Trial Outcomes & Findings for A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib (NCT NCT00777036)

Last Updated: 2025-08-29

Results Overview

Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

133 participants

Primary outcome timeframe

From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Results posted on

2025-08-29

Participant Flow

Participants were enrolled at 80 sites (Argentina, Australia, Brazil, Canada, France, Germany, Great Britain, India, Italy, Korea, Mexico, Netherlands, Romania, Russia, Singapore, South Africa, Spain, and USA).

The PK sub-study analysis is not part of the pre-specified primary and secondary outcome measures.

Participant milestones

Participant milestones
Measure	Cohort 1 Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 2 Children and adolescents with Ph+ ALL, AP-CML or BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	PK Sub-Study Children and adolescents received powder for oral suspension (PFOS) at a dose of 90 mg/m2 QD to evaluate the pharmacokinetics of dasatinib.
On Treatment STARTED	29	17	84	0
On Treatment COMPLETED	0	0	0	0
On Treatment NOT COMPLETED	29	17	84	0
PK Sub-Study STARTED	0	0	0	7
PK Sub-Study COMPLETED	0	0	0	7
PK Sub-Study NOT COMPLETED	0	0	0	0
Follow-Up STARTED	21	12	47	0
Follow-Up COMPLETED	12	3	25	0
Follow-Up NOT COMPLETED	9	9	22	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 2 Children and adolescents with Ph+ ALL, AP-CML or BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
On Treatment Reached 18 years of age and transitioned to commercial drug	13	7	42
On Treatment Administrative Reason By Sponsor	1	0	9
On Treatment Failure to Meet Study Criteria	0	1	4
On Treatment Pregnancy	1	0	1
On Treatment Non-compliance with Study Drug	1	0	1
On Treatment Maximum Clinical Benefit	2	0	5
On Treatment Withdrawal by Subject	0	2	2
On Treatment Participant Request to Discontinue Study Treatment	4	0	6
On Treatment Death	0	2	0
On Treatment Study Drug Toxicity	1	0	4
On Treatment Progressive Disease	6	4	7
On Treatment Not Reported	0	0	2
On Treatment Site Closed	0	1	1
Follow-Up Withdrawal by Subject	0	0	5
Follow-Up Death	1	9	0
Follow-Up Lost to Follow-up	3	0	0
Follow-Up Reason Not Specified	4	0	13
Follow-Up Missing - Administrative Reasons in Russia	1	0	4

Baseline Characteristics

A Phase II Study of Dasatinib in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML) or With Ph+ Leukemias Resistant or Intolerant to Imatinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 2 n=17 Participants Children and adolescents with Ph+ ALL, AP-CML or BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	PK Sub-Study n=3 Participants Children and adolescents received powder for oral suspension (PFOS) at a dose of 90 mg/m2 QD to evaluate the pharmacokinetics of dasatinib.	Total n=133 Participants Total of all reporting groups
Age, Continuous	12.60 years STANDARD_DEVIATION 4.774 • n=5 Participants	12.10 years STANDARD_DEVIATION 3.680 • n=7 Participants	11.95 years STANDARD_DEVIATION 4.418 • n=5 Participants	13.33 years STANDARD_DEVIATION 1.154 • n=4 Participants	12.05 years STANDARD_DEVIATION 4.255 • n=21 Participants
Age, Customized < 2 years	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Age, Customized >= 2 to < 7 years	3 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants	0 participants n=4 Participants	15 participants n=21 Participants
Age, Customized >= 7 to < 12 years	6 participants n=5 Participants	6 participants n=7 Participants	28 participants n=5 Participants	0 participants n=4 Participants	40 participants n=21 Participants
Age, Customized >= 12 to < 18 years	17 participants n=5 Participants	9 participants n=7 Participants	44 participants n=5 Participants	3 participants n=4 Participants	73 participants n=21 Participants
Age, Customized >= 18 years	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	9 Participants n=7 Participants	39 Participants n=5 Participants	2 Participants n=4 Participants	66 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	8 Participants n=7 Participants	45 Participants n=5 Participants	1 Participants n=4 Participants	67 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	0 Participants n=4 Participants	7 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	20 Participants n=5 Participants	1 Participants n=4 Participants	25 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	17 Participants n=7 Participants	59 Participants n=5 Participants	2 Participants n=4 Participants	101 Participants n=21 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	13 Participants n=7 Participants	56 Participants n=5 Participants	2 Participants n=4 Participants	91 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	3 Participants n=7 Participants	23 Participants n=5 Participants	0 Participants n=4 Participants	32 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 1

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Major Cytogenetic Response (MCyR) Rate	89.7 percentage of participants Interval 72.6 to 97.8	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 2

Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1 n=17 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Hematologic Response (CHR) Rate	29.4 percentage of participants Interval 10.3 to 56.0	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: Primary efficacy endpoint pre-specified only for participants treated in Cohort 3

Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.

Outcome measures

Outcome measures
Measure	Cohort 1 n=84 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Cytogenetic Response (CCyR) Rate	94.0 percentage of participants Interval 86.7 to 98.0	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: Secondary efficacy endpoint pre-specified only for participants treated in Cohort 2

Major Cytogenetic Response (MCyR) rate was defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response. The percentage of treated participants in each arm with MCyR is reported.

Outcome measures

Outcome measures
Measure	Cohort 1 n=17 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Major Cytogenetic Response (MCyR) Rate in Cohort 2	52.9 percentage of participants Interval 27.8 to 77.0	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: Secondary efficacy endpoint pre-specified only for participants treated in Cohort 1 and Cohort 3

Complete Hematologic Response (CHR) rate defined as the proportion of all treated participants who achieve a confirmed CHR while on-study. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood. The percentage of treated participants in each arm with CHR is reported.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3	93.1 percentage of participants Interval 77.2 to 99.2	96.4 percentage of participants Interval 89.9 to 99.3	—	—	—

SECONDARY outcome

Timeframe: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)

Population: All treated participants

The number of participants achieving their best on-study cytogenetic response was reported as a percentage of all treated participants in that arm. (Based on \>=20 Metaphases)

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Rate of Best Cytogenetic Response Complete (0%)	82.8 percentage of participants	29.4 percentage of participants	94.0 percentage of participants	96.1 percentage of participants	90.9 percentage of participants
Rate of Best Cytogenetic Response Partial (>0% - 35%)	6.9 percentage of participants	23.5 percentage of participants	2.4 percentage of participants	2.0 percentage of participants	3.0 percentage of participants
Rate of Best Cytogenetic Response Minor (>35% - 65%)	3.4 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Rate of Best Cytogenetic Response Minimal (>65% - 95%)	3.4 percentage of participants	0 percentage of participants	1.2 percentage of participants	2.0 percentage of participants	0 percentage of participants
Rate of Best Cytogenetic Response No Response (>95% - 100%)	0 percentage of participants	5.9 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Rate of Best Cytogenetic Response Unable to Determine	3.4 percentage of participants	41.2 percentage of participants	2.4 percentage of participants	0 percentage of participants	6.1 percentage of participants

SECONDARY outcome

Timeframe: From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months)

Population: All treated participants with MCyR

Time to MCyR is defined as the time from first dose of dasatinib until the first day MCyR criteria are met, computed only for participants whose best response is MCyR. (Based on \>=20 Metaphases)

Outcome measures

Outcome measures
Measure	Cohort 1 n=26 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=9 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=81 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=50 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=31 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Time to Major Cytogenetic Response (MCyR)	3.1 months Interval 2.8 to 4.1	1.6 months Interval 0.5 to 5.7	3.0 months Interval 2.9 to 4.3	3.3 months Interval 2.9 to 5.6	3.0 months Interval 2.8 to 5.0

SECONDARY outcome

Timeframe: From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months)

Population: All treated participants with MCyR

Duration of MCyR will be computed from the first day criteria are met for MCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases)

Outcome measures

Outcome measures
Measure	Cohort 1 n=26 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=9 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=81 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=50 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=31 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Duration of Major Cytogenetic Response (MCyR)	NA months Interval 54.9 to Insufficient number of participants with events	11.2 months Interval 0.3 to Insufficient number of participants with events	NA months Interval 52.7 to Insufficient number of participants with events	NA months Interval 52.7 to Insufficient number of participants with events	NA months Insufficient number of participants with events

SECONDARY outcome

Timeframe: From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months)

Population: All treated participants with CCyR

Time to CCyR is defined as the time from first dose of dasatinib until the first day CCyR criteria are met, computed only for participants whose best response is CCyR. (Based on \>=20 Metaphases)

Outcome measures

Outcome measures
Measure	Cohort 1 n=24 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=5 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=79 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=49 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=30 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Time to Complete Cytogenetic Response (CCyR)	3.9 months Interval 2.8 to 5.6	1.6 months Interval 0.5 to 5.7	5.6 months Interval 5.0 to 6.0	5.7 months Interval 3.7 to 6.2	5.6 months Interval 3.1 to 6.0

SECONDARY outcome

Timeframe: From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months)

Population: All treated participants who achieved CCyR

Duration of CCyR will be computed from the first day criteria are met for CCyR until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. (Based on \>=20 Metaphases)

Outcome measures

Outcome measures
Measure	Cohort 1 n=24 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=5 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=79 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=49 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=30 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Duration of Complete Cytogenetic Response (CCyR)	NA months Interval 54.9 to Insufficient number of participants with events	NA months Interval 1.0 to Insufficient number of participants with events.	NA months Interval 49.9 to Insufficient number of participants with events	NA months Interval 49.9 to Insufficient number of participants with events	NA months Insufficient number of participants with events

SECONDARY outcome

Timeframe: 174 Months

Population: All treated participants

PFS is defined as time from the first dosing date until the time PD is first documented by the investigator or death. Participants who die without a reported date of progression will be considered to have progressed on the date of death. Participants who neither progress nor die will be censored on the date of their last cytogenetic or hematologic assessment. Based on Kaplan-Meier methodology. Disease Progression was defined as any of the following criteria: -For CP-CML, progression to AP-CML or BP-CML while at highest tolerated dose -Increasing WBC -Loss of CHR (defined as any of the following: WBC count rises to \>20.0x10\^9/L; Platelet count rises to \>600x10\^9/L; appearance of extramedullary disease; appearance of \>5% myelocytes+metamyelocytes in blood; appearance of blasts/promyelocytes in peripheral blood) -Loss of MCyR or increase in Ph+ bone marrow cells by \>=30% from nadir -Death from any case during treatment.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Progression-Free Survival (PFS)	NA Months Interval 87.0 to Insufficient number of participants with events	6.67 Months Interval 0.95 to 12.16	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months)

Population: All treated participants with CHR

Time to CHR is defined as the time from first dose of dasatinib until the first day CHR criteria are met, provided they are confirmed 4 weeks later, computed only for participants whose best response is CHR.

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=5 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=81 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=30 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Time to Complete Hematologic Response (CHR)	0.7 months Interval 0.5 to 1.8	2.5 months Interval 0.5 to 2.8	1.2 months Interval 0.9 to 1.4	1.2 months Interval 0.9 to 1.4	1.0 months Interval 0.7 to 1.8

SECONDARY outcome

Timeframe: From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months)

Population: All treated participants with CCyR

Duration of CHR will be computed from the first day all criteria are met for CHR, provided they are confirmed 4 weeks later, until the date progressive disease (PD) is reported (or treatment is discontinued for PD) or death. Participants who neither discontinue due to PD nor die will be censored on the date of their last hematologic assessment.

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=5 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=81 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=30 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Duration of Complete Hemotologic Response (CHR)	NA months Insufficient number of participants with events	NA months Interval 1.9 to Insufficient number of participants with events	NA months Insufficient number of participants with events	NA months Insufficient number of participants with events	NA months Insufficient number of participants with events

SECONDARY outcome

Timeframe: 168 Months

Population: All treated participants with response of CCyR or CHR

Disease free survival is defined as time from CCyR for participants with newly diagnosed chronic phase CML and for participants with chronic phase CML who are resistant or intolerant to imatinib (cohort 3 and cohort 1), and as time from CHR for participants with advanced phase CML and PH + ALL (cohort 2) until the time progression is first documented by the investigator or death from any cause. Based on Kaplan-Meier methodology. (CML: Chronic Myeloid Leukemia).

Outcome measures

Outcome measures
Measure	Cohort 1 n=24 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=5 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=79 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=49 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=30 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Disease-Free Survival	NA Months Interval 75.83 to Insufficient number of participants with events	NA Months Interval 1.87 to Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: 174 Months

Population: All treated participants

OS is defined as time from the first dosing date until the time of death. All participants will be followed yearly for survival for up to 5 years after treatment discontinuation. Participants who have not died or who are lost to follow-up will be censored on the last date the participant is known to be alive. Based on Kaplan-Meier methodology using graphs.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Overall Survival (OS)	NA Months Insufficient number of participants with events	13.63 Months Interval 4.67 to Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: From date of first treatment to date of MMR (assessed up to Jan 2025, approximately 15 years and 10 months)

Population: All treated participants

Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). MMR for participants with the p210 BCR-ABL transcript variant was defined as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale. In this study, ABL was used as the control-gene. For a participant with the p190 BCR-ABL transcript variant (occurring in Cohort 2 only), on-study assessments were compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline was considered an MMR.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Major Molecular Response (MMR) Rate	69.0 percentage of participants Interval 49.2 to 84.7	29.4 percentage of participants Interval 10.3 to 56.0	84.5 percentage of participants Interval 75.0 to 91.5	90.2 percentage of participants Interval 78.6 to 96.7	75.8 percentage of participants Interval 57.7 to 88.9

SECONDARY outcome

Timeframe: From date of first treatment to date of CMR (assessed up to Jan 2025, approximately 15 years and 10 months)

Population: All treated participants

Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Molecular Response (CMR) Rate	27.6 percentage of participants Interval 12.7 to 47.2	11.8 percentage of participants Interval 1.5 to 36.4	42.9 percentage of participants Interval 32.1 to 54.1	49.0 percentage of participants Interval 34.8 to 63.4	33.3 percentage of participants Interval 18.0 to 51.8

SECONDARY outcome

Timeframe: 24 months

Population: All treated participants

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Major Cytogenetic Response (MCyR) Rate up to 2 Years 12 months	89.7 percentage of participants Interval 72.6 to 97.8	58.8 percentage of participants Interval 32.9 to 81.6	96.4 percentage of participants Interval 89.9 to 99.3	98.0 percentage of participants Interval 89.6 to 100.0	93.9 percentage of participants Interval 79.8 to 99.3
Major Cytogenetic Response (MCyR) Rate up to 2 Years 24 months	89.7 percentage of participants Interval 72.6 to 97.8	58.8 percentage of participants Interval 32.9 to 81.6	96.4 percentage of participants Interval 89.9 to 99.3	98.0 percentage of participants Interval 89.6 to 100.0	93.9 percentage of participants Interval 79.8 to 99.3

SECONDARY outcome

Timeframe: 24 months

Population: All treated participants

Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The percentage of treated participants with CCyR is reported by arm.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Cytogenetic Response (CCyR) Rate up to 2 Years 24 months	82.8 percentage of participants Interval 64.2 to 94.2	41.2 percentage of participants Interval 18.4 to 67.1	94.0 percentage of participants Interval 86.7 to 98.0	96.1 percentage of participants Interval 86.5 to 99.5	90.9 percentage of participants Interval 75.7 to 98.1
Complete Cytogenetic Response (CCyR) Rate up to 2 Years 12 months	75.9 percentage of participants Interval 56.5 to 89.7	41.2 percentage of participants Interval 18.4 to 67.1	92.9 percentage of participants Interval 85.1 to 97.3	96.1 percentage of participants Interval 86.5 to 99.5	87.9 percentage of participants Interval 71.8 to 96.6

SECONDARY outcome

Timeframe: 90 months

Population: All treated participants

Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time qPCR. MMR for participants with the p210 BCR-ABL transcript variant is defined according to the recommendations of Hughes et al. as a ratio BCR-ABL/ABL \<= 10-3 or 0.1% on the international scale proposed by the authors. The standardized baseline, as established in the IRIS trial, is taken to represent 100% on the international scale and a 3-log reduction in ratio (BCR-ABL transcripts/ABL or BCR) from the standardized baseline (MMR) is fixed at 0.1%. In this study, ABL or other housekeeping gene, will be used as the control-gene. For a participant with the p190 BCR-ABL transcript variant, on-study assessments will be compared to the participant's individual baseline BCR-ABL/ABL ratio and a reduction to \< 0.1% or a 3-log reduction from baseline will be considered an MMR. The percentage of treated participants with MMR is reported by arm.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Major Molecular Response (MMR) Rate up to 7.5 Years 36 months	62.1 percentage of participants Interval 42.3 to 79.3	29.4 percentage of participants Interval 10.3 to 56.0	77.4 percentage of participants Interval 67.0 to 85.8	82.4 percentage of participants Interval 69.1 to 91.6	69.7 percentage of participants Interval 51.3 to 84.4
Major Molecular Response (MMR) Rate up to 7.5 Years 12 months	41.4 percentage of participants Interval 23.5 to 61.1	29.4 percentage of participants Interval 10.3 to 56.0	52.4 percentage of participants Interval 41.2 to 63.4	56.9 percentage of participants Interval 42.2 to 70.7	45.5 percentage of participants Interval 28.1 to 63.6
Major Molecular Response (MMR) Rate up to 7.5 Years 24 months	55.2 percentage of participants Interval 35.7 to 73.6	29.4 percentage of participants Interval 10.3 to 56.0	70.2 percentage of participants Interval 59.3 to 79.7	74.5 percentage of participants Interval 60.4 to 85.7	63.6 percentage of participants Interval 45.1 to 79.6
Major Molecular Response (MMR) Rate up to 7.5 Years 48 months	62.1 percentage of participants Interval 42.3 to 79.3	29.4 percentage of participants Interval 10.3 to 56.0	82.1 percentage of participants Interval 72.3 to 89.6	88.2 percentage of participants Interval 76.1 to 95.6	72.7 percentage of participants Interval 54.5 to 86.7
Major Molecular Response (MMR) Rate up to 7.5 Years 60 months	65.5 percentage of participants Interval 45.7 to 82.1	29.4 percentage of participants Interval 10.3 to 56.0	83.3 percentage of participants Interval 73.6 to 90.6	90.2 percentage of participants Interval 78.6 to 96.7	72.7 percentage of participants Interval 54.5 to 86.7
Major Molecular Response (MMR) Rate up to 7.5 Years 72 months	65.5 percentage of participants Interval 45.7 to 82.1	29.4 percentage of participants Interval 10.3 to 56.0	84.5 percentage of participants Interval 75.0 to 91.5	90.2 percentage of participants Interval 78.6 to 96.7	75.8 percentage of participants Interval 57.7 to 88.9
Major Molecular Response (MMR) Rate up to 7.5 Years 84 months	65.5 percentage of participants Interval 45.7 to 82.1	29.4 percentage of participants Interval 10.3 to 56.0	84.5 percentage of participants Interval 75.0 to 91.5	90.2 percentage of participants Interval 78.6 to 96.7	75.8 percentage of participants Interval 57.7 to 88.9
Major Molecular Response (MMR) Rate up to 7.5 Years 90 months	69.0 percentage of participants Interval 49.2 to 84.7	29.4 percentage of participants Interval 10.3 to 56.0	84.5 percentage of participants Interval 75.0 to 91.5	90.2 percentage of participants Interval 78.6 to 96.7	75.8 percentage of participants Interval 57.7 to 88.9

SECONDARY outcome

Timeframe: 90 months

Population: All treated participants

Molecular response will be assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (qPCR). (CMR) is defined as absence of BCR-ABL rearrangements by real-time qPCR analysis. The percentage of treated participants with CMR is reported by arm.

Outcome measures

Outcome measures
Measure	Cohort 1 n=29 Participants Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=17 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3 n=84 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD or powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 Participants Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.
Complete Molecular Response (CMR) Rate up to 7.5 Years 36 months	17.2 percentage of participants Interval 5.8 to 35.8	11.8 percentage of participants Interval 1.5 to 36.4	28.6 percentage of participants Interval 19.2 to 39.5	33.3 percentage of participants Interval 20.8 to 47.9	21.2 percentage of participants Interval 9.0 to 38.9
Complete Molecular Response (CMR) Rate up to 7.5 Years 12 months	6.9 percentage of participants Interval 0.8 to 22.8	5.9 percentage of participants Interval 0.1 to 28.7	8.3 percentage of participants Interval 3.4 to 16.4	9.8 percentage of participants Interval 3.3 to 21.4	6.1 percentage of participants Interval 0.7 to 20.2
Complete Molecular Response (CMR) Rate up to 7.5 Years 24 months	17.2 percentage of participants Interval 5.8 to 35.8	5.9 percentage of participants Interval 0.1 to 28.7	25.0 percentage of participants Interval 16.2 to 35.6	33.3 percentage of participants Interval 20.8 to 47.9	12.1 percentage of participants Interval 3.4 to 28.2
Complete Molecular Response (CMR) Rate up to 7.5 Years 48 months	24.1 percentage of participants Interval 10.3 to 43.5	11.8 percentage of participants Interval 1.5 to 36.4	34.5 percentage of participants Interval 24.5 to 45.7	43.1 percentage of participants Interval 29.3 to 57.8	21.2 percentage of participants Interval 9.0 to 38.9
Complete Molecular Response (CMR) Rate up to 7.5 Years 60 months	24.1 percentage of participants Interval 10.3 to 43.5	11.8 percentage of participants Interval 1.5 to 36.4	40.5 percentage of participants Interval 29.9 to 51.7	47.1 percentage of participants Interval 32.9 to 61.5	30.3 percentage of participants Interval 15.6 to 48.7
Complete Molecular Response (CMR) Rate up to 7.5 Years 72 months	24.1 percentage of participants Interval 10.3 to 43.5	11.8 percentage of participants Interval 1.5 to 36.4	41.7 percentage of participants Interval 31.0 to 52.9	49.0 percentage of participants Interval 34.8 to 63.4	30.3 percentage of participants Interval 15.6 to 48.7
Complete Molecular Response (CMR) Rate up to 7.5 Years 84 months	24.1 percentage of participants Interval 10.3 to 43.5	11.8 percentage of participants Interval 1.5 to 36.4	42.9 percentage of participants Interval 32.1 to 54.1	49.0 percentage of participants Interval 34.8 to 63.4	33.3 percentage of participants Interval 18.0 to 51.8
Complete Molecular Response (CMR) Rate up to 7.5 Years 90 months	27.6 percentage of participants Interval 12.7 to 47.2	11.8 percentage of participants Interval 1.5 to 36.4	42.9 percentage of participants Interval 32.1 to 54.1	49.0 percentage of participants Interval 34.8 to 63.4	33.3 percentage of participants Interval 18.0 to 51.8

Adverse Events

Cohort 1

Serious events: 16 serious events

Other events: 27 other events

Deaths: 1 deaths

Cohort 2: BP-CML Only

Serious events: 7 serious events

Other events: 7 other events

Deaths: 4 deaths

Cohort 2: Ph + ALL Only

Serious events: 6 serious events

Other events: 9 other events

Deaths: 7 deaths

Cohort 3a

Serious events: 21 serious events

Other events: 50 other events

Deaths: 0 deaths

Cohort 3b

Serious events: 12 serious events

Other events: 33 other events

Deaths: 0 deaths

PK Sub-Study

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=29 participants at risk Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 2: BP-CML Only n=8 participants at risk Children and adolescents with BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 2: Ph + ALL Only n=9 participants at risk Children and adolescents with Ph+ ALL who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 participants at risk Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 participants at risk Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	PK Sub-Study n=7 participants at risk Children and adolescents received powder for oral suspension (PFOS) at a dose of 90 mg/m2 QD to evaluate the pharmacokinetics of dasatinib.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Anaemia	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 3/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Leukopenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Neutropenia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Cardiac disorders Left ventricular dysfunction	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Cardiac disorders Pericardial effusion	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Ear and labyrinth disorders Vertigo	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Anal ulcer	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Colitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Diarrhoea	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Enteritis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Haematochezia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Pancreatitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Stomatitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Vomiting	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Chills	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Fatigue	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Oedema peripheral	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Pain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Pyrexia	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Hepatobiliary disorders Hepatic function abnormal	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Immune system disorders Drug hypersensitivity	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Adenovirus infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations COVID-19	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Cellulitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Device related infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Enterococcal sepsis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Enterocolitis infectious	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gastroenteritis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gastrointestinal infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Infection	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Large intestine infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Meningitis aseptic	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Myringitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Oral herpes	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Otitis externa	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Periorbital cellulitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Sepsis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Skin infection	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Upper aerodigestive tract infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Upper respiratory tract infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Viral pericarditis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Craniofacial fracture	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Overdose	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Alanine aminotransferase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Aspartate aminotransferase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood creatine phosphokinase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations White blood cell count decreased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Dehydration	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia recurrent	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blast cell crisis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia transformation	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia recurrent	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Arachnoiditis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Depressed level of consciousness	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Facial nerve disorder	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Headache	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Presyncope	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Seizure	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Syncope	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Confusional state	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Personality change	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Suicidal ideation	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Renal and urinary disorders Acute kidney injury	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Renal and urinary disorders Ischaemic nephropathy	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Genital haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Chylothorax	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Cough	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Lung disorder	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Pleurisy	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Jugular vein thrombosis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.

Other adverse events

Other adverse events
Measure	Cohort 1 n=29 participants at risk Children and adolescents with CP-CML who were resistant or intolerant to imatinib received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 2: BP-CML Only n=8 participants at risk Children and adolescents with BP-CML who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 2: Ph + ALL Only n=9 participants at risk Children and adolescents with Ph+ ALL who were resistant or intolerant to, or relapsed after imatinib therapy received dasatinib tablets at a dose schedule of 80 mg/m2 QD on a continuous oral regimen.	Cohort 3a n=51 participants at risk Children and adolescents with CP-CML who were treatment-naive received dasatinib tablets at 60 mg/m2 QD on a continuous oral regimen.	Cohort 3b n=33 participants at risk Children and adolescents with CP-CML who were treatment-naive received dasatinib powder for oral suspension (PFOS) at 72 mg/m2 QD on a continuous oral regimen.	PK Sub-Study n=7 participants at risk Children and adolescents received powder for oral suspension (PFOS) at a dose of 90 mg/m2 QD to evaluate the pharmacokinetics of dasatinib.
Vascular disorders Hypotension	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Haematoma	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Hot flush	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Anaemia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.6% 11/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.2% 7/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Haemoglobinaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Hypertension	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Leukopenia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	18.2% 6/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Neutropenia	20.7% 6/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	50.0% 4/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 3/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 17/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	24.2% 8/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Blood and lymphatic system disorders Thrombocytopenia	17.2% 5/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	50.0% 4/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	44.4% 4/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.5% 13/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	24.2% 8/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Cardiac disorders Palpitations	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Cardiac disorders Pericardial effusion	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Cardiac disorders Sinus bradycardia	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Ear and labyrinth disorders Ear pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.7% 8/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Ear and labyrinth disorders Hypoacusis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Endocrine disorders Hypothyroidism	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Eye disorders Dry eye	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Eye disorders Eye oedema	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Eye disorders Eye pain	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Eye disorders Periorbital oedema	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Eye disorders Vision blurred	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Abdominal pain	34.5% 10/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	35.3% 18/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	36.4% 12/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Abdominal pain upper	24.1% 7/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	23.5% 12/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	18.2% 6/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Anal fissure	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Anal ulcer	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Colitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Constipation	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.6% 11/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Dental caries	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Diarrhoea	58.6% 17/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.5% 3/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 3/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	56.9% 29/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	48.5% 16/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Dyspepsia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Flatulence	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Gastritis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.8% 6/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Gingival bleeding	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Mouth ulceration	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Nausea	37.9% 11/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.5% 3/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	43.1% 22/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	39.4% 13/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Oral pain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Stomatitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Tongue ulceration	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Toothache	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Gastrointestinal disorders Vomiting	55.2% 16/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.5% 3/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 3/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	43.1% 22/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	39.4% 13/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Asthenia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Chest discomfort	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Chest pain	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Chills	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Face oedema	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Fatigue	27.6% 8/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.6% 11/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	24.2% 8/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Influenza like illness	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Malaise	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Mass	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Mucosal inflammation	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Non-cardiac chest pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Oedema peripheral	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Pain	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.8% 6/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	18.2% 6/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Peripheral swelling	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Pyrexia	51.7% 15/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	55.6% 5/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	45.1% 23/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	42.4% 14/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
General disorders Swelling face	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Hepatobiliary disorders Hepatomegaly	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Immune system disorders Drug hypersensitivity	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Immune system disorders Hypersensitivity	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Abscess	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Bronchitis	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations COVID-19	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Cellulitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Conjunctivitis	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Ear infection	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Febrile infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Folliculitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gastroenteritis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.7% 8/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gastroenteritis viral	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gastrointestinal infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Gingivitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Herpes virus infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Hordeolum	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Influenza	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	17.6% 9/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Localised infection	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Lower respiratory tract infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Molluscum contagiosum	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Nasopharyngitis	27.6% 8/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	19.6% 10/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Oral herpes	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Otitis media	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Pharyngitis	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	22.2% 2/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	13.7% 7/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Pneumonia	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Respiratory tract infection	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Rhinitis	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.7% 8/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Sinusitis	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Skin infection	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Tonsillitis	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Tooth infection	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Upper respiratory tract infection	34.5% 10/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.3% 19/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	42.4% 14/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Urinary tract infection	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Infections and infestations Viral infection	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Arthropod bite	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Contusion	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Injury, poisoning and procedural complications Sunburn	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Alanine aminotransferase increased	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.5% 3/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	18.2% 6/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Aspartate aminotransferase increased	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood alkaline phosphatase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood creatinine increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood lactate dehydrogenase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood phosphorus decreased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Blood urea increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Gamma-glutamyltransferase increased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Haemoglobin decreased	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Neutrophil count decreased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	24.2% 8/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Platelet count decreased	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	36.4% 12/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Weight decreased	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations Weight increased	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Investigations White blood cell count decreased	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Decreased appetite	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Fluid retention	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hyperalbuminaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypocalcaemia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Metabolism and nutrition disorders Vitamin D deficiency	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Arthralgia	20.7% 6/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.5% 13/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	27.3% 9/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Back pain	17.2% 5/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	23.5% 12/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	24.2% 8/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Bone pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 3/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Muscle spasms	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Myalgia	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	18.2% 6/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Neck pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Pain in extremity	51.7% 15/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	25.0% 2/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.6% 11/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	45.5% 15/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Pain in jaw	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Musculoskeletal and connective tissue disorders Tendonitis	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Arachnoiditis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Brain oedema	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Dizziness	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	23.5% 12/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Dysgeusia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Facial paralysis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Headache	58.6% 17/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.5% 3/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	55.6% 5/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	49.0% 25/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	48.5% 16/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Neuropathy peripheral	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Paraesthesia	17.2% 5/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Nervous system disorders Somnolence	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Anxiety	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Depression	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Psychiatric disorders Insomnia	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Renal and urinary disorders Dysuria	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Renal and urinary disorders Urinary incontinence	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Breast mass	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Dysmenorrhoea	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Heavy menstrual bleeding	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Menstruation irregular	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Pelvic pain	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Cough	51.7% 15/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	44.4% 4/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.3% 19/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	36.4% 12/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.8% 5/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.7% 6/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	23.5% 12/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	33.3% 11/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.2% 5/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.3% 3/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	23.5% 12/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Acne	13.8% 4/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	21.2% 7/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Alopecia	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.8% 6/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Dermatitis acneiform	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Dermatitis atopic	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Dry skin	17.2% 5/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Eczema	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	6.1% 2/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Erythema	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Papule	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Petechiae	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.0% 1/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Pruritus	17.2% 5/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	15.7% 8/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Rash	31.0% 9/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	37.3% 19/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	42.4% 14/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	5.9% 3/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	9.1% 3/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	3.9% 2/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Skin exfoliation	3.4% 1/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Skin hypopigmentation	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	2.0% 1/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Skin induration	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	11.1% 1/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Urticaria	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	7.8% 4/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.1% 4/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Skin and subcutaneous tissue disorders Xeroderma	6.9% 2/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Phlebitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.
Vascular disorders Thrombophlebitis	0.00% 0/29 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	12.5% 1/8 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/9 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/51 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/33 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.	0.00% 0/7 • Participants were assessed for All-Cause Mortality, Serious adverse events (SAEs) and Other adverse events (AEs) in all treated participants (up to approximately 14 years 6 months). The participants who crossed over from Cohort 3 to PK Sub-study are accounted for in both arms. PK Sub-study only for the duration of the PK Sub-study.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER