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Trial record 24 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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ClinicalTrials.gov Identifier: NCT02421211
Recruitment Status : Completed
First Posted : April 20, 2015
Results First Posted : January 5, 2017
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Hepatitis C, Chronic
Interventions Drug: Simeprevir (SMV)
Drug: Ledipasvir (LDV)
Drug: Sofosbuvir (SOF)
Enrollment 41
Recruitment Details  
Pre-assignment Details A total of 41 participants were enrolled in the study, among them 40 participants (20 per panel) were randomized and treated. One participant was early terminated from the study, due to withdrawal of consent before randomization to study drug. All randomized participants received study drug and were included in the intent to treat (ITT) population.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 20 20
Completed 20 20
Not Completed 0 0
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 20 20 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 20 participants 20 participants 40 participants
50.5
(25 to 70)
51
(26 to 62)
51
(25 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
Female
12
  60.0%
10
  50.0%
22
  55.0%
Male
8
  40.0%
10
  50.0%
18
  45.0%
1.Primary Outcome
Title Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
Hide Description The Cmin is the minimum observed plasma concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: nanogram per Milliliters (ng/mL)
2411  (3778) 6701  (4179)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 1: SMV 150 mg + SOF 400 mg (Day 14), Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 4.7
Confidence Interval (2-Sided) 90%
3.4 to 6.5
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Simeprevir
Hide Description The Cmax is the maximum observed plasma concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
6767  (6362) 13691  (7775)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 1: SMV 150 mg + SOF 400 mg (Day 14), Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 2.3
Confidence Interval (2-Sided) 90%
2.0 to 2.8
Estimation Comments [Not Specified]
3.Primary Outcome
Title Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
Hide Description The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: nanogram hour per Milliliters (ng*h/mL)
100492  (115868) 243564  (159124)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 1: SMV 150 mg + SOF 400 mg (Day 14), Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 3.1
Confidence Interval (2-Sided) 90%
2.4 to 3.8
Estimation Comments [Not Specified]
4.Primary Outcome
Title Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
Hide Description The Cmin is the minimum observed plasma concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
319  (178) 557  (307)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 2: LDV 90mg/SOF 400mg (Day 14), Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 1.7
Confidence Interval (2-Sided) 90%
1.5 to 2.0
Estimation Comments [Not Specified]
5.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Ledipasvir
Hide Description The Cmax is the maximum observed plasma concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: ng/mL
556  (270) 930  (466)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 2: LDV 90mg/SOF 400mg (Day 14), Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 1.6
Confidence Interval (2-Sided) 90%
1.4 to 1.9
Estimation Comments [Not Specified]
6.Primary Outcome
Title Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
Hide Description AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
9868  (4930) 17435  (8772)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Panel 2: LDV 90mg/SOF 400mg (Day 14), Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means ratio
Estimated Value 1.7
Confidence Interval (2-Sided) 90%
1.6 to 2.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Simeprevir
Hide Description The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Time Frame Pre-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 19 20
Mean (Standard Deviation)
Unit of Measure: nanogram per Milliliters (ng/mL)
3059  (4236) 8453  (6455)
8.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
Hide Description The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 19
Median (Full Range)
Unit of Measure: hour (H)
6.00
(4.00 to 12.00)
6.00
(0.47 to 10.00)
9.Secondary Outcome
Title Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
Hide Description The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
4196  (4833) 10139  (6628)
10.Secondary Outcome
Title Fluctuation Index (FI) of Simeprevir
Hide Description Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 1: SMV 150 mg + SOF 400 mg (Day 14) Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: percentage fluctuation
144  (55.5) 84.4  (36.5)
11.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Ledipasvir
Hide Description The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Time Frame Pre-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
376  (211) 659  (406)
12.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
Hide Description The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 17
Median (Full Range)
Unit of Measure: Hour
4.07
(1.00 to 8.00)
6.00
(3.93 to 10.00)
13.Secondary Outcome
Title Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
Hide Description The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: ng/mL
411  (207) 725  (364)
14.Secondary Outcome
Title Fluctuation Index (FI) of Ledipasvir
Hide Description Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Time Frame Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF. Here, “Number of Participants Analyzed” signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Panel 2: LDV 90mg/SOF 400mg (Day 14) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)
Hide Arm/Group Description:
Participants received 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 Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: percentage fluctuation
60.6  (19.7) 51.2  (0.17)
15.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: number of participants
Adverse events 17 15
Serious adverse events 2 0
16.Secondary Outcome
Title Percentage of Participants With On-treatment Virologic Response
Hide Description

On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.

The following thresholds were considered at any time point: less than (<) lower limit of quantification (LLOQ) undetectable, <LLOQ detectable and <LLOQ undetectable/detectable.

Time Frame Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of participants
Week 1: >= 15 IU/mL 65.0 60.0
Week 1: < 15 IU/mL undetectable/detectable 35.0 40.0
Week 1: < 15 IU/mL detectable 15.0 35.0
Week 1: < 15 IU/mL undetectable 20.0 5.0
Week 2: >= 15 IU/mL 25.0 35.0
Week 2: < 15 IU/mL undetectable/detectable 75.0 65.0
Week 2: < 15 IU/mL detectable 30.0 30.0
Week 2: < 15 IU/mL undetectable (vRVR) 45.0 35.0
Week 4: >= 15 IU/mL 0 5
Week 4: < 15 IU/mL undetectable/detectable 100.0 95.0
Week 4: < 15 IU/mL detectable 15.0 5.0
Week 4: < 15 IU/mL undetectable (RVR) 85.0 90.0
Week 6: >= 15 IU/mL 0 0
Week 6: < 15 IU/mL undetectable/detectable 100.0 100.0
Week 6: < 15 IU/mL detectable 0 5
Week 6: < 15 IU/mL undetectable 100.0 95.0
Week 8: >= 15 IU/mL 0 0
Week 8: < 15 IU/mL undetectable/detectable 100.0 100.0
Week 8: < 15 IU/mL detectable 0 0
Week 8: < 15 IU/mL undetectable 100.0 100.0
Week 10: >= 15 IU/mL 0 NA [1] 
Week 10: < 15 IU/mL undetectable/detectable 100.0 NA [1] 
Week 10: < 15 IU/mL detectable 0 NA [1] 
Week 10: < 15 IU/mL undetectable 100.0 NA [1] 
[1]
Week 10 is not applicable for Panel 2. The scheduled end of treatment visit for Panel 2 was Week 8.
17.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)
Hide Description SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA <LLOQ detectable or undetectable.
Time Frame 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of participants
SVR4 100 100
SVR12 100 100
18.Secondary Outcome
Title Percentage of Participants With On-treatment Failure
Hide Description On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <LLOQ while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to AEs, withdrawal of consent).
Time Frame Day 70 in Panel 1 and Day 56 in Panel 2
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Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of participants
0 0
19.Secondary Outcome
Title Percentage of Participants With Viral Relapse
Hide Description Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.
Time Frame Up to Week 12 follow-up phase after EOT
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of participants
0 0
20.Secondary Outcome
Title Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence
Hide Description [Not Specified]
Time Frame Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description:
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.
Participants received 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 Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious 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)
Affected / at Risk (%) Affected / at Risk (%)
Total   2/20 (10.00%)   0/20 (0.00%) 
Injury, poisoning and procedural complications     
Fibula fracture * 1  1/20 (5.00%)  0/20 (0.00%) 
Tibia fracture * 1  1/20 (5.00%)  0/20 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)
Affected / at Risk (%) Affected / at Risk (%)
Total   17/20 (85.00%)   15/20 (75.00%) 
Ear and labyrinth disorders     
Vertigo * 1  0/20 (0.00%)  1/20 (5.00%) 
Eye disorders     
Eye irritation * 1  1/20 (5.00%)  0/20 (0.00%) 
Eyelid oedema * 1  0/20 (0.00%)  1/20 (5.00%) 
Photophobia * 1  1/20 (5.00%)  0/20 (0.00%) 
Vision blurred * 1  1/20 (5.00%)  0/20 (0.00%) 
Gastrointestinal disorders     
Abdominal distension * 1  1/20 (5.00%)  0/20 (0.00%) 
Abdominal pain upper * 1  2/20 (10.00%)  1/20 (5.00%) 
Constipation * 1  1/20 (5.00%)  0/20 (0.00%) 
Diarrhoea * 1  2/20 (10.00%)  0/20 (0.00%) 
Dyspepsia * 1  1/20 (5.00%)  0/20 (0.00%) 
Flatulence * 1  0/20 (0.00%)  1/20 (5.00%) 
Nausea * 1  1/20 (5.00%)  0/20 (0.00%) 
Vomiting * 1  2/20 (10.00%)  0/20 (0.00%) 
General disorders     
Asthenia * 1  2/20 (10.00%)  1/20 (5.00%) 
Catheter site paraesthesia * 1  1/20 (5.00%)  0/20 (0.00%) 
Fatigue * 1  2/20 (10.00%)  1/20 (5.00%) 
Peripheral swelling * 1  1/20 (5.00%)  0/20 (0.00%) 
Pyrexia * 1  2/20 (10.00%)  0/20 (0.00%) 
Hepatobiliary disorders     
Jaundice * 1  1/20 (5.00%)  0/20 (0.00%) 
Infections and infestations     
Angular cheilitis * 1  1/20 (5.00%)  0/20 (0.00%) 
Ear infection * 1  1/20 (5.00%)  0/20 (0.00%) 
Genital abscess * 1  1/20 (5.00%)  0/20 (0.00%) 
Laryngitis * 1  1/20 (5.00%)  0/20 (0.00%) 
Nasopharyngitis * 1  1/20 (5.00%)  0/20 (0.00%) 
Oral herpes * 1  0/20 (0.00%)  1/20 (5.00%) 
Pneumonia * 1  1/20 (5.00%)  0/20 (0.00%) 
Tooth infection * 1  0/20 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/20 (5.00%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/20 (0.00%)  2/20 (10.00%) 
Muscle spasms * 1  1/20 (5.00%)  0/20 (0.00%) 
Nervous system disorders     
Disturbance in attention * 1  0/20 (0.00%)  1/20 (5.00%) 
Dizziness * 1  1/20 (5.00%)  0/20 (0.00%) 
Dysgeusia * 1  2/20 (10.00%)  0/20 (0.00%) 
Headache * 1  1/20 (5.00%)  3/20 (15.00%) 
Paraesthesia * 1  0/20 (0.00%)  2/20 (10.00%) 
Presyncope * 1  0/20 (0.00%)  1/20 (5.00%) 
Psychiatric disorders     
Depression * 1  1/20 (5.00%)  0/20 (0.00%) 
Insomnia * 1  1/20 (5.00%)  1/20 (5.00%) 
Reproductive system and breast disorders     
Breast atrophy * 1  1/20 (5.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/20 (10.00%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  0/20 (0.00%)  1/20 (5.00%) 
Eczema * 1  1/20 (5.00%)  0/20 (0.00%) 
Erythema * 1  0/20 (0.00%)  2/20 (10.00%) 
Hyperhidrosis * 1  0/20 (0.00%)  1/20 (5.00%) 
Photosensitivity reaction * 1  11/20 (55.00%)  7/20 (35.00%) 
Pruritus * 1  3/20 (15.00%)  3/20 (15.00%) 
Purpura * 1  1/20 (5.00%)  1/20 (5.00%) 
Rash * 1  1/20 (5.00%)  0/20 (0.00%) 
Vascular disorders     
Hot flush * 1  2/20 (10.00%)  1/20 (5.00%) 
Vasculitis * 1  0/20 (0.00%)  1/20 (5.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Physician, Clinical Development
Organization: Janssen Research & Development
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT02421211     History of Changes
Other Study ID Numbers: CR106992
TMC435HPC2017 ( Other Identifier: Janssen Sciences Ireland UC )
2015-000459-25 ( EudraCT Number )
First Submitted: April 15, 2015
First Posted: April 20, 2015
Results First Submitted: November 7, 2016
Results First Posted: January 5, 2017
Last Update Posted: March 28, 2019