Trial Outcomes & Findings for Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease (NCT NCT04218084)

NCT ID: NCT04218084

Last Updated: 2025-06-13

Results Overview

TAMMV was defined as the time averaged maximum of the mean velocity arterial cerebral blood flow and was measured using transcranial Doppler (TCD). Analysis was performed using mixed model for repeated measures (MMRM) including treatment, study visit, treatment by visit interaction, baseline hydroxyurea (HU) use (yes; no), age group (2 to \<= 8 years; \>8 to \<15 years), and baseline TAMMV value (170 centimeter per second \[cm/sec\] to \< 185 cm/sec; 185 cm/sec to \< 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-participant variability.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 236 participants
• Primary outcome timeframe: Baseline (value at screening), Week 24
• Results posted on: 2025-06-13

Participant Flow

A total of 236 participants were assigned to the study treatment. Results are presented for only primary outcome measure. Remaining outcome measures would be reported upon completion of their analysis at study completion date. Data cut-off date for this study was 18-Jan-2024.

Participant milestones

Measure	Voxelotor Participants aged greater than or equal to 12 years of age received 1500 milligrams (mg) voxelotor tablet orally once daily for 96 weeks. Participants less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose. Participants were followed up to 4 weeks after last dose of study drug.	Placebo Participants received voxelotor matched placebo orally once daily for 96 weeks. Participants were followed up to 4 weeks after last dose of study drug.
Overall Study STARTED	120	116
Overall Study COMPLETED	25	23
Overall Study NOT COMPLETED	95	93

Reasons for withdrawal

Measure	Voxelotor Participants aged greater than or equal to 12 years of age received 1500 milligrams (mg) voxelotor tablet orally once daily for 96 weeks. Participants less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose. Participants were followed up to 4 weeks after last dose of study drug.	Placebo Participants received voxelotor matched placebo orally once daily for 96 weeks. Participants were followed up to 4 weeks after last dose of study drug.
Overall Study Adverse Event	7	2
Overall Study Withdrawal of Consent	4	5
Overall Study Physician Decision	1	1
Overall Study Lost to Follow-up	1	1
Overall Study Non-compliance with study drug	1	1
Overall Study Abnormal transcranial doppler (TCD)	19	24
Overall Study Other	0	1
Overall Study Ongoing at data cut-off date	62	58

Baseline Characteristics

Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease

Baseline characteristics by cohort

Measure	Voxelotor n=120 Participants Participants aged greater than or equal to 12 years of age received 1500 mg voxelotor tablet orally once daily for 96 weeks. Participants less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose. Participants were followed up to 4 weeks after last dose of study drug.	Placebo n=116 Participants Participants received voxelotor matched placebo orally once daily for 96 weeks. Participants were followed up to 4 weeks after last dose of study drug.	Total n=236 Participants Total of all reporting groups
Age, Customized Age · 2 to less than (<) 4 Years	14 Participants n=93 Participants	10 Participants n=4 Participants	24 Participants n=27 Participants
Age, Customized Age · 4 to < 12 Years	91 Participants n=93 Participants	92 Participants n=4 Participants	183 Participants n=27 Participants
Age, Customized Age · 12 to < 15 Years	15 Participants n=93 Participants	14 Participants n=4 Participants	29 Participants n=27 Participants
Sex: Female, Male Sex · Female	63 Participants n=93 Participants	59 Participants n=4 Participants	122 Participants n=27 Participants
Sex: Female, Male Sex · Male	57 Participants n=93 Participants	57 Participants n=4 Participants	114 Participants n=27 Participants
Ethnicity (NIH/OMB) Ethnicity · Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Ethnicity · Not Hispanic or Latino	114 Participants n=93 Participants	113 Participants n=4 Participants	227 Participants n=27 Participants
Ethnicity (NIH/OMB) Ethnicity · Unknown or Not Reported	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Race/Ethnicity, Customized Race · African	69 Participants n=93 Participants	80 Participants n=4 Participants	149 Participants n=27 Participants
Race/Ethnicity, Customized Race · Arab	12 Participants n=93 Participants	11 Participants n=4 Participants	23 Participants n=27 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=93 Participants	2 Participants n=4 Participants	10 Participants n=27 Participants
Race/Ethnicity, Customized Race · White	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Race · Multi-Racial	29 Participants n=93 Participants	23 Participants n=4 Participants	52 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (value at screening), Week 24

Population: ITT analysis population included all randomized participants. Here, "Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure.

TAMMV was defined as the time averaged maximum of the mean velocity arterial cerebral blood flow and was measured using transcranial Doppler (TCD). Analysis was performed using mixed model for repeated measures (MMRM) including treatment, study visit, treatment by visit interaction, baseline hydroxyurea (HU) use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-participant variability.

Outcome measures

Measure	Voxelotor n=108 Participants Participants aged 12 years or older were received 1500 milligrams (mg) voxelotor orally once daily for 96 weeks. Participants aged 2 to less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose.	Placebo n=114 Participants Participants received voxelotor matched placebo orally once daily for 96 weeks.
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	-12.15 Centimeter per second (cm/sec) Interval -15.83 to -8.46	-4.42 Centimeter per second (cm/sec) Interval -8.23 to -0.61

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Change in TCD flow velocity from baseline to week 48 was analyzed using the MMRM model including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 cm/sec to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-subject variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Time to conversion was the number of weeks from the date of randomization to the date of TCD assessment when an abnormal TCD flow velocity (>= 200 cm/sec) is determined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Time to first normal TCD flow was the number of weeks from randomization to the date of first normal (<170 cm/sec) TCD flow.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

TCD flow velocity reduction from Baseline ≥ 15 cm/sec at week 24, week 48 was analyzed using an exact Cochran-Mantel-Haenszel (CMH) general association test stratified for baseline HU use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 cm/sec to < 185 cm/sec; 185 cm/sec to < 200 cm/sec).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Change from baseline in hemoglobin at weeks 24 and 48 was analyzed using the MMRM model including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years) and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-participant variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Percent change from baseline in unconjugated bilirubin at weeks 24 and 48 was reported in this outcome measure. Analysis was performed using MMRM including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-subject variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Percent change from baseline in reticulocyte at weeks 24 and 48 was reported in this outcome measure. Analysis was performed using MMRM including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-participant variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Percent change from baseline in absolute reticulocyte at weeks 24 and 48 was reported in this outcome measure. Analysis was performed using MMRM including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-subject variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

Percent change from baseline in LDH at weeks 24 and 48 was reported in this outcome measure. Analysis was performed using MMRM including treatment, study visit, treatment by visit interaction, baseline hydroxyurea use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 centimeter per second [cm/sec] to < 185 cm/sec; 185 cm/sec to < 200 cm/sec) as fixed effect terms and used a compound symmetry covariance matrix for within-subject variability.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation till study completion

VOC was defined as a composite of acute painful crisis and/or acute chest syndrome (ACS). Annualized incidence rate was defined as total number of events per total person-years. Total person-years was the sum of participants treatment period in years, which included the time from randomization date to the earliest of (last dose date, post-randomization initiation for participants with no hydroxyurea at baseline, end of study, and data cutoff date). The 95% CI of rate displayed the exact Poisson confidence limits.

Outcome measures

Outcome data not reported

Adverse Events

Voxelotor

Serious events: 48 serious events

Other events: 40 other events

Deaths: 6 deaths

Placebo

Serious events: 24 serious events

Other events: 27 other events

Deaths: 2 deaths

Serious adverse events

Measure	Voxelotor n=120 participants at risk Participants aged greater than or equal to 12 years of age received 1500 mg voxelotor tablet orally once daily for 96 weeks. Participants less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose. Participants were followed up to 4 weeks after last dose of study drug.	Placebo n=116 participants at risk Participants received voxelotor matched placebo orally once daily for 96 weeks.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	35.0% 42/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.4% 19/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Anaemia	8.3% 10/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.8% 9/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Haemolytic anaemia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Leukocytosis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Neutropenia	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Acute chest syndrome	6.7% 8/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.9% 8/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pneumonia	5.0% 6/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pneumonia viral	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Malaria	15.0% 18/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	11.2% 13/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Sepsis	7.5% 9/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.4% 4/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Cellulitis	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Gastroenteritis	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Arthritis bacterial	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Bronchitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Diphtheria	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Meningitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Osteomyelitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Osteomyelitis chronic	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pharyngitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Septic shock	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Tonsillitis	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Urinary tract infection	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pyrexia	15.0% 18/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.3% 5/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain	4.2% 5/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Diarrhoea	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Vomiting	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Seizure	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Cerebrovascular accident	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Haemorrhagic stroke	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Angina pectoris	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Cardiac failure	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Coronary artery thrombosis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Cholecystitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hepatomegaly	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hyperbilirubinaemia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Congenital, familial and genetic disorders Eyelid ptosis congenital	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Eye disorders Periorbital oedema	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Liver function test abnormal	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Glomerulonephritis acute	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders Hypertensive emergency	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Other adverse events

Measure	Voxelotor n=120 participants at risk Participants aged greater than or equal to 12 years of age received 1500 mg voxelotor tablet orally once daily for 96 weeks. Participants less than 12 years of age received voxelotor at a weight based (1500 mg-equivalent) dose. Participants were followed up to 4 weeks after last dose of study drug.	Placebo n=116 participants at risk Participants received voxelotor matched placebo orally once daily for 96 weeks.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	33.3% 40/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	23.3% 27/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Anaemia	3.3% 4/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.2% 6/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Thrombocytosis	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Leukocytosis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Neutropenia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Neutrophilia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Splenomegaly	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Haemolysis	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Leukopenia	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pneumonia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Malaria	10.8% 13/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	11.2% 13/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	8.3% 10/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.0% 7/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Tonsillitis	4.2% 5/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.3% 5/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Bronchitis	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Nasopharyngitis	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.4% 4/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pharyngotonsillitis	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Respiratory tract infection	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.2% 6/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pharyngitis	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Sepsis	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Varicella	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Bacterial infection	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Body tinea	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations COVID-19	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Conjunctivitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Escherichia urinary tract infection	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Metapneumovirus infection	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Mumps	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Osteomyelitis acute	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Parotitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Rash pustular	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Viral upper respiratory tract infection	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Carbuncle	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Cellulitis	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Gastroenteritis	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.4% 4/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Urinary tract infection	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 6/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 5/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Back pain	3.3% 4/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Bone pain	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Acute chest syndrome	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 12/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	3.3% 4/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Productive cough	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pyrexia	12.5% 15/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.6% 10/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Chest pain	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Gait disturbance	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Non-cardiac chest pain	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pain	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Fatigue	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Influenza like illness	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain	5.8% 7/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.3% 5/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Diarrhoea	4.2% 5/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Vomiting	4.2% 5/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.4% 4/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Dyspepsia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Mouth ulceration	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Alanine aminotransferase increased	3.3% 4/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood bilirubin increased	3.3% 4/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Aspartate aminotransferase increased	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood lactate dehydrogenase increased	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Cardiac murmur	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Hepatic enzyme increased	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Urine albumin/creatinine ratio increased	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Bilirubin conjugated increased	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood albumin decreased	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Heart rate irregular	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Platelet count increased	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Vitamin D decreased	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Ocular icterus	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hepatomegaly	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hepatosplenomegaly	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hyperbilirubinaemia	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Jaundice	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.4% 4/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	5.0% 6/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Dizziness	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.7% 2/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Seizure	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Dermatitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Macule	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Pruritus	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash macular	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash papular	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Urticaria	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Bone fissure	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Soft tissue injury	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Wound	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Nail injury	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Overdose	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hyperkalaemia	1.7% 2/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.6% 3/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders Pallor	2.5% 3/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders Hypertension	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Eye disorders Night blindness	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Eye disorders Vernal keratoconjunctivitis	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Eye disorders Eye pruritus	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Eye disorders Ocular hyperaemia	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Cardiac failure congestive	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Right ventricular failure	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Ear and labyrinth disorders Motion sickness	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Immune system disorders Hypersensitivity	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Anxiety	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Pollakiuria	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Sickle cell nephropathy	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.86% 1/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Direct Billirubin	0.83% 1/120 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/116 • From Day 1 up to 28 days after last dose of study drug (maximum treatment exposure was 106 weeks) Same event may appear as both SAE and non-SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER