Standard Deviation 0.901	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Percentage of Days of Analgesic Use (Age >= 4) - Part B	16.79 Percentage of days Standard Deviation 20.838	18.56 Percentage of days Standard Deviation 19.110	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=14 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=8 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B	12.46 Percentage of days Standard Deviation 22.502	0.54 Percentage of days Standard Deviation 1.537	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=11 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=6 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Percentage of Days of Absence From School or Work (Age >=6) - Part B	4.87 Percentage of days Standard Deviation 10.865	5.95 Percentage of days Standard Deviation 9.494	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=45 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Haemorrhagic Events - Part A	0 Number of events	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ticagrelor 0.125 mg/kg n=16 Participants Single dose received at Visit 2.	Ticagrelor 0.75 mg/kg n=7 Participants Single dose received at Visit 2.	Ticagrelor 0.375 mg/kg Single dose received at Visit 3.	Ticagrelor 0.563 mg/kg Single dose received at Visit 3	Ticagrelor 1.125 mg/kg Single dose received at Visit 3.	Ticagrelor 2.25 mg/kg Single dose received at Visit 3.	Ticagrelor 0.125 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.563 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.	Ticagrelor 0.75 mg/kg Bid Repeated bid treatment between Visit 3 and Visit 4.
Haemorrhagic Events - Part B	0 Number of events	0 Number of events	—	—	—	—	—	—	—

Adverse Events

Part A - Ticagrelor

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Part B - Ticagrelor

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Part B - Placebo

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A - Ticagrelor n=45 participants at risk Randomised treatment group for Part A of the study. Relevant for the Part A period.	Part B - Ticagrelor n=16 participants at risk Randomised treatment group for Part B of the study. Relevant for the Part B period.	Part B - Placebo n=7 participants at risk Randomised treatment group for Part B of the study. Relevant for the Part B period.
Blood and lymphatic system disorders Sickle cell anemia with crisis	6.7% 3/45 • Number of events 3 • 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.	18.8% 3/16 • Number of events 3 • 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.	14.3% 1/7 • Number of events 1 • 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.
Infections and infestations Gastroenteritis viral	2.2% 1/45 • Number of events 1 • 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.	0.00% 0/16 • 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.	0.00% 0/7 • 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.
Respiratory, thoracic and mediastinal disorders Acute chest syndrome	2.2% 1/45 • Number of events 1 • 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.	6.2% 1/16 • Number of events 1 • 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.	0.00% 0/7 • 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

Additional Information

Brilinta Global Clinical Lead

AstraZeneca

Phone: +46 31 776 1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER