Hepatitis C Virus (HCV)
Conditions
Keywords
Chronic Hepatitis C Virus, Glecaprevir, Pibrentasvir, Pharmacokinetic, Treatment naïve, Treatment experienced, Interferon (IFN), Pegylated interferon (pegIFN), Ribavirin (RBV), Sofosbuvir, Non-cirrhotic cirrhosis, Compensated (Child-Pugh A) cirrhosis
Brief summary
The objectives of this study are to assess the pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir adult formulation in adolescents ages 12 to 17 years and a pediatric formulation of glecaprevir and pibrentasvir in children ages 3 to \< 12 years.
Detailed description
This was a multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of glecaprevir (GLE) and pibrentasvir (PIB) treatment for 8, 12, or 16 weeks in hepatitis C virus (HCV) genotype 1 - 6 (GT1 - GT6)-infected pediatric participants 3 to \< 18 years of age, with or without compensated cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, who are either treatment-naïve (TN), treatment-experienced (TE) with pegylated interferon (pegIFN) with or without ribavirin (RBV), or TE with sofosbuvir (SOF) + RBV with or without pegIFN. The study was divided into 2 parts, according to the formulation of GLE/PIB administered. Part 1 of the study enrolled HCV GT1 - GT6 infected adolescent participants into the 12 to \< 18 years old age group who were willing to swallow the adult formulation of GLE/PIB (Cohort 1). Part 2 of the study enrolled HCV GT1 - GT6 infected pediatric participants divided into the 9 to \< 12 (Cohort 2), 6 to \< 9 (Cohort 3), and 3 to \< 6 (Cohort 4) years old age groups, to receive the pediatric formulation of GLE + PIB. Part 1 enrolled first and once the pediatric formulation was available enrollment into Part 2 commenced, with each cohort enrolled in parallel. In each cohort, the first group of participants were enrolled into an intense pharmacokinetics (IPK) portion to characterize the PK and safety in each age group, followed by enrollment into a non-IPK safety/efficacy portion. Study participants enrolled in the IPK portion must have been HIV-negative, treatment-naive, and have an identified HCV genotype. In the IPK portion the first approximately six participants received an initial proposed dose of GLE and PIB based on the child's weight and age at screening. PK samples from these participants were evaluated to determine if therapeutic efficacious exposures were attained, comparable to those of adults, and if any dose adjustments were needed. After the intensive PK analysis results for the first six participants were available, enrollment of the remaining IPK portion resumed with subsequent participants receiving an adjusted final dose as applicable. Additional participants may have been required for further intensive PK analysis per age cohort if therapeutic exposure targets were not achieved. Enrollment into the non-IPK safety and efficacy portions began when the dosing recommendations per age group based on the PK and clinical data from the IPK analysis were ascertained.
Interventions
DRUGGlecaprevir/Pibrentasvir Adult Formulation
Co-formulated film-coated tablet (100 mg/40 mg)
DRUGGlecaprevir + Pibrentasvir Pediatric Formulation
Film-coated pellets/granules (15.67%/8.25%) administered by mixing with a small amount (1-2 teaspoons) of a soft food vehicle, such as hazelnut spread, Greek yogurt, or peanut butter.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Hepatitis C virus (HCV) infection demonstrated by positive anti-HCV antibody (Ab) and HCV ribonucleic acid (RNA) greater than or equal to 1000 International Unit (IU)/mL * Subjects participating in the intense pharmacokinetic (IPK) part must have been HCV treatment-naive, with or without compensated cirrhosis (Child-Pugh A), human immunodeficiency virus type 1 (HIV-1) negative and must have had a Screening laboratory result indicating HCV genotype (GT) 1, 2, 3, 4, 5, or 6-infection.
Exclusion criteria
* Females who were pregnant or breastfeeding * Positive test result for hepatitis B surface antigen (HbsAg) or positive test result for hepatitis B virus deoxyribonucleic acid (DNA) * Participants with other known liver diseases * Decompensated cirrhosis defined as: presence of ascites, history of variceal bleeding, lab values consistent with Child-Pugh class B or C cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir | Week 2 from predose to 24 hours post-dose | The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of GLE was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis. |
| Steady-state AUC0-24 of Pibrentasvir | Week 2 from predose to 24 hours post-dose | The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of PIB was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis. |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration) | SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last actual dose of study drug. Plasma HCV RNA levels were collected using the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0. SVR12 was considered a primary efficacy endpoint by the United States (US) regulatory agency and was considered secondary outside of the US. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Clearance of Pibrentasvir From Plasma | Week 2 from predose to 24 hours post-dose | CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis. |
| Percentage of Participants Who Experienced On-treatment Virologic Failure | Up to Week 8, 12, or 16 (depending on treatment duration) | On-treatment virologic failure is defined as meeting one of the following: * A confirmed (defined as two consecutive HCV RNA measurements) increase of \> 1 log₁₀ IU/mL above nadir during treatment; * Confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during treatment; * HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | Up to 12 weeks after the last dose of study drug (Week 20, 24, or 28 depending on treatment duration) | Post-treatment relapse is defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA \< 15 IU/mL at the end of treatment; excluding participants who had been shown to be re-infected. |
| Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | From the end of treatment up to post-treatment Week 144 | Reinfection is defined as confirmed HCV RNA ≥ 15 IU/mL in the post-treatment period in a participant who had HCV RNA \< 15 IU/mL at the Final Treatment Visit, along with post-treatment detection of a different HCV genotype, subtype, or clade compared with Baseline, as determined by phylogenetic analysis of the nonstructural viral protein 3 (NS3) or NS5A, and/or NS5B gene sequences. |
| Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 1 How Convenient or Inconvenient Was it to Prepare the Dose? was answered as very convenient, convenient, borderline, inconvenient, or very inconvenient. |
| Maximum Plasma Concentration (Cmax) of Glecaprevir | Week 2 from predose to 24 hours post-dose | Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose. |
| Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation. Question 5 How Easy or Difficult Was it for the Child to Swallow the Medicine? was answered as very easy, easy, borderline, difficult, or very difficult. |
| Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 3 Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? was answered as Yes or No. |
| Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Final treatment visit (up to Week 8, 12, or 16 depending on treatment duration) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4 Did You Experience Any Resistance When Feeding the Child the Medicine? was answered as Yes or No. |
| Palatability Questionnaire Question 4a: Type of Feeding Resistance | Up to final treatment visit (up to Week 8, 12, or 16 depending on treatment duration) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4a Type of feeding resistance? tracks feeding resistance experienced at any time during treatment, and was answered as Did not like taste of medicine, Did not like texture of medicine, Did not like the soft food used, Did not like to swallow the amount of medicine, or Unrelated to the medicine. |
| Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | Final treatment visit (up to Week 8, 12, or 16, depending on duration of treatment) | For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 2 How Long Did it Typically Take for the Child to Take the Dose? was answered as 5 minutes or less, 5 to 15 minutes, 15 to 30 minutes, or more than 30 minutes. |
| Apparent Clearance (CL/F) of Glecaprevir From Plasma | Week 2 from predose to 24 hours post-dose | CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis. |
| Maximum Plasma Concentration of Pibrentasvir | Week 2 from predose to 24 hours post-dose | Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose. |
Countries
Belgium, Canada, Germany, Japan, Puerto Rico, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 38 sites in North America, Europe, and Japan. Cohort 1 enrolled adolescent participants aged 12 to \< 18 years old. Subsequently, children aged 9 to \< 12 (Cohort 2), 6 to \< 9 (Cohort 3), and 3 to \< 6 (Cohort 4) years old were enrolled in parallel.
Pre-assignment details
In each cohort participants were first enrolled into an intense pharmacokinetic (IPK) portion to characterize the PK and safety, followed by a non-IPK safety/efficacy part. PK samples from the first 6 participants in the IPK part were analyzed to determine the final dose used for the remaining IPK participants and in the non-IPK group. A total of 129 participants were enrolled and 127 participants received at least 1 dose of study drug and were included in the intention-to-treat population.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years Adolescents aged 12 to \< 18 years old received the adult formulation of glecaprevir (GLE)/pibrentasvir (PIB) 100 mg/40 mg co-formulated film-coated tablets for a once daily (QD) total dose of 300 mg/120 mg by mouth for 8, 12, or 16 weeks depending on hepatitis C virus (HCV) genotype, cirrhosis status, and prior treatment experience. | 47 |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years Children aged 9 to \< 12 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The final dose for children weighing 30 to \< 45 kg was GLE 250 mg + PIB 100 mg. | 29 |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years Children aged 6 to \< 9 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The final dose for children weighing 20 to \< 30 kg was GLE 200 mg + PIB 80 mg; one participant received GLE 250 mg + PIB 100 mg based on weight at screening. | 27 |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years Children aged 3 to \< 6 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The final dose for children weighing 12 to \< 20 kg was GLE 150 mg + PIB 60 mg; one participant received GLE 200 mg + PIB 80 mg based on weight at screening. | 24 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 5 | 4 | 3 |
| Overall Study | Partially Dosed; Refused to Swallow Entire Dose | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years |
|---|---|---|---|---|---|
| Age, Continuous | 9.79 years STANDARD_DEVIATION 4.14 | 3.79 years STANDARD_DEVIATION 0.78 | 10.00 years STANDARD_DEVIATION 0.85 | 7.11 years STANDARD_DEVIATION 0.89 | 14.26 years STANDARD_DEVIATION 1.51 |
| Baseline Fibrosis Stage F0-F1 | 123 Participants | 24 Participants | 28 Participants | 26 Participants | 45 Participants |
| Baseline Fibrosis Stage F2 | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Baseline Fibrosis Stage F3 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Baseline Fibrosis Stage F4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Co-infection with Human Immunodeficiency Virus (HIV) No | 124 Participants | 24 Participants | 29 Participants | 26 Participants | 45 Participants |
| Co-infection with Human Immunodeficiency Virus (HIV) Yes | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 4 Participants | 5 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 20 Participants | 24 Participants | 23 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV Ribonucleic Acid (RNA) Level | 6.07 Log₁₀ IU/mL | 5.83 Log₁₀ IU/mL | 6.20 Log₁₀ IU/mL | 5.89 Log₁₀ IU/mL | 6.20 Log₁₀ IU/mL |
| Hepatitis C Virus Genotype Genotype 1 | 95 Participants | 17 Participants | 19 Participants | 22 Participants | 37 Participants |
| Hepatitis C Virus Genotype Genotype 2 | 5 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Hepatitis C Virus Genotype Genotype 3 | 22 Participants | 7 Participants | 8 Participants | 3 Participants | 4 Participants |
| Hepatitis C Virus Genotype Genotype 4 | 5 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Hepatitis C Virus Genotype Genotype 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis C Virus Genotype Genotype 6 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior HCV Treatment History Experienced | 13 Participants | 0 Participants | 2 Participants | 0 Participants | 11 Participants |
| Prior HCV Treatment History Naive | 114 Participants | 24 Participants | 27 Participants | 27 Participants | 36 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 20 Participants | 4 Participants | 5 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Multiple | 7 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 90 Participants | 16 Participants | 21 Participants | 18 Participants | 35 Participants |
| Sex: Female, Male Female | 70 Participants | 12 Participants | 15 Participants | 17 Participants | 26 Participants |
| Sex: Female, Male Male | 57 Participants | 12 Participants | 14 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 29 | 0 / 27 | 0 / 24 | 0 / 80 | 0 / 127 |
| other Total, other adverse events | 31 / 47 | 15 / 29 | 16 / 27 | 17 / 24 | 48 / 80 | 79 / 127 |
| serious Total, serious adverse events | 0 / 47 | 0 / 29 | 0 / 27 | 0 / 24 | 0 / 80 | 0 / 127 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last actual dose of study drug. Plasma HCV RNA levels were collected using the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0. SVR12 was considered a primary efficacy endpoint by the United States (US) regulatory agency and was considered secondary outside of the US.
Time frame: 12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
Population: Intention-to-treat population: all participants who received at least 1 dose of study drug; Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backwards imputation were counted as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 100 percentage of participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 93.1 percentage of participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 100 percentage of participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 95.8 percentage of participants |
| Cohorts 2-4: Pediatric Formulation GLE + PIB; 3 to < 12 Years | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 96.3 percentage of participants |
| Total | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 97.6 percentage of participants |
Primary
Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir
The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of GLE was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) is summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir | 4790 ng*h/mL |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir | 7870 ng*h/mL |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir | 6860 ng*h/mL |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir | 7520 ng*h/mL |
Primary
Steady-state AUC0-24 of Pibrentasvir
The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of PIB was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) was summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Steady-state AUC0-24 of Pibrentasvir | 1380 ng*h/mL |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Steady-state AUC0-24 of Pibrentasvir | 2200 ng*h/mL |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Steady-state AUC0-24 of Pibrentasvir | 1640 ng*h/mL |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Steady-state AUC0-24 of Pibrentasvir | 1790 ng*h/mL |
Secondary
Apparent Clearance (CL/F) of Glecaprevir From Plasma
CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) was summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Apparent Clearance (CL/F) of Glecaprevir From Plasma | 62.6 L/h |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Apparent Clearance (CL/F) of Glecaprevir From Plasma | 31.8 L/h |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Apparent Clearance (CL/F) of Glecaprevir From Plasma | 29.1 L/h |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Apparent Clearance (CL/F) of Glecaprevir From Plasma | 19.9 L/h |
Secondary
Apparent Clearance of Pibrentasvir From Plasma
CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) was summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Apparent Clearance of Pibrentasvir From Plasma | 86.9 L/h |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Apparent Clearance of Pibrentasvir From Plasma | 45.4 L/h |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Apparent Clearance of Pibrentasvir From Plasma | 48.7 L/h |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Apparent Clearance of Pibrentasvir From Plasma | 33.6 L/h |
Secondary
Maximum Plasma Concentration (Cmax) of Glecaprevir
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) was summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Maximum Plasma Concentration (Cmax) of Glecaprevir | 1040 ng/mL |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Maximum Plasma Concentration (Cmax) of Glecaprevir | 1370 ng/mL |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Maximum Plasma Concentration (Cmax) of Glecaprevir | 1600 ng/mL |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Maximum Plasma Concentration (Cmax) of Glecaprevir | 1530 ng/mL |
Secondary
Maximum Plasma Concentration of Pibrentasvir
Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose.
Time frame: Week 2 from predose to 24 hours post-dose
Population: Participants with intense pharmacokinetic samples who received the final dose regimen of GLE + PIB. One participant in Cohort 4 who received GLE 200 mg + PIB 80 mg based on weight (\> 20 kg) was summarized in Cohort 3 for PK analyses based on the actual dose received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Maximum Plasma Concentration of Pibrentasvir | 174 ng/mL |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Maximum Plasma Concentration of Pibrentasvir | 225 ng/mL |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Maximum Plasma Concentration of Pibrentasvir | 197 ng/mL |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Maximum Plasma Concentration of Pibrentasvir | 233 ng/mL |
Secondary
Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose?
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 1 How Convenient or Inconvenient Was it to Prepare the Dose? was answered as very convenient, convenient, borderline, inconvenient, or very inconvenient.
Time frame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Inconvenient | 6 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Convenient | 13 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very inconvenient | 0 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Borderline | 2 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very convenient | 7 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Borderline | 7 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Inconvenient | 1 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very inconvenient | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Convenient | 10 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very convenient | 9 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Borderline | 4 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very convenient | 9 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Convenient | 8 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Inconvenient | 1 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very inconvenient | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Inconvenient | 8 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Convenient | 31 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very convenient | 25 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Borderline | 13 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? | Very inconvenient | 1 Participants |
Secondary
Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose?
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 2 How Long Did it Typically Take for the Child to Take the Dose? was answered as 5 minutes or less, 5 to 15 minutes, 15 to 30 minutes, or more than 30 minutes.
Time frame: Final treatment visit (up to Week 8, 12, or 16, depending on duration of treatment)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 minutes or less | 22 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 to 15 minutes | 5 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 15 to 30 minutes | 1 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | More than 30 minutes | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 to 15 minutes | 4 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 15 to 30 minutes | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | More than 30 minutes | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 minutes or less | 23 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 15 to 30 minutes | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 to 15 minutes | 2 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | More than 30 minutes | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 minutes or less | 21 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | More than 30 minutes | 0 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 to 15 minutes | 11 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 5 minutes or less | 66 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? | 15 to 30 minutes | 1 Participants |
Secondary
Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food?
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 3 Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? was answered as Yes or No.
Time frame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Yes | 20 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Missing | 0 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | No | 8 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Yes | 19 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | No | 8 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | No | 3 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Yes | 19 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Yes | 58 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food? | No | 19 Participants |
Secondary
Palatability Questionnaire Question 4a: Type of Feeding Resistance
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4a Type of feeding resistance? tracks feeding resistance experienced at any time during treatment, and was answered as Did not like taste of medicine, Did not like texture of medicine, Did not like the soft food used, Did not like to swallow the amount of medicine, or Unrelated to the medicine.
Time frame: Up to final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like taste of medicine | 3 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like texture of medicine | 2 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like the soft food used | 3 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like to swallow the amount of medicine | 3 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Unrelated to the medicine | 0 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like to swallow the amount of medicine | 2 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like taste of medicine | 5 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like the soft food used | 2 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like texture of medicine | 2 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Unrelated to the medicine | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like texture of medicine | 5 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like the soft food used | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like to swallow the amount of medicine | 3 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Missing | 1 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Unrelated to the medicine | 1 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like taste of medicine | 6 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Unrelated to the medicine | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like texture of medicine | 9 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like to swallow the amount of medicine | 8 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like taste of medicine | 14 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4a: Type of Feeding Resistance | Did not like the soft food used | 5 Participants |
Secondary
Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine?
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4 Did You Experience Any Resistance When Feeding the Child the Medicine? was answered as Yes or No.
Time frame: Final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Yes | 6 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Missing | 0 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | No | 22 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Yes | 4 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | No | 23 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | No | 15 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Yes | 7 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Yes | 17 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? | No | 60 Participants |
Secondary
Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine?
For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation. Question 5 How Easy or Difficult Was it for the Child to Swallow the Medicine? was answered as very easy, easy, borderline, difficult, or very difficult.
Time frame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Population: Participants in the intention-to-treat population who completed the Palatability Questionnaire at the final treatment visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very easy | 10 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Easy | 13 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Borderline | 4 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Difficult | 1 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very difficult | 0 Participants |
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Missing | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Difficult | 0 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very easy | 8 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Borderline | 3 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Easy | 16 Participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very difficult | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Easy | 10 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Borderline | 1 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Difficult | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Missing | 1 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very difficult | 0 Participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very easy | 11 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very difficult | 0 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Missing | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Easy | 39 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Difficult | 1 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Very easy | 29 Participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? | Borderline | 8 Participants |
Secondary
Percentage of Participants Who Experienced On-treatment Virologic Failure
On-treatment virologic failure is defined as meeting one of the following: * A confirmed (defined as two consecutive HCV RNA measurements) increase of \> 1 log₁₀ IU/mL above nadir during treatment; * Confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during treatment; * HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment.
Time frame: Up to Week 8, 12, or 16 (depending on treatment duration)
Population: Intention-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
| Cohorts 2-4: Pediatric Formulation GLE + PIB; 3 to < 12 Years | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
| Total | Percentage of Participants Who Experienced On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With New Hepatitis C Virus Infection (Reinfection)
Reinfection is defined as confirmed HCV RNA ≥ 15 IU/mL in the post-treatment period in a participant who had HCV RNA \< 15 IU/mL at the Final Treatment Visit, along with post-treatment detection of a different HCV genotype, subtype, or clade compared with Baseline, as determined by phylogenetic analysis of the nonstructural viral protein 3 (NS3) or NS5A, and/or NS5B gene sequences.
Time frame: From the end of treatment up to post-treatment Week 144
Population: Intention-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
| Cohorts 2-4: Pediatric Formulation GLE + PIB; 3 to < 12 Years | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
| Total | Percentage of Participants With New Hepatitis C Virus Infection (Reinfection) | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment
Post-treatment relapse is defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA \< 15 IU/mL at the end of treatment; excluding participants who had been shown to be re-infected.
Time frame: Up to 12 weeks after the last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
Population: Participants in the ITT population who completed treatment (based on study drug duration) with HCV RNA \< 15 IU/mL at the final treatment visit and with at least one post-treatment HCV RNA value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Adult Formulation GLE/PIB; 12 to < 18 Years | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 0 percentage of participants |
| Cohort 2: Pediatric Formulation GLE + PIB; 9 to < 12 Years | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 3.6 percentage of participants |
| Cohort 3: Pediatric Formulation GLE + PIB; 6 to < 9 Years | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 0 percentage of participants |
| Cohort 4: Pediatric Formulation GLE + PIB; 3 to < 6 Years | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 0 percentage of participants |
| Cohorts 2-4: Pediatric Formulation GLE + PIB; 3 to < 12 Years | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 1.3 percentage of participants |
| Total | Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment | 0.8 percentage of participants |