A Study to Investigate the Pharmacokinetic Interactions B... | NCT02421211

NCT02421211

ID	Type	Description	Link
TMC435HPC2017	Other Identifier	Janssen Sciences Ireland UC
2015-000459-25	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Panel 1	Experimental	Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.	Drug: Simeprevir (SMV) Drug: Ledipasvir (LDV) Drug: Sofosbuvir (SOF)
Panel 2	Experimental	Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.	Drug: Simeprevir (SMV) Drug: Ledipasvir (LDV) Drug: Sofosbuvir (SOF)

Name	Type	Description	Arm Group Labels	Other Names
Simeprevir (SMV)	Drug	Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.	Panel 1 Panel 2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)	The Cmin is the minimum observed plasma concentration.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Maximum Plasma Concentration (Cmax) of Simeprevir	The Cmax is the maximum observed plasma concentration.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir	The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)	The Cmin is the minimum observed plasma concentration.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Maximum Plasma Concentration (Cmax) of Ledipasvir	The Cmax is the maximum observed plasma concentration.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir	AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

Secondary Outcomes

Measure	Description	Time Frame
Trough Plasma Concentration (Ctrough) of Simeprevir	The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.	Pre-dose on Day 14 and Day 28
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants with Body Mass Index (weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter kg/m^2, extremes included
Participants must be treatment-naive (that is, have not received prior treatment with any approved or investigational drug)
Participants with HCV ribonucleic acid (RNA) plasma levels greater than (>) 10,000 international unit per milliliter (IU/ml) and lower than 6,000,000 international unit per milliliter (IU/ml) at screening
Participants with absence of cirrhosis confirmed by FibroTest/Fibrosure score less or equal to 0.75 and an aspartate aminotransferase to platelet ration index less or equal to 2 or a Fibroscan less or equal to 14.6 kilopascale (kPA), performed within 6 months prior or during the screening period
Participants with documented chronic HCV infection: diagnosis of HCV infection >6 months prior to screening, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes consistent with chronic hepatitis in a liver biopsy

Exclusion Criteria:

Participant has infection/co-infection with HCV of a genotype other than genotype 1, human immunodeficiency virus (HIV) type 1 or 2
Participant has any evidence of liver disease of non-HCV etiology. This includes, but is not limited to acute hepatitis A, active hepatitis B, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HC liver disease considered clinically significant by the investigator
Participant with significant co-morbidities, conditions or clinical significant findings during screening assessments that in the opinion of the investigator could compromise the participants' safety or could interfere with the Participant participating in and completing the study
Participant received an organ transplant (other than cornea or hair transplant or skin graft)
Participants have key protocol defined laboratory abnormalities

Contacts/Locations Module

Name	Affiliation	Role
Janssen Sciences Ireland UC Clinical Trial	Janssen Sciences Ireland UC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28971875	Derived	Bourgeois S, Horsmans Y, Nevens F, van Vlierberghe H, Moreno C, Beumont M, Vijgen L, van Eygen V, Luo D, Hillewaert V, Van Remoortere P, van de Logt J, Ouwerkerk-Mahadevan S. Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01217-17. doi: 10.1128/AAC.01217-17. Print 2017 Dec.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00120 BG00240

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	OG0002411± 3778 OG0016701± 4179

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						LS means ratio	4.7			2-Sided	90	3.4	6.5					Superiority or Other

Primary

Maximum Plasma Concentration (Cmax) of Simeprevir

The Cmax is the maximum observed plasma concentration.

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.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants	OG000

Primary

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir

The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

Posted

Mean

Standard Deviation

nanogram hour per Milliliters (ng*h/mL)

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Primary

Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)

The Cmin is the minimum observed plasma concentration.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants	OG000

Primary

Maximum Plasma Concentration (Cmax) of Ledipasvir

The Cmax is the maximum observed plasma concentration.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants	OG000

Primary

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir

AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.

Posted

Mean

Standard Deviation

ng*h/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Trough Plasma Concentration (Ctrough) of Simeprevir

The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.

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.

Posted

Mean

Standard Deviation

nanogram per Milliliters (ng/mL)

Pre-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

Posted

Median

Full Range

hour (H)

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir

The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Fluctuation Index (FI) of Simeprevir

Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).

Posted

Mean

Standard Deviation

percentage fluctuation

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 1: SMV 150 mg + SOF 400 mg (Day 14)	Participants received simeprevir (SMV) 150 milligram (mg) capsule and sofosbuvir (SOF) 400 mg tablet, orally, once daily from Day 1 until Day 14.
OG001	Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Trough Plasma Concentration (Ctrough) of Ledipasvir

The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants	OG000

Secondary

Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

Posted

Median

Full Range

Hour

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants	OG000

Secondary

Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir

The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Fluctuation Index (FI) of Ledipasvir

Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).

Posted

Mean

Standard Deviation

percentage fluctuation

Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

ID	Title	Description
OG000	Panel 2: LDV 90mg/SOF 400mg (Day 14)	Participants received FDC tablet of 90 mg LDV/400 mg SOF, orally, once daily from Day 1 until Day 14.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28)	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.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Posted

Number

number of participants

Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Secondary

Percentage of Participants With On-treatment Virologic Response

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

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

The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Posted

Number

percentage of participants

Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Secondary

Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)

SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA \

The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Posted

Number

percentage of participants

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)

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Secondary

Percentage of Participants With On-treatment Failure

On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been \

The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Posted

Number

percentage of participants

Day 70 in Panel 1 and Day 56 in Panel 2

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Secondary

Percentage of Participants With Viral Relapse

Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.

The ITT analysis set is defined as all participants who took at least 1 dose of SMV, LDV, or SOF.

Posted

Number

percentage of participants

Up to Week 12 follow-up phase after EOT

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Units	Counts

Secondary

Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence

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.

Posted

Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2

ID	Title	Description
OG000	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.
OG001	Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks)	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			2	20	17	20
EG001	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.			0	20	15	20

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Fibula fracture	Injury, poisoning and procedural complications	MedDRA Version 17.1	Non-systematic Assessment		EG0001 affected20 at risk EG0010 affected20 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA Version 17.1	Non-systematic Assessment		EG0001 affected20 at risk EG0010 affected20 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Eye irritation	Eye disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Eyelid oedema	Eye disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Photophobia	Eye disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Vision blurred	Eye disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Flatulence	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Asthenia	General disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Catheter site paraesthesia	General disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Fatigue	General disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Peripheral swelling	General disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Pyrexia	General disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Jaundice	Hepatobiliary disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Angular cheilitis	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Ear infection	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Genital abscess	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Laryngitis	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Oral herpes	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pneumonia	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Tooth infection	Infections and infestations	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Disturbance in attention	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Dizziness	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Headache	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Presyncope	Nervous system disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Depression	Psychiatric disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Insomnia	Psychiatric disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Breast atrophy	Reproductive system and breast disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG00011 affected20 at risk EG0017 affected20 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0003 affected20 at risk EG0013 affected20 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Hot flush	Vascular disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Vasculitis	Vascular disorders	MedDRA Version 17.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk

ID	Term
D019698	Hepatitis C, Chronic

Ancestor Terms

ID	Term
D006526	Hepatitis C
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000069616	Simeprevir
C586541	ledipasvir
D000069474	Sofosbuvir

Ancestor Terms

ID	Term
D013449	Sulfonamides
D013450	Sulfones
D013457	Sulfur Compounds
D009930	Organic Chemicals
D006575	Heterocyclic Compounds, 3-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D014542	Uridine Monophosphate
D014500	Uracil Nucleotides
D011742	Pyrimidine Nucleotides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D009711	Nucleotides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012265	Ribonucleotides

Units	Counts
Participants	OG00020 OG00120

Units	Counts
Participants	OG00020 OG00120

Units	Counts
Participants	OG00020 OG00120

Facility	Status	City	State	ZIP	Country	Contacts
		Antwerp			Belgium