Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C, Chronic, Simeprevir, Daclatasvir, Sofosbuvir, Decompensated Liver Disease
Brief summary
The purpose of this study is to assess the efficacy of a 12-week regimen containing simeprevir, daclatasvir and sofosbuvir in participants with decompensated liver disease (the liver function is insufficient) due to genotype 1 or 4 Hepatitis (inflammation of the liver) C virus (HCV) infection by assessing sustained virologic response 12-weeks after the end of study drug treatment (SVR12).
Detailed description
This is an open-label (all people know which treatment the participants receive) Phase 2 study to investigate the efficacy, safety and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir in treatment-naive (participants have never received HCV treatment with any approved or investigational agent) and treatment - experienced (participants have failed at least one previous course of \[Pegylated\] interferon \[(Peg)IFN\], with or without Ribavirin) participants. Participants will be assigned to 1 of 2 panels: Panel 1 (n=20): Child-Pugh score less than (\<) 7 with evidence of portal hypertension (confirmed by presence of esophageal varices or HVPG greater than or equal to \[\>=\] 10 mm Hg); Panel 2 (n=20): Child-Pugh score 7 to 9 (extremes included). The total study duration for each participant will be approximately 276 weeks. The study will consist of 3 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (from Week 4 to 16) and follow-up Phase (until 5 years after the actual end of study drug treatment). Participants will receive simeprevir (150 milligram \[mg\] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.
Interventions
DRUGSimeprevir
Simeprevir 150 milligram (mg) capsule orally once daily for 12 weeks
DRUGDaclatasvir
Daclatasvir 60 mg tablet orally once daily for 12 weeks
DRUGSofosbuvir
Sofosbuvir 400 mg tablet orally once daily for 12 weeks
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (\>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis * HCV genotype 1 or 4 infection and HCV RNA plasma level \>10,000 international unit per milliliter (IU/mL) (both determined at screening) * Presence of cirrhosis, which is defined as a FibroScan with a result of \>14.5 kilopascals (kPa) at Screening * HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin \[RBV\]). Last dose in this previous course should have occurred at least 2 months prior to Screening * Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension \[confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (\>=) 10 millimeter of mercury (mm Hg)\], Panel 2: Child-Pugh B (moderate hepatic impairment) 7 to 9 (extremes included)
Exclusion criteria
* Co-infection with any HCV genotype * Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening) * Co-infection with hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive) * Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, 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-HCV liver disease considered clinically significant by the Investigator * Use of any disallowed therapies before the planned first dose of study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) | Week 24 | Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) | Week 16 and Week 36 | Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was \<LLOQ detectable or undetectable at 4 weeks and 24 weeks respectively after the end of study drug treatment. The LLOQ value was 15 IU/mL. |
| Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment in Participants Not Achieving SVR | Baseline, Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3 after end of treatment | Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. All participants in this study achieved SVR12. Therefore, reasons for not achieving SVR12 are not applicable. |
| Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Follow-up Week 24 (Week 36) | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8 | Tmax is the time to reach maximum observed plasma concentration. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8 | The AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after dosing. |
| Percentage of Participants With On-Treatment Virologic Response | Week 1, 2, 4, 6, 8, 10, 12 | On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. The following thresholds were considered at any time point: \<LLOQ undetectable, \<LLOQ detectable, and \<LLOQ undetectable or detectable. The LLOQ value was 15 IU/mL. Very rapid virologic response (vRVR) is undetectable HCV RNA at Week 2 while on treatment and Rapid virologic response (RVR) is undetectable HCV RNA at Week 4 while on treatment. |
| Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8 | The Cmin is the minimum observed plasma concentration. |
| Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8 | The C0h is the pre-dose plasma concentration. |
| Percentage of Participants With On-treatment Failure | Week 12 | On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment. |
| Percentage of Participants With Viral Relapse | Week 16, 24 and 36 | Viral relapse is defined as participants who do 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 (15 IU/mL) at Week 16, 24 or 36. |
| Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up | Week 24 post treatment until the end of 3-year follow-up | Percentage of participants with SVR12 who maintained to have HCV RNA \<LLOQ (15 IU/mL) until the end of 3 years follow up were reported. |
| Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8 | The Cmax is the maximum observed plasma concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Panel 1 SMV 150mg/DCV 60mg/SOF 400mg Participants with Child-Pugh score \<7 with evidence of portal hypertension (confirmed by presence of esophageal varices or hepatic venous pressure gradient \[HVPG\] greater than or equal to 10 millimeters of mercury \[mm Hg\]) received simeprevir (150 milligram \[mg\] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks. | 19 |
| Panel 2 SMV 150mg/DCV 60mg/SOF 400mg Participants with Child-Pugh score 7 to 9 (extremes included) received simeprevir (150 mg capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks. | 21 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Phase (3 Years) | Death | 0 | 1 |
| Follow-up Phase (3 Years) | Lost to Follow-up | 4 | 1 |
| Follow-up Phase (3 Years) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Panel 1 SMV 150mg/DCV 60mg/SOF 400mg | Panel 2 SMV 150mg/DCV 60mg/SOF 400mg | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 61 years | 58.5 years |
| Region of Enrollment United States | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 15 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 19 | 15 / 21 |
| serious Total, serious adverse events | 4 / 19 | 10 / 21 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment.
Time frame: Week 24
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) | 100 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) | 100 Percentage of Participants |
Secondary
Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36)
Time frame: Follow-up Week 24 (Week 36)
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug. Here, 'n' signifies number of participants evaluable for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Baseline : ALT | 137.8 Units per Liter (U/L) | Standard Deviation 101.9 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Baseline : AST | 119.1 Units per Liter (U/L) | Standard Deviation 80.57 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Follow-Up Week 24 : ALT | 34.8 Units per Liter (U/L) | Standard Deviation 11.3 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Follow-Up Week 24 : AST | 39.2 Units per Liter (U/L) | Standard Deviation 21.86 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Follow-Up Week 24 : AST | 35.0 Units per Liter (U/L) | Standard Deviation 10.31 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Baseline : ALT | 60.9 Units per Liter (U/L) | Standard Deviation 29.52 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Follow-Up Week 24 : ALT | 32.3 Units per Liter (U/L) | Standard Deviation 9.75 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) | Baseline : AST | 83.5 Units per Liter (U/L) | Standard Deviation 35.68 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after dosing.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Population: Pharmacokinetic (PK) analysis set included all participants who received atleast 1 dose of study drug and had valid pharmacokinetic profile. Here 'n' signifies number of participants analyzed for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 113835 ng.h/mL | Standard Deviation 91598 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 98568 ng.h/mL | Standard Deviation 80037 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 16487 ng.h/mL | Standard Deviation 6323 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 15574 ng.h/mL | Standard Deviation 5347 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | 2870 ng.h/mL | Standard Deviation 978 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | 2746 ng.h/mL | Standard Deviation 963 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 17900 ng.h/mL | Standard Deviation 6320 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 18132 ng.h/mL | Standard Deviation 7469 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 22829 ng.h/mL | Standard Deviation 15394 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 142162 ng.h/mL | Standard Deviation 80217 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | 3915 ng.h/mL | Standard Deviation 1258 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 207221 ng.h/mL | Standard Deviation 162168 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 21118 ng.h/mL | Standard Deviation 11301 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 17858 ng.h/mL | Standard Deviation 7726 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | 3933 ng.h/mL | Standard Deviation 1315 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 20787 ng.h/mL | Standard Deviation 10741 |
Secondary
Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The Cmax is the maximum observed plasma concentration.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Population: Pharmacokinetic (PK) analysis set included all participants who received atleast 1 dose of study drug and had valid pharmacokinetic profile. Here 'n' signifies number of participants analyzed for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 1403 nanogram per milliliter (ng/mL) | Standard Deviation 369 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 1072 nanogram per milliliter (ng/mL) | Standard Deviation 313 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 (test) | 6029 nanogram per milliliter (ng/mL) | Standard Deviation 3936 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | 1571 nanogram per milliliter (ng/mL) | Standard Deviation 738 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 (reference) | 6976 nanogram per milliliter (ng/mL) | Standard Deviation 4439 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | 1276 nanogram per milliliter (ng/mL) | Standard Deviation 856 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 1404 nanogram per milliliter (ng/mL) | Standard Deviation 361 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 1187 nanogram per milliliter (ng/mL) | Standard Deviation 397 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 1594 nanogram per milliliter (ng/mL) | Standard Deviation 952 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 1561 nanogram per milliliter (ng/mL) | Standard Deviation 720 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 (reference) | 7726 nanogram per milliliter (ng/mL) | Standard Deviation 3946 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 (test) | 10498 nanogram per milliliter (ng/mL) | Standard Deviation 7492 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 1145 nanogram per milliliter (ng/mL) | Standard Deviation 440 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 1210 nanogram per milliliter (ng/mL) | Standard Deviation 543 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | 1615 nanogram per milliliter (ng/mL) | Standard Deviation 986 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | 1527 nanogram per milliliter (ng/mL) | Standard Deviation 993 |
Secondary
Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The Cmin is the minimum observed plasma concentration.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Population: PK analysis set included all participants who received atleast 1 dose of study drug and had valid pharmacokinetic profile. Here 'n' signifies number of participants analyzed for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 442 ng/mL | Standard Deviation 192 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 3133 ng/mL | Standard Deviation 3410 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 2639 ng/mL | Standard Deviation 2725 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 414 ng/mL | Standard Deviation 230 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | NA ng/mL | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | NA ng/mL | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 419 ng/mL | Standard Deviation 198 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 443 ng/mL | Standard Deviation 213 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 523 ng/mL | Standard Deviation 392 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | NA ng/mL | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 4363 ng/mL | Standard Deviation 3081 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 441 ng/mL | Standard Deviation 254 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 6955 ng/mL | Standard Deviation 6035 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | NA ng/mL | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 519 ng/mL | Standard Deviation 275 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 660 ng/mL | Standard Deviation 416 |
Secondary
Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment in Participants Not Achieving SVR
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. All participants in this study achieved SVR12. Therefore, reasons for not achieving SVR12 are not applicable.
Time frame: Baseline, Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3 after end of treatment
Population: The ITT analysis set who failed achieving SVR. Since all participants achieved SVR, the number of participants for this endpoint analysis was zero.
Secondary
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.
Time frame: Week 12
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug. Here N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-treatment Failure | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 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 HCV RNA results satisfying a specified threshold. The following thresholds were considered at any time point: \<LLOQ undetectable, \<LLOQ detectable, and \<LLOQ undetectable or detectable. The LLOQ value was 15 IU/mL. Very rapid virologic response (vRVR) is undetectable HCV RNA at Week 2 while on treatment and Rapid virologic response (RVR) is undetectable HCV RNA at Week 4 while on treatment.
Time frame: Week 1, 2, 4, 6, 8, 10, 12
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug. Here, 'n' signifies number of participants evaluable for this outcome measure at specific time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 2: < 15 IU/mL undetectable (vRVR) | 52.6 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 15 IU/mL detectable | 5.3 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 2 : >= 15 IU/mL | 10.5 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 15 IU/mL undetectable | 94.7 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 4 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 8 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 15 IU/mL detectable | 11.1 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 8: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 2 : < 100 IU/mL | 94.7 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 15 IU/mL detectable | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 4: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 15 IU/mL undetectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 1: < 15 IU/mL undetect/detectable | 27.8 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 10 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 15 IU/mL detectable | 5.6 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 2: < 15 IU/mL undetect/detectable | 89.5 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 10: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 15 IU/mL undetectable (RVR) | 94.4 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 15 IU/mL detectable | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 15 IU/mL Undetectable | 16.7 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 15 IU/mL undetectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 6 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 12 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 2 : < 15 IU/mL detectable | 36.8 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 12 :< 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 12: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 1 : >= 15 IU/mL | 72.2 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 12 : < 15 IU/mL detectable | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 6: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 12 : < 15 IU/mL undetectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 100 IU/mL | 61.1 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 12 : < 15 IU/mL undetectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 1 : >= 15 IU/mL | 76.2 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 100 IU/mL | 38.1 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 1: < 15 IU/mL undetect/detectable | 23.8 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 15 IU/mL detectable | 19.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 1 : < 15 IU/mL Undetectable | 4.8 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 2 : >= 15 IU/mL | 47.6 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 2 : < 100 IU/mL | 71.4 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 2: < 15 IU/mL undetect/detectable | 52.4 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 2 : < 15 IU/mL detectable | 19.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 2: < 15 IU/mL undetectable (vRVR) | 33.3 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 4 : >= 15 IU/mL | 9.5 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 4: < 15 IU/mL undetect/detectable | 90.5 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 15 IU/mL detectable | 28.6 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 4 : < 15 IU/mL undetectable (RVR) | 61.9 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 6 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 6: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 15 IU/mL detectable | 20.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 6 : < 15 IU/mL undetectable | 80.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 8 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 8: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 15 IU/mL detectable | 4.8 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 8 : < 15 IU/mL undetectable | 95.2 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 10 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 10: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 15 IU/mL detectable | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 10 : < 15 IU/mL undetectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 12 : >= 15 IU/mL | 0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 12 :< 100 IU/mL | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 12: < 15 IU/mL undetect/detectable | 100.0 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With On-Treatment Virologic Response | Week 12 : < 15 IU/mL detectable | 0 Percentage of Participants |
Secondary
Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up
Percentage of participants with SVR12 who maintained to have HCV RNA \<LLOQ (15 IU/mL) until the end of 3 years follow up were reported.
Time frame: Week 24 post treatment until the end of 3-year follow-up
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up | 78.9 Percentage of participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up | 85.7 Percentage of participants |
Secondary
Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24)
Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was \<LLOQ detectable or undetectable at 4 weeks and 24 weeks respectively after the end of study drug treatment. The LLOQ value was 15 IU/mL.
Time frame: Week 16 and Week 36
Population: The intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug. Here , 'n' signifies number of participants evaluable for this outcome measure at specific time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) | SVR 4 | 100 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) | SVR 24 | 100 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) | SVR 4 | 100 Percentage of Participants |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) | SVR 24 | 100 Percentage of Participants |
Secondary
Percentage of Participants With Viral Relapse
Viral relapse is defined as participants who do 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 (15 IU/mL) at Week 16, 24 or 36.
Time frame: Week 16, 24 and 36
Population: The ITT analysis set who failed achieving SVR. Since all participants achieved SVR, the number of participants for this endpoint (viral relapse) analysis was zero.
Secondary
Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The C0h is the pre-dose plasma concentration.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Population: PK analysis set included all participants who received atleast 1 dose of study drug and had valid pharmacokinetic profile. Here 'n' signifies number of participants analyzed for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 3577 nanogram/milliliter (ng/mL) | Standard Deviation 3685 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 3160 nanogram/milliliter (ng/mL) | Standard Deviation 3725 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 494 nanogram/milliliter (ng/mL) | Standard Deviation 279 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 492 nanogram/milliliter (ng/mL) | Standard Deviation 232 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | NA nanogram/milliliter (ng/mL) | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | NA nanogram/milliliter (ng/mL) | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 484 nanogram/milliliter (ng/mL) | Standard Deviation 236 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 478 nanogram/milliliter (ng/mL) | Standard Deviation 262 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 8 | 572 nanogram/milliliter (ng/mL) | Standard Deviation 450 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 2 | 5218 nanogram/milliliter (ng/mL) | Standard Deviation 3461 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 2 | NA nanogram/milliliter (ng/mL) | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir : Week 8 | 8577 nanogram/milliliter (ng/mL) | Standard Deviation 7398 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007 : Week 2 | 490 nanogram/milliliter (ng/mL) | Standard Deviation 282 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 2 | 646 nanogram/milliliter (ng/mL) | Standard Deviation 384 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir : Week 8 | NA nanogram/milliliter (ng/mL) | — |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir : Week 8 | 824 nanogram/milliliter (ng/mL) | Standard Deviation 476 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Tmax is the time to reach maximum observed plasma concentration.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Population: Pharmacokinetic (PK) analysis set included all participants who received atleast 1 dose of study drug and had valid pharmacokinetic profile. Here 'n' signifies number of participants analyzed for this outcome measure at specific time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir: Week 2 | 6.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir: Week 8 | 6.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir: Week 2 | 3.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir: Week 8 | 2.50 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir: Week 2 | 1.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir: Week 8 | 1.75 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007: Week 2 | 4.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007: Week 8 | 4.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007: Week 8 | 4.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir: Week 2 | 8.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir: Week 2 | 2.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Simeprevir: Week 8 | 8.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | GS-331007: Week 2 | 4.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir: Week 2 | 4.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Sofosbuvir: Week 8 | 2.00 Hours |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) | Daclatasvir: Week 8 | 4.00 Hours |