Trial Outcomes & Findings for A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection (NCT NCT02421211)
NCT ID: NCT02421211
Last Updated: 2019-03-28
Results Overview
The Cmin is the minimum observed plasma concentration.
COMPLETED
PHASE2
41 participants
Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
2019-03-28
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
Baseline characteristics by cohort
| Measure |
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])
n=20 Participants
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.
|
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
n=20 Participants
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.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.5 years
n=5 Participants
|
51 years
n=7 Participants
|
51 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
The Cmin is the minimum observed plasma concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
|
2411 nanogram per Milliliters (ng/mL)
Standard Deviation 3778
|
6701 nanogram per Milliliters (ng/mL)
Standard Deviation 4179
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
The Cmax is the maximum observed plasma concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=19 Participants
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.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Simeprevir
|
6767 ng/mL
Standard Deviation 6362
|
13691 ng/mL
Standard Deviation 7775
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=19 Participants
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.
|
|---|---|---|
|
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
|
243564 nanogram hour per Milliliters (ng*h/mL)
Standard Deviation 159124
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
The Cmin is the minimum observed plasma concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=18 Participants
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.
|
|---|---|---|
|
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
|
319 ng/mL
Standard Deviation 178
|
557 ng/mL
Standard Deviation 307
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
The Cmax is the maximum observed plasma concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=17 Participants
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.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Ledipasvir
|
556 ng/mL
Standard Deviation 270
|
930 ng/mL
Standard Deviation 466
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=17 Participants
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.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
|
9868 ng*h/mL
Standard Deviation 4930
|
17435 ng*h/mL
Standard Deviation 8772
|
SECONDARY outcome
Timeframe: Pre-dose on Day 14 and Day 28Population: 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.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=19 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Trough Plasma Concentration (Ctrough) of Simeprevir
|
3059 nanogram per Milliliters (ng/mL)
Standard Deviation 4236
|
8453 nanogram per Milliliters (ng/mL)
Standard Deviation 6455
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=19 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
|
6.00 hour (H)
Interval 4.0 to 12.0
|
6.00 hour (H)
Interval 0.47 to 10.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
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).
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=19 Participants
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.
|
|---|---|---|
|
Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
|
4196 ng/mL
Standard Deviation 4833
|
10139 ng/mL
Standard Deviation 6628
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg).
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=19 Participants
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.
|
|---|---|---|
|
Fluctuation Index (FI) of Simeprevir
|
144 percentage fluctuation
Standard Deviation 55.5
|
84.4 percentage fluctuation
Standard Deviation 36.5
|
SECONDARY outcome
Timeframe: Pre-dose on Day 14 and Day 28Population: 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.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=18 Participants
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.
|
|---|---|---|
|
Trough Plasma Concentration (Ctrough) of Ledipasvir
|
376 ng/mL
Standard Deviation 211
|
659 ng/mL
Standard Deviation 406
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=17 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
|
4.07 Hour
Interval 1.0 to 8.0
|
6.00 Hour
Interval 3.93 to 10.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
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).
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=17 Participants
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.
|
|---|---|---|
|
Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
|
411 ng/mL
Standard Deviation 207
|
725 ng/mL
Standard Deviation 364
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28Population: 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.
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax Cmin\]/Cavg).
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=17 Participants
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.
|
|---|---|---|
|
Fluctuation Index (FI) of Ledipasvir
|
60.6 percentage fluctuation
Standard Deviation 19.7
|
51.2 percentage fluctuation
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events
|
17 number of participants
|
15 number of participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Serious adverse events
|
2 number of participants
|
0 number of participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Percentage of Participants With On-treatment Virologic Response
Week 10: < 15 IU/mL undetectable/detectable
|
100.0 percentage of participants
|
NA percentage of participants
Week 10 is not applicable for Panel 2. The scheduled end of treatment visit for Panel 2 was Week 8.
|
|
Percentage of Participants With On-treatment Virologic Response
Week 1: >= 15 IU/mL
|
65.0 percentage of participants
|
60.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 1: < 15 IU/mL undetectable/detectable
|
35.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 1: < 15 IU/mL detectable
|
15.0 percentage of participants
|
35.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 1: < 15 IU/mL undetectable
|
20.0 percentage of participants
|
5.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 2: >= 15 IU/mL
|
25.0 percentage of participants
|
35.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 2: < 15 IU/mL undetectable/detectable
|
75.0 percentage of participants
|
65.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 2: < 15 IU/mL detectable
|
30.0 percentage of participants
|
30.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 2: < 15 IU/mL undetectable (vRVR)
|
45.0 percentage of participants
|
35.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 4: >= 15 IU/mL
|
0 percentage of participants
|
5.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 4: < 15 IU/mL undetectable/detectable
|
100.0 percentage of participants
|
95.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 4: < 15 IU/mL detectable
|
15.0 percentage of participants
|
5.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 4: < 15 IU/mL undetectable (RVR)
|
85.0 percentage of participants
|
90.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 6: >= 15 IU/mL
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 6: < 15 IU/mL undetectable/detectable
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 6: < 15 IU/mL detectable
|
0 percentage of participants
|
5.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 6: < 15 IU/mL undetectable
|
100.0 percentage of participants
|
95.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 8: >= 15 IU/mL
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 8: < 15 IU/mL undetectable/detectable
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 8: < 15 IU/mL detectable
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 8: < 15 IU/mL undetectable
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response
Week 10: >= 15 IU/mL
|
0 percentage of participants
|
NA percentage of participants
Week 10 is not applicable for Panel 2. The scheduled end of treatment visit for Panel 2 was Week 8.
|
|
Percentage of Participants With On-treatment Virologic Response
Week 10: < 15 IU/mL detectable
|
0 percentage of participants
|
NA percentage of participants
Week 10 is not applicable for Panel 2. The scheduled end of treatment visit for Panel 2 was Week 8.
|
|
Percentage of Participants With On-treatment Virologic Response
Week 10: < 15 IU/mL undetectable
|
100.0 percentage of participants
|
NA percentage of participants
Week 10 is not applicable for Panel 2. The scheduled end of treatment visit for Panel 2 was Week 8.
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
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
|
100 percentage of participants
|
|
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
|
100 percentage of participants
|
SECONDARY outcome
Timeframe: Day 70 in Panel 1 and Day 56 in Panel 2Population: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
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).
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Percentage of Participants With On-treatment Failure
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 12 follow-up phase after EOTPopulation: The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
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.
Outcome measures
| Measure |
Panel 1: SMV 150 mg + SOF 400 mg (Day 14)
n=20 Participants
Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
|
Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
n=20 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Viral Relapse
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2Population: 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.
Outcome measures
Outcome data not reported
Adverse Events
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Serious adverse events
| Measure |
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])
n=20 participants at risk
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.
|
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
n=20 participants at risk
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Fibula fracture
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
Other adverse events
| Measure |
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks])
n=20 participants at risk
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.
|
Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
n=20 participants at risk
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.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Eye disorders
Eye irritation
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Eye disorders
Photophobia
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Eye disorders
Vision blurred
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Abdominal distension
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Nausea
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
General disorders
Asthenia
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
General disorders
Catheter site paraesthesia
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
General disorders
Fatigue
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
General disorders
Peripheral swelling
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
General disorders
Pyrexia
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Hepatobiliary disorders
Jaundice
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Angular cheilitis
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Ear infection
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Genital abscess
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Laryngitis
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Nasopharyngitis
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Oral herpes
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Pneumonia
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Infections and infestations
Tooth infection
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Dizziness
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Dysgeusia
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
15.0%
3/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Nervous system disorders
Presyncope
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Psychiatric disorders
Depression
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Psychiatric disorders
Insomnia
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Reproductive system and breast disorders
Breast atrophy
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
55.0%
11/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
35.0%
7/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.0%
3/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
15.0%
3/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Purpura
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Vascular disorders
Hot flush
|
10.0%
2/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
|
Vascular disorders
Vasculitis
|
0.00%
0/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
5.0%
1/20 • Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER