Trial Outcomes & Findings for Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079) (NCT NCT03379506)

NCT ID: NCT03379506

Last Updated: 2023-05-31

Results Overview

The AUC0-24hr of EBR at steady state (Week 4) was determined in each cohort.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Results posted on

2023-05-31

Participant Flow

Male and female participants 3 to \<18 years of age with chronic hepatitis C virus (HCV) genotype 1 (GT1) or GT4 were enrolled at 14 global study sites.

Participant milestones

Participant milestones
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded Pediatric participants 12 to \<18 years of age received elbasvir (EBR) 50 mg / grazoprevir (GZR) 100 mg fixed dose combination (FDC) tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Overall Study STARTED	22	17	7	11
Overall Study COMPLETED	22	17	7	11
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.	Total n=57 Participants Total of all reporting groups
Age, Continuous	14.1 Years STANDARD_DEVIATION 1.9 • n=5 Participants	8.7 Years STANDARD_DEVIATION 1.2 • n=7 Participants	3.7 Years STANDARD_DEVIATION 0.8 • n=5 Participants	4.8 Years STANDARD_DEVIATION 1.3 • n=4 Participants	9.4 Years STANDARD_DEVIATION 4.4 • n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	29 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	28 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	14 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants	50 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	17 Participants n=7 Participants	7 Participants n=5 Participants	11 Participants n=4 Participants	56 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Population: All randomized and treated participants who complied with the protocol sufficiently to ensure that their pharmacokinetic (PK) data was likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

The AUC0-24hr of EBR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State	2.41 µM*hr Interval 1.97 to 2.94	2.79 µM*hr Interval 2.31 to 3.37	1.71 µM*hr Interval 1.36 to 2.15	3.15 µM*hr Interval 2.52 to 3.96

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Population: All randomized and treated participants who complied with the protocol sufficiently to ensure that their PK data was likely to exhibit the effects of treatment, according to the underlying scientific model, are included.

The Cmax of EBR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Maximum Plasma Concentration (Cmax) of EBR	0.19 µM Interval 0.15 to 0.23	0.21 µM Interval 0.17 to 0.25	0.14 µM Interval 0.11 to 0.19	0.28 µM Interval 0.22 to 0.36

PRIMARY outcome

Timeframe: Week 4: Predose

The Ctrough of EBR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=16 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Steady State Predose Drug Concentration (Ctrough) of EBR	59.76 nM Interval 47.2 to 75.67	59.43 nM Interval 48.67 to 72.58	34.61 nM Interval 28.0 to 42.77	68.92 nM Interval 54.32 to 87.44

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

The CL/F of EBR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Apparent Clearance (CL/F) of EBR at Steady State	23.53 L/hr Interval 19.25 to 28.75	12.21 L/hr Interval 10.1 to 14.75	9.94 L/hr Interval 7.89 to 12.53	8.98 L/hr Interval 7.16 to 11.27

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

The AUC0-24hr of GZR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
AUC0-24hr of GZR at Steady State	1.45 µM*hr Interval 1.08 to 1.94	1.42 µM*hr Interval 1.0 to 2.02	0.77 µM*hr Interval 0.48 to 1.23	1.66 µM*hr Interval 1.16 to 2.39

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

The Cmax of GZR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Cmax of GZR	0.25 µM Interval 0.17 to 0.35	0.19 µM Interval 0.12 to 0.31	0.09 µM Interval 0.05 to 0.18	0.29 µM Interval 0.18 to 0.47

PRIMARY outcome

Timeframe: Week 4: Predose

The Ctrough of GZR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=16 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Ctrough of GZR	16.20 nM Interval 12.27 to 21.38	16.27 nM Interval 11.97 to 22.1	13.79 nM Interval 9.55 to 19.9	16.17 nM Interval 12.78 to 20.45

PRIMARY outcome

Timeframe: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Population: No participants are included in the analysis as the CL/F of GZR was not calculable due to nonlinear PK.

The CL/F of GZR at steady state (Week 4) was determined in each cohort.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 36 weeks

Population: All randomized participants who received ≥1 dose of study drug are included.

The percentage of participants with ≥1 AE is reported in each cohort. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Percentage of Participants With ≥1 Adverse Event (AE)	81.8 Percentage of Participants	76.5 Percentage of Participants	85.7 Percentage of Participants	81.8 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: All randomized participants who received ≥1 dose of study drug are included.

The percentage of participants discontinuing study therapy due to an AE is reported in each cohort. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Percentage of Participants Discontinuing Study Treatment Due to an AE	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 24

Population: All randomized participants who received ≥1 dose of study treatment are included.

The percentage of participants achieving SVR12, defined as hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantification (LLOQ) 12 weeks after completing study therapy, was determined in each cohort.

Outcome measures

Outcome measures
Measure	Age Cohort 1: 12 to <18 Years: Mini and Expanded n=22 Participants Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to <12 Years: Mini and Expanded n=17 Participants Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3: 3 to <7 Years: Mini n=7 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3: 3 to <7 Years: Expanded n=11 Participants Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)	100.0 Percentage of Participants Interval 84.6 to 100.0	100.0 Percentage of Participants Interval 80.5 to 100.0	100.0 Percentage of Participants Interval 59.0 to 100.0	100.0 Percentage of Participants Interval 71.5 to 100.0

Adverse Events

Age Cohort 1: 12 to < 18 Years

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Age Cohort 2: 7 to < 12 Years

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Age Cohort 3 Mini: 3 to < 7 Years

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Age Cohort 3 Expanded: 3 to < 7 Years

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Age Cohort 1: 12 to < 18 Years n=22 participants at risk Pediatric participants 12 to \<18 years of age received EBR/GZR 50 mg/100 mg FDC tablets once daily for 12 weeks.	Age Cohort 2: 7 to < 12 Years n=17 participants at risk Participants who are 7 to \<12 years of age received EBR/GZR 30 mg/60 mg pediatric granules once daily for 12 weeks.	Age Cohort 3 Mini: 3 to < 7 Years n=7 participants at risk Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR (weight-based dosing) once daily for 12 weeks. The Mini cohort consists of the first 7 participants enrolled into Age Cohort 3. Participants \<20 kg received EBR/GZR 15 mg/30 mg, and participants ≥20 kg received EBR/GZR 15 mg/50 mg.	Age Cohort 3 Expanded: 3 to < 7 Years n=11 participants at risk Participants who are 3 to \<7 years of age received a pediatric formulation of EBR/GZR 25 mg/50 mg once daily for 12 weeks. The Expanded cohort consists of 11 participants enrolled after the Mini Cohort of 7 participants.
Gastrointestinal disorders Dyspepsia	0.00% 0/22 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	0.00% 0/17 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	0.00% 0/7 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	9.1% 1/11 • Number of events 1 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.
Injury, poisoning and procedural complications Hand fracture	4.5% 1/22 • Number of events 1 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	0.00% 0/17 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	0.00% 0/7 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.	0.00% 0/11 • Up to 36 weeks for nonserious AEs (NSAEs) and serious AEs (SAEs), and up to approximately 49 weeks for all-cause mortality. All participants who received ≥1 dose of study drug are included. All-cause mortality is based on all randomized participants.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of this study may be published or presented at scientific meetings. The sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER