Trial Outcomes & Findings for An Open Label Pharmacokinetic, Safety And Efficacy Study Of Maraviroc In Combination With Background Therapy For The Treatment Of HIV-1 Infected, CCR5 -Tropic Children (NCT NCT00791700)

Last Updated: 2020-04-28

Results Overview

Cavg: calculated as area under the curve divided by a dosing interval of 12 hours. Cmin: directly observed plasma concentration prior to the next dose. Geometric Coefficient of Variation is defined as the geometric standard deviation to the power of the reciprocal of the geometric mean.

Recruitment status

UNKNOWN

Study phase

PHASE2

Target enrollment

103 participants

Primary outcome timeframe

Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Results posted on

2020-04-28

Participant Flow

This open-label, multicenter, multiple dose pharmacokinetic, safety and efficacy study at 24 sites in 8 countries.

The participants were HIV-1 infected treatment-experienced children and adolescents who were failing current antiretroviral (ARV) therapy or have failed their most recent ARV regimen, defined by plasma HIV-1 RNA\>=1000 copies/mL, were infected with only R5 HIV-1, and have ARV experience/intolerance of 6 months with at least 2 ARV drug classes.

Participant milestones

Participant milestones
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 milligram per milliliter \[mg/mL\]).	>=6 - <12 Years of Age, MVC Tablet Formulation In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 milligram \[mg\], 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Overall Study STARTED	16	31	13	43
Overall Study COMPLETED	10	20	7	13
Overall Study NOT COMPLETED	6	11	6	30

Reasons for withdrawal

Reasons for withdrawal
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 milligram per milliliter \[mg/mL\]).	>=6 - <12 Years of Age, MVC Tablet Formulation In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 milligram \[mg\], 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Overall Study Insufficient clinical response	1	4	1	8
Overall Study No longer willing to participate	1	1	0	8
Overall Study Non-compliance with study treatment	0	2	0	4
Overall Study Withdrawn due to pregnancy	0	0	0	1
Overall Study Other	0	1	0	1
Overall Study Death	0	0	0	1
Overall Study Lost to Follow-up	4	3	4	6
Overall Study Adverse Event	0	0	1	1

Baseline Characteristics

An Open Label Pharmacokinetic, Safety And Efficacy Study Of Maraviroc In Combination With Background Therapy For The Treatment Of HIV-1 Infected, CCR5 -Tropic Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Total n=103 Participants Total of all reporting groups
Age, Continuous	3.4 Years STANDARD_DEVIATION 0.9 • n=5 Participants	9.1 Years STANDARD_DEVIATION 1.7 • n=7 Participants	8.9 Years STANDARD_DEVIATION 2.0 • n=5 Participants	14.0 Years STANDARD_DEVIATION 1.6 • n=4 Participants	10.3 Years STANDARD_DEVIATION 4.1 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	16 Participants n=7 Participants	6 Participants n=5 Participants	27 Participants n=4 Participants	54 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	15 Participants n=7 Participants	7 Participants n=5 Participants	16 Participants n=4 Participants	49 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Population: PK analysis set consisted of all enrolled participants who had at least one PK sample with a dosing history. "Number analyzed": participants evaluable at specified time points for this measure.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=11 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=10 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=17 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cmax-Week 48	334.68 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 156	593.68 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 25	284.96 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 128	423.32 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 48	—	—	—	—
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cmin-Week2	18.97 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 202208	100.02 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 39	115.84 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 90	56.17 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 145	—	—	—	—
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cavg-Week2	237.34 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 63	260.65 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 43	264.45 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 62	239.85 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 67	—	—	—	—
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cavg-Week 48	163.73 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 146	289.69 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 50	168.62 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 117	199.12 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 78	—	—	—	—
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cmax-Week2	581.47 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 69	546.80 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 51	444.37 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 61	530.80 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 62	—	—	—	—
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) Cmin-Week 48	48.11 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 180	82.21 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 120	60.03 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 245	66.51 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 140	—	—	—	—

PRIMARY outcome

Timeframe: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Population: PK analysis set consisted of all enrolled participants who had at least one PK sample with a dosing history. "Number analyzed" signifies participants evaluable at specified time points for this outcome measure.

AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 12 hours.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=11 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=10 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=17 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Area Under the Curve at Steady State (AUCtau) AUCtau - Week 2	2848.1 ng*hr/mL Geometric Coefficient of Variation 63	3127.7 ng*hr/mL Geometric Coefficient of Variation 43	3173.4 ng*hr/mL Geometric Coefficient of Variation 62	2878.2 ng*hr/mL Geometric Coefficient of Variation 67	—	—	—	—
Area Under the Curve at Steady State (AUCtau) AUCtau - Week 48	1964.7 ng*hr/mL Geometric Coefficient of Variation 146	3476.3 ng*hr/mL Geometric Coefficient of Variation 50	2023.5 ng*hr/mL Geometric Coefficient of Variation 117	2389.4 ng*hr/mL Geometric Coefficient of Variation 78	—	—	—	—

PRIMARY outcome

Timeframe: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=11 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=10 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=17 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Time to Reach Maximum Plasma Concentration (Tmax) Tmax - Week 2	2.000 hour Interval 0.97 to 6.0	4.000 hour Interval 0.75 to 6.0	2.000 hour Interval 1.0 to 4.0	2.000 hour Interval 1.0 to 4.0	—	—	—	—
Time to Reach Maximum Plasma Concentration (Tmax) Tmax - Week 48	2.000 hour Interval 0.0 to 6.03	2.000 hour Interval 1.0 to 8.0	3.000 hour Interval 0.0 to 6.0	2.000 hour Interval 1.0 to 4.0	—	—	—	—

PRIMARY outcome

Timeframe: Baseline up to 5 years

Population: Safety analysis was performed on all participants who received at least 1 dose of study drug.

Incidence is reported in terms of number of events of AEs. The investigator used the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1= Symptoms causing no or minimal interference with usual social and functional activities; Grade 2= Symptoms causing greater than minimal interference with usual social and functional activities; Grade 3= Symptoms causing inability to perform usual social and functional activities; Grade 4= Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data have been reported in the measure for Grade 3 and 4 as per system organ class and preferred term.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=16 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=31 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 3) n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Gastrointestinal disorders - Vomiting	1 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Hepat. disorders - Drug-induced liver injury	0 events	0 events	0 events	0 events	0 events	1 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Infections and infestations - H1N1 influenza	0 events	0 events	0 events	0 events	1 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Infections and infestations - Pneumonia	0 events	0 events	0 events	1 events	1 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Investigations - Lipase increased	0 events	1 events	0 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Pyschiatric disorder - Bipolar disorder	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Gastrointestinal disorders - Gastritis	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Investigations - Hepatic enzyme abnormal	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Infections and infestations -Otitis media	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Investigations - Transaminases increased	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Pyschiatric disorder - Aggression	0 events	0 events	1 events	0 events	0 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Blood and lymphatic system disorders - Anaemia	0 events	0 events	0 events	0 events	1 events	0 events
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality) Infections and infestations - Meningitis	0 events	0 events	0 events	0 events	0 events	1 events

PRIMARY outcome

Timeframe: Baseline up to 5 years

Population: Safety analysis was performed on all participants who received at least 1 dose of study drug.

The primary reason for a participant discontinuing from study drug or the clinical study was recorded in the source documents as well as the case report form. A discontinuation had to be reported immediately to the study medical monitor or his/her designated representative if it was due to an SAE and was considered as a secondary reason.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Treatment Discontinuation: Secondary Reasons- Serious Adverse Event (SAE) Related to Study Drug	0 participants	0 participants	0 participants	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Week 24 and Week 48 post-treatment

Population: The FAS consisted of all participants who receive at least one dose of study medication.

The proportion of participants who achieved HIV-1 RNA \<400 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach Week 24	68.8 percentage of participants	90.3 percentage of participants	69.2 percentage of participants	62.8 percentage of participants	—	—	—	—
Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach Week 48	75.0 percentage of participants	77.4 percentage of participants	69.2 percentage of participants	51.2 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Week 24 and Week 48 post-treatment

Population: The FAS consisted of all participants who received at least 1 dose of study drug.

The proportion of participants who achieved HIV-1 RNA \<48 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With HIV-1 RNA <48 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F)Approach Week 24	18.75 percentage of participants	64.5 percentage of participants	61.5 percentage of participants	48.8 percentage of participants	—	—	—	—
Percentage of Participants With HIV-1 RNA <48 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F)Approach Week 48	50.0 percentage of participants	54.8 percentage of participants	53.8 percentage of participants	39.5 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Week 24 and Week 48 post-treatment

Population: The FAS consisted of all participants who received at least 1 dose of study drug. "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this measure."Number analyzed" signifies participants evaluable at specified time points for this outcome measure.

Participants who have been discontinued from the study, have been lost to follow-up, or have missing HIV-1 RNA data prior to the time point of interest were considered to have HIV-1 RNA levels \> lower limit of quantification (LLOQ) . This referred to as \[non-completer = failure; NC=F\] or \[missing, discontinuation = failure; MD=F\].

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=27 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=9 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=27 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach Week 24	62.5 Percentage of participants Interval 38.8 to 86.2	87.10 Percentage of participants Interval 75.3 to 98.9	69.2 Percentage of participants Interval 44.1 to 94.3	62.8 Percentage of participants Interval 48.3 to 77.2	—	—	—	—
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach Week 48	75.0 Percentage of participants Interval 53.8 to 96.2	74.2 Percentage of participants Interval 58.8 to 89.6	69.2 Percentage of participants Interval 44.1 to 94.3	51.2 Percentage of participants Interval 36.2 to 66.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 24 and Week 48 post-treatment

Participants who have been discontinued from the study, have been lost to follow-up, or have missing HIV-1 RNA data prior to the time point of interest were considered to have HIV-1 RNA levels \> lower limit of quantification (LLOQ) . This referred as \[non-completer = failure; NC=F\] or \[missing, discontinuation = failure; MD=F\].

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=8 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=20 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=8 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=21 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach Week 24	18.8 Percentage of participants Interval 0.0 to 37.9	64.5 Percentage of participants Interval 47.7 to 81.4	61.5 Percentage of participants Interval 35.1 to 89.0	48.8 Percentage of participants Interval 33.9 to 63.8	—	—	—	—
Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach Week 48	50.0 Percentage of participants Interval 25.5 to 74.5	54.8 Percentage of participants Interval 34.0 to 69.2	53.8 Percentage of participants Interval 35.1 to 89.0	39.5 Percentage of participants Interval 24.9 to 54.2	—	—	—	—

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all participants who received at least 1 dose of study drug.

TLOVR is defined as the time from first dose of study medication (Day 1) until the time of virologic failure using the a TLOVR algorithm.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With HIV-1 RNA <400 Copies/mL and <48 Copies/mL Using the Time to Loss of Virologic Response Algorithm (TLOVR) at Week 48 <400 copies/mL; TLOVR Responder	62.5 Percentage of participants	74.2 Percentage of participants	69.2 Percentage of participants	48.8 Percentage of participants	—	—	—	—
Percentage of Participants With HIV-1 RNA <400 Copies/mL and <48 Copies/mL Using the Time to Loss of Virologic Response Algorithm (TLOVR) at Week 48 <48 copies/mL; TLOVR Responder	43.8 Percentage of participants	54.8 Percentage of participants	46.2 Percentage of participants	44.2 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 24, Week 48 post-treatment

Population: The FAS consisted of all participants who received at least 1 dose of study drug. Last Observation Carried Forward (LOCF) was used to impute missing values.

Percentage of participants with at least a 1.0 log10 reduction in HIV-1 RNA from baseline to Week 24 and Week 48 were tabulated.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48 Baseline to Week 24	92.3 percentage of participants Interval 77.8 to 106.8	100.0 percentage of participants Interval 100.0 to 100.0	100.0 percentage of participants Interval 100.0 to 100.0	93.1 percentage of participants Interval 83.9 to 102.3	—	—	—	—
Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48 Baseline to Week 48	100.0 percentage of participants Interval 100.0 to 100.0	96.2 percentage of participants Interval 88.8 to 103.6	100.0 percentage of participants Interval 100.0 to 100.0	88.0 percentage of participants Interval 75.3 to 100.7	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48 post-treatment

Population: The FAS consisted of all participants who received at least 1 dose of study drug. LOCF was used to impute missing values. "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Plasma HIV-1 RNA was determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (lower limit of quantification \[LLOQ\] \<48 copies/mL). Blood samples were taken at the time points indicated in the participant evaluation schedule. Screening HIV-1 RNA \>1000 copies/ml was used to determine eligibility for the study.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=15 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=39 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Change From Baseline in HIV-1 RNA (Original) Change from Baseline - Original - Week 24	-271974.6 copies/mL Standard Deviation 391843.59	-38764.0 copies/mL Standard Deviation 63688.93	-58081.0 copies/mL Standard Deviation 79720.33	-57325.7 copies/mL Standard Deviation 172108.62	—	—	—	—
Change From Baseline in HIV-1 RNA (Original) Change from Baseline - Original - Week 48	-267834.2 copies/mL Standard Deviation 378896.88	-34787.7 copies/mL Standard Deviation 60222.60	-56351.7 copies/mL Standard Deviation 76231.03	-55321.1 copies/mL Standard Deviation 173840.55	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48 post-treatment

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=15 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=39 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Change From Baseline in HIV-1 RNA (Log10 Copies/mL) Change from Baseline - Log10 - Week 24	-2.4853 Log10 Copies/mL Standard Deviation 1.1421	-2.2324 Log10 Copies/mL Standard Deviation 0.8668	-2.1756 Log10 Copies/mL Standard Deviation 1.1854	-1.6482 Log10 Copies/mL Standard Deviation 1.3806	—	—	—	—
Change From Baseline in HIV-1 RNA (Log10 Copies/mL) Change from Baseline - Log10 - Week 48	-2.5831 Log10 Copies/mL Standard Deviation 1.2148	-1.9579 Log10 Copies/mL Standard Deviation 1.0861	-2.0549 Log10 Copies/mL Standard Deviation 1.2125	-1.4591 Log10 Copies/mL Standard Deviation 1.4477	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48 post-treatment

Change from baseline in CD4 cell count to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=15 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=30 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=39 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48 Week 24	232.7 cells/mm^3 Standard Deviation 381.6	355.8 cells/mm^3 Standard Deviation 294.0	213.9 cells/mm^3 Standard Deviation 166.4	173.6 cells/mm^3 Standard Deviation 203.6	—	—	—	—
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48 Week 48	275.9 cells/mm^3 Standard Deviation 363.4	362.7 cells/mm^3 Standard Deviation 373.5	167.3 cells/mm^3 Standard Deviation 150.9	168.6 cells/mm^3 Standard Deviation 211.0	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24 and Week 48 post-treatment

Change from baseline in CD4 % to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=15 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=12 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=39 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Change From Baseline in Percentage (%) of CD4+ Cells at Weeks 24 and 48 Week 48	7.5 percentage of CD4+ cells Standard Deviation 7.6	6.0 percentage of CD4+ cells Standard Deviation 6.8	2.5 percentage of CD4+ cells Standard Deviation 4.2	4.6 percentage of CD4+ cells Standard Deviation 6.5	—	—	—	—
Change From Baseline in Percentage (%) of CD4+ Cells at Weeks 24 and 48 Week 24	7.3 percentage of CD4+ cells Standard Deviation 5.0	3.8 percentage of CD4+ cells Standard Deviation 7.4	3.5 percentage of CD4+ cells Standard Deviation 4.0	3.8 percentage of CD4+ cells Standard Deviation 6.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 48

Population: The FAS consisted of all participants who received at least 1 dose of study drug.

The occurrence of any one of the following criteria would constitute Virologic failure: Criteria A=Decrease from Baseline plasma HIV-1 RNA \<1 log10 and plasma HIV-1 RNA \>400 copies/mL starting at Week 12 and confirmed at consecutive Week 16; Criteria B=Decrease from Baseline plasma HIV-1 RNA \<2.0 log10 and plasma HIV-1 RNA \>400 copies/mL at Week 24 OR plasma HIV-1 RNA \>10,000 copies/mL on and after Week 24, and confirmed within 14 to 21 days; Criteria C=Increase from nadir plasma HIV-1 RNA of \>=1 log10 (\>=1,000 copies/mL if nadir plasma HIV-1 RNA \<48 copies/mL) at any time, and confirmed within 14 to 21 days.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Number of Participants With Protocol Defined Virologic Failure Criteria A	0 participants	2 participants	1 participants	5 participants	—	—	—	—
Number of Participants With Protocol Defined Virologic Failure Criteria B	0 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Protocol Defined Virologic Failure Criteria C	3 participants	3 participants	2 participants	8 participants	—	—	—	—

SECONDARY outcome

Timeframe: Screening to Week 48

Population: Participants who experienced confirmed PDVF through Week 48 with sufficient plasma HIV-1 RNA for virology analysis while receiving MVC. One participant was excluded from summary tables as classified as MSDF response; one participant was analyzed after stopping treatment.

Virus tropism was determined using the Monogram Biosciences Trofile™ viral tropism assay. Change in detected tropism from screening to the time of failure prior to Week 48 was reported. X4=CXCR4 tropic virus; R5=CCR5-tropic virus; X4=CXCR4-tropic virus. Number of participants as per tropism to respective virus has been reported.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=3 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=4 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=3 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=13 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 With valid on-treatment results	2 participants	4 participants	3 participants	11 participants	—	—	—	—
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 Tropism at Confirmed PDVF R5	2 participants	3 participants	2 participants	9 participants	—	—	—	—
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 Tropism at Confirmed PDVF DM	0 participants	1 participants	1 participants	2 participants	—	—	—	—
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 Tropism at Confirmed PDVF X4	0 participants	0 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 Tropism at Confirmed PDVF Not Reportable	1 participants	0 participants	0 participants	1 participants	—	—	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: The FAS consisted of all participants who received at least 1 dose of study drug. "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Phenotypic and genotypic susceptibility to reverse transcriptase and protease inhibitors was evaluated at screening using the Monogram Biosciences PhenoSense™ GT (PSGT) assay. Samples from a confirmatory PDVF visit or early termination of MVC were planned to be analyzed if the plasma HIV-1 RNA was ≥400 copies/mL. Data for participants with respective gene mutation category has been reported. Participants with more than one mutation are counted more than once.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=3 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=4 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=3 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=13 Participants In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF PI Minor V77V/I	0 participants	0 participants	0 participants	1 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF NNRTI K103K/N	0 participants	1 participants	0 participants	0 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF PI Minor L10L/F	0 participants	0 participants	0 participants	1 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF NNRTI K103N	0 participants	0 participants	1 participants	1 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF With valid on-treatment results	2 participants	4 participants	3 participants	11 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF PI Minor L89L/I/M	0 participants	0 participants	0 participants	1 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF NRTI M184V	0 participants	0 participants	1 participants	0 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF PI Minor K20K/R	0 participants	0 participants	2 participants	0 participants	—	—	—	—
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF Total with emergence	0 participants	1 participants	3 participants	4 participants	—	—	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: The FAS consisted of all participants who received at least 1 dose of study drug.

Data was summarized by the total ARV activity of the background regimen using simple and weighted total optimized background treatment susceptibility scores as well as by screening genotype. Simple total optimized background treatment (OBT) susceptibility scores were categorized as 0, 1, \>=2 and weighted total OBT susceptibility scores were categorized as 0 to 0.5, 1 to 1.5 and \>=2. However, net susceptibility scores were imputed for simple analysis based on genotype. Susceptibility scores indicate the level resistance to the study medication. Scores ranged from 0 to 1 as 1 = susceptible and potential low-level resistance; 0.5 = low and intermediate-level resistance; 0 = high-level resistance, where higher scores indicated lower resistance.

Outcome measures

Outcome measures
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=49 Participants In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=23 Participants In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=31 Participants In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 3 (Grade 3) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 3 (Grade 4) In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	Cohort 4 (Grade 3) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	Cohort 4 (Grade 4) In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Simple score 0	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	—	—	—	—	—
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Simple score 1.0	8.2 Percentage of participants	4.3 Percentage of participants	0 Percentage of participants	—	—	—	—	—
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Simple score >=2.0	81.6 Percentage of participants	95.7 Percentage of participants	96.8 Percentage of participants	—	—	—	—	—
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Weighted score 0-0.5	6.1 Percentage of participants	30.4 Percentage of participants	29.0 Percentage of participants	—	—	—	—	—
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Weighted score 1.0-1.5	53.1 Percentage of participants	65.2 Percentage of participants	29.0 Percentage of participants	—	—	—	—	—
Percentage of Participants With Optimized Background Treatment Susceptibility Scores Weighted score >=2.0	28.6 Percentage of participants	4.3 Percentage of participants	38.7 Percentage of participants	—	—	—	—	—

Adverse Events

>=2 - <6 Years of Age, MVC Liquid Formulation

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

>=6 - <12 Years of Age, MVC Tablet Formulation

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

>=6 - <12 Years of Age, MVC Liquid Formulation

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

>=12 - <18 Years of Age, MVC Tablet Formulation

Serious events: 10 serious events

Other events: 34 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor 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 participating sites. Investigator may not disclose previously undisclosed confidential other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 participants at risk In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 participants at risk In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 participants at risk In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 participants at risk In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Blood and lymphatic system disorders Anaemia	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Gastric fistula	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Gastritis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Drug-induced liver injury	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Abscess oral	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 H1N1 influenza	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Pelvic inflammatory disease	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.7% 2/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Pulmonary tuberculosis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tooth abscess	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 infection	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Transaminases increased	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Osteopenia	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tendon disorder	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Bipolar disorder	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Hyperventilation	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Prurigo	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Otorrhoea	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Constipation	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	>=2 - <6 Years of Age, MVC Liquid Formulation n=16 participants at risk In Cohort 1, Participants aged \>= 2 to \< 6 years, received MVC liquid formulation (20 mg/mL).	>=6 - <12 Years of Age, MVC Tablet Formulation n=31 participants at risk In Cohort 2, Participants aged \>=6 to \<12 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).	>=6 - <12 Years of Age, MVC Liquid Formulation n=13 participants at risk In Cohort 3, Participants aged \>=6 to \<12 years, received MVC liquid formulation (20 mg/mL).	>=12 - <18 Years of Age, MVC Tablet Formulation n=43 participants at risk In Cohort 4, Participants aged \>=12 to \<18 years, received MVC tablet formulation (25 mg, 75 mg, 150 mg).
Infections and infestations Sinobronchitis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Sinusitis	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tinea capitis	12.5% 2/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tinea faciei	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tinea infection	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.7% 2/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tooth abscess	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tracheitis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tuberculosis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 allergic	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 contact	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.0% 3/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Iron deficiency anaemia	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Lymphadenitis	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	11.6% 5/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 disorder	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Deafness	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Conjunctival pallor	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Conjunctivitis allergic	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Hypermetropia	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Refraction disorder	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 discomfort	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	15.4% 2/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.3% 4/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 lower	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Anal pruritus	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Constipation	12.5% 2/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.7% 2/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Dental caries	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	43.8% 7/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	30.8% 4/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.9% 9/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Flatulence	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Gingival swelling	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	6.2% 1/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.7% 1/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Nausea	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	11.6% 5/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Odynophagia	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Proctitis	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Salivary gland mucocoele	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Tongue disorder	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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 Toothache	0.00% 0/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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% 0/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.3% 1/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one 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	37.5% 6/16 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.8% 8/31 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	23.1% 3/13 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.3% 4/43 • Baseline up to 5 years The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.