Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C, Chronic, Simeprevir, Ledipasvir, Sofosbuvir
Brief summary
The purpose of this study is to evaluate the pharmacokinetic interactions between simeprevir and ledipasvir in a treatment regimen consisting of simeprevir (SMV), sofosbuvir (SOF), and ledipasvir (LDV) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype 1 infection.
Detailed description
This is an open-label (all people know the identity of the intervention), 2-panel, Phase 2, randomized (study medication assigned to participants by chance) study. The study will consist of 3 study phases: Screening Phase (5 weeks), an Open-label Treatment Phase (70 days for Panel 1 and 56 days for Panel 2), a Post-treatment Follow-up Phase (12 weeks after the actual end of treatment). Participants will receive a combination of the following treatments: Treatment A: SMV 150 milligram (mg) once daily; Treatment B: LDV 90 mg along with SOF 400 mg once daily; Treatment C: SOF 400 mg once daily. Participants will be randomly assigned to Panel 1 (Treatment AC followed by Treatment AB) and Panel 2 (Treatment B followed by Treatment AB). The total study duration will be approximately 27 weeks for participants in Panel 1 and 25 weeks for participants in Panel 2. Participants will be primarily accessed for pharmacokinetic parameters. Participants' safety will be monitored throughout the study.
Interventions
DRUGSimeprevir (SMV)
Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.
DRUGLedipasvir (LDV)
Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.
DRUGSofosbuvir (SOF)
Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2.
Sponsors
Janssen Sciences Ireland UC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants with Body Mass Index (weight in kilogram \[kg\] divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter kg/m\^2, extremes included * Participants must be treatment-naive (that is, have not received prior treatment with any approved or investigational drug) * Participants with HCV ribonucleic acid (RNA) plasma levels greater than (\>) 10,000 international unit per milliliter (IU/ml) and lower than 6,000,000 international unit per milliliter (IU/ml) at screening * Participants with absence of cirrhosis confirmed by FibroTest/Fibrosure score less or equal to 0.75 and an aspartate aminotransferase to platelet ration index less or equal to 2 or a Fibroscan less or equal to 14.6 kilopascale (kPA), performed within 6 months prior or during the screening period * Participants with documented chronic HCV infection: diagnosis of HCV infection \>6 months prior to screening, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes consistent with chronic hepatitis in a liver biopsy
Exclusion criteria
* Participant has infection/co-infection with HCV of a genotype other than genotype 1, human immunodeficiency virus (HIV) type 1 or 2 * Participant has any evidence of liver disease of non-HCV etiology. This includes, but is not limited to acute hepatitis A, active hepatitis B, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HC liver disease considered clinically significant by the investigator * Participant with significant co-morbidities, conditions or clinical significant findings during screening assessments that in the opinion of the investigator could compromise the participants' safety or could interfere with the Participant participating in and completing the study * Participant received an organ transplant (other than cornea or hair transplant or skin graft) * Participants have key protocol defined laboratory abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cmin is the minimum observed plasma concentration. |
| Maximum Plasma Concentration (Cmax) of Simeprevir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cmax is the maximum observed plasma concentration. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. |
| Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cmin is the minimum observed plasma concentration. |
| Maximum Plasma Concentration (Cmax) of Ledipasvir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cmax is the maximum observed plasma concentration. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau). |
| Fluctuation Index (FI) of Ledipasvir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg). |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2 | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Percentage of Participants With On-treatment Virologic Response | Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2) | On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold. The following thresholds were considered at any time point: less than (\<) lower limit of quantification (LLOQ) undetectable, \<LLOQ detectable and \<LLOQ undetectable/detectable. |
| Trough Plasma Concentration (Ctrough) of Simeprevir | Pre-dose on Day 14 and Day 28 | The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen. |
| Percentage of Participants With On-treatment Failure | Day 70 in Panel 1 and Day 56 in Panel 2 | On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (\>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of \>100 IU/mL in participants whose HCV RNA had previously been \<LLOQ while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to AEs, withdrawal of consent). |
| Percentage of Participants With Viral Relapse | Up to Week 12 follow-up phase after EOT | Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up. |
| Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence | Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2 | — |
| Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) | 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2) | SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA \<LLOQ detectable or undetectable. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. |
| Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau). |
| Fluctuation Index (FI) of Simeprevir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg). |
| Trough Plasma Concentration (Ctrough) of Ledipasvir | Pre-dose on Day 14 and Day 28 | The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir | Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28 | The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 41 participants were enrolled in the study, among them 40 participants (20 per panel) were randomized and treated. One participant was early terminated from the study, due to withdrawal of consent before randomization to study drug. All randomized participants received study drug and were included in the intent to treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14. From Day 15 until Day 70, participants received SMV 150 mg capsule and a fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF, orally and once daily. | 20 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) Participants received fixed dose combination (FDC) tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14. From Day 15 until Day 56, participants received SMV 150 mg capsule and a FDC tablet of 90 mg LDV/400 mg SOF, orally and once daily. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | Total |
|---|---|---|---|
| Age, Continuous | 50.5 years | 51 years | 51 years |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 20 | 15 / 20 |
| serious Total, serious adverse events | 2 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir | 9868 ng*h/mL | Standard Deviation 4930 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir | 17435 ng*h/mL | Standard Deviation 8772 |
90% CI: [1.6, 2]
Primary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir | 100492 nanogram hour per Milliliters (ng*h/mL) | Standard Deviation 115868 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir | 243564 nanogram hour per Milliliters (ng*h/mL) | Standard Deviation 159124 |
90% CI: [2.4, 3.8]
Primary
Maximum Plasma Concentration (Cmax) of Ledipasvir
The Cmax is the maximum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Maximum Plasma Concentration (Cmax) of Ledipasvir | 556 ng/mL | Standard Deviation 270 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Maximum Plasma Concentration (Cmax) of Ledipasvir | 930 ng/mL | Standard Deviation 466 |
90% CI: [1.4, 1.9]
Primary
Maximum Plasma Concentration (Cmax) of Simeprevir
The Cmax is the maximum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Maximum Plasma Concentration (Cmax) of Simeprevir | 6767 ng/mL | Standard Deviation 6362 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Maximum Plasma Concentration (Cmax) of Simeprevir | 13691 ng/mL | Standard Deviation 7775 |
90% CI: [2, 2.8]
Primary
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
The Cmin is the minimum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) | 319 ng/mL | Standard Deviation 178 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) | 557 ng/mL | Standard Deviation 307 |
90% CI: [1.5, 2]
Primary
Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
The Cmin is the minimum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) | 2411 nanogram per Milliliters (ng/mL) | Standard Deviation 3778 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) | 6701 nanogram per Milliliters (ng/mL) | Standard Deviation 4179 |
90% CI: [3.4, 6.5]
Secondary
Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau).
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir | 411 ng/mL | Standard Deviation 207 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir | 725 ng/mL | Standard Deviation 364 |
Secondary
Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau).
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir | 4196 ng/mL | Standard Deviation 4833 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir | 10139 ng/mL | Standard Deviation 6628 |
Secondary
Fluctuation Index (FI) of Ledipasvir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg).
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Fluctuation Index (FI) of Ledipasvir | 60.6 percentage fluctuation | Standard Deviation 19.7 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Fluctuation Index (FI) of Ledipasvir | 51.2 percentage fluctuation | Standard Deviation 0.17 |
Secondary
Fluctuation Index (FI) of Simeprevir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg).
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Fluctuation Index (FI) of Simeprevir | 144 percentage fluctuation | Standard Deviation 55.5 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Fluctuation Index (FI) of Simeprevir | 84.4 percentage fluctuation | Standard Deviation 36.5 |
Secondary
Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence
Time frame: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Since the data was to be analysed in the participants who did not achieve SVR, but all the participants achieved SVR in the study. Therefore the data was not collected for this outcome measure.
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events | 17 number of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events | 2 number of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events | 15 number of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events | 0 number of participants |
Secondary
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (\>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of \>100 IU/mL in participants whose HCV RNA had previously been \<LLOQ while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to AEs, withdrawal of consent).
Time frame: Day 70 in Panel 1 and Day 56 in Panel 2
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Failure | 0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Failure | 0 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Response
On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold. The following thresholds were considered at any time point: less than (\<) lower limit of quantification (LLOQ) undetectable, \<LLOQ detectable and \<LLOQ undetectable/detectable.
Time frame: Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL detectable | 15.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL detectable | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL undetectable (RVR) | 85.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 2: >= 15 IU/mL | 25.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 6: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL undetectable/detectable | 35.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL undetectable/detectable | 75.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 10: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL undetectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL detectable | 30.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 8: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL detectable | 15.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL undetectable (vRVR) | 45.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL detectable | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 1: >= 15 IU/mL | 65.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL undetectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 4: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL undetectable | 20.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL detectable | 0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL undetectable | 100.0 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL undetectable/detectable | 95.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL undetectable/detectable | NA percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL detectable | NA percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 1: >= 15 IU/mL | 60.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL undetectable/detectable | 40.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL detectable | 35.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 1: < 15 IU/mL undetectable | 5.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 2: >= 15 IU/mL | 35.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL undetectable/detectable | 65.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL detectable | 30.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 2: < 15 IU/mL undetectable (vRVR) | 35.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 4: >= 15 IU/mL | 5.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL detectable | 5.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 4: < 15 IU/mL undetectable (RVR) | 90.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 6: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL detectable | 5.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 6: < 15 IU/mL undetectable | 95.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 8: >= 15 IU/mL | 0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL undetectable/detectable | 100.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL detectable | 0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 8: < 15 IU/mL undetectable | 100.0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 10: >= 15 IU/mL | NA percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With On-treatment Virologic Response | Week 10: < 15 IU/mL undetectable | NA percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)
SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA \<LLOQ detectable or undetectable.
Time frame: 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) | SVR4 | 100 percentage of participants |
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) | SVR12 | 100 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) | SVR12 | 100 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) | SVR4 | 100 percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up.
Time frame: Up to Week 12 follow-up phase after EOT
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Percentage of Participants With Viral Relapse | 0 percentage of participants |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Percentage of Participants With Viral Relapse | 0 percentage of participants |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir | 4.07 Hour |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir | 6.00 Hour |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir | 6.00 hour (H) |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir | 6.00 hour (H) |
Secondary
Trough Plasma Concentration (Ctrough) of Ledipasvir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Time frame: Pre-dose on Day 14 and Day 28
Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Trough Plasma Concentration (Ctrough) of Ledipasvir | 376 ng/mL | Standard Deviation 211 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Trough Plasma Concentration (Ctrough) of Ledipasvir | 659 ng/mL | Standard Deviation 406 |
Secondary
Trough Plasma Concentration (Ctrough) of Simeprevir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Time frame: Pre-dose on Day 14 and Day 28
Population: The Intent-to-treat (ITT) analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | Trough Plasma Concentration (Ctrough) of Simeprevir | 3059 nanogram per Milliliters (ng/mL) | Standard Deviation 4236 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | Trough Plasma Concentration (Ctrough) of Simeprevir | 8453 nanogram per Milliliters (ng/mL) | Standard Deviation 6455 |