Hepatitis C
Conditions
Keywords
Hepatitis C, TMC435
Brief summary
The purpose of this study is to assess anti-viral activity (inhibition of viral growth) of TMC435350 in genotype 2,3,4,5 and 6 hepatitis C virus infected participants who have never received treatment for their hepatitis C infection.
Detailed description
This is an open-label (all people know the identity of the intervention) study to assess the antiviral activity, safety, tolerability and pharmacokinetics (explores what the body does to the medication) of TMC435350 hereafter referred to as TMC435. Approximately 40 participants will be divided in 5 groups as per the genotype (8 participants each group). The study will include a screening phase (up to 6 weeks), treatment phase (7 days) and a follow-up phase (30-35 days after the last dose of study medication). Safety evaluations will include assessment of adverse events, clinical laboratory tests and cardiovascular safety.
Interventions
DRUGTMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Sponsors
Tibotec Pharmaceuticals, Ireland
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants with documented chronic genotype 2, 3, 4, 5 or 6 hepatitis C virus (HCV) infection * Participants who have never received treatment for their HCV infection * Participants with either no cirrhosis or up to Child Pugh A liver disease * Participants with plasma HCV genotype level of more than or equal to 100, 000 IU/mL at screening
Exclusion criteria
* Evidence of Child Pugh B or C liver disease at screening, decompensated liver disease defined as prior or current history of ascities, hepatic encephalopathy, esophageal or gastric varices * Participants with diagnosed or suspected hepatocellular carcinoma * Participants coinfected with human immunodeficiency virus type 1 or 2, or hepatitis A or B virus infection or active tuberculosis at screening * Participants with any active clinically significant disease, or medical history or physical examination or electrocardiogram findings during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Baseline, Day 3, and Day 7 | The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Baseline, Day 3, Day 5 and Day 7 | The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period. |
| Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Baseline, Day 3, Day 5 and Day 7 | The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period. |
| Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | During the 7-day of TMC435 treatment period | The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable \[less than 25 IU/mL undetectable\] or not quantifiable \[less than 25 IU/mL detectable\]) during the 7-day TMC435 treatment period. |
| Predose Plasma Concentration (C0h) of TMC435 | Predose on Day 7 | The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period. |
| Minimum Plasma Concentration (Cmin) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period. |
| Maximum Plasma Concentration (Cmax) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment. |
| Average Steady-State Plasma Concentration (Css,av) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period. |
| Fluctuation Index (FI) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection. |
| Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection. |
| Elimination Rate Constant of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection. |
| Terminal Elimination Half-life (t1/2,Term) of TMC435 | Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7 | The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration. |
Countries
Belgium, Germany, Thailand
Participant flow
Recruitment details
A total of 37 participants from 3 countries were enrolled and started treatment in the study (17 participants in Belgium, 12 participants in Germany, and 8 participants in Thailand).
Pre-assignment details
A total of 48 participants were screened of which 11 participants were not treated with TMC435. A total of 37 participants received study medication.
Participants by arm
| Arm | Count |
|---|---|
| Genotype 2 Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | 6 |
| Genotype 3 Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | 8 |
| Genotype 4 Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | 8 |
| Genotype 5 Participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | 7 |
| Genotype 6 Participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days | 8 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 5 | Genotype 6 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 43 years | 42 years | 47 years | 65 years | 49 years | 48 years |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 8 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 7 Participants | 6 Participants | 7 Participants | 0 Participants | 25 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 6 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 37 |
| serious Total, serious adverse events | 1 / 37 |
Outcome results
Primary
Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period.
Time frame: Baseline, Day 3, and Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotype 2 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 3 | -2.02 log10 IU/mL | Standard Error 0.625 |
| Genotype 2 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 7 | -2.46 log10 IU/mL | Standard Error 0.538 |
| Genotype 3 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 3 | 0.16 log10 IU/mL | Standard Error 0.263 |
| Genotype 3 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 7 | -0.13 log10 IU/mL | Standard Error 0.175 |
| Genotype 4 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 3 | -3.43 log10 IU/mL | Standard Error 0.167 |
| Genotype 4 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 7 | -3.66 log10 IU/mL | Standard Error 0.32 |
| Genotype 5 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 7 | -2.43 log10 IU/mL | Standard Error 0.357 |
| Genotype 5 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 3 | -2.71 log10 IU/mL | Standard Error 0.335 |
| Genotype 6 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 3 | -3.57 log10 IU/mL | Standard Error 0.197 |
| Genotype 6 | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels | Day 7 | -4.40 log10 IU/mL | Standard Error 0.222 |
Secondary
Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435
The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - as all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | 170100 ng*h/mL |
| Genotype 3 | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | 74670 ng*h/mL |
| Genotype 4 | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | 212000 ng*h/mL |
| Genotype 5 | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | 189000 ng*h/mL |
| Genotype 6 | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 | 227100 ng*h/mL |
Secondary
Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435
The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | 268000 ng*h/mL |
| Genotype 3 | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | 111500 ng*h/mL |
| Genotype 4 | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | 365500 ng*h/mL |
| Genotype 5 | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | 360000 ng*h/mL |
| Genotype 6 | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 | 411100 ng*h/mL |
Secondary
Average Steady-State Plasma Concentration (Css,av) of TMC435
The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Average Steady-State Plasma Concentration (Css,av) of TMC435 | 7115 ng/mL |
| Genotype 3 | Average Steady-State Plasma Concentration (Css,av) of TMC435 | 3081 ng/mL |
| Genotype 4 | Average Steady-State Plasma Concentration (Css,av) of TMC435 | 8843 ng/mL |
| Genotype 5 | Average Steady-State Plasma Concentration (Css,av) of TMC435 | 7850 ng/mL |
| Genotype 6 | Average Steady-State Plasma Concentration (Css,av) of TMC435 | 9354 ng/mL |
Secondary
Elimination Rate Constant of TMC435
In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Elimination Rate Constant of TMC435 | 0.05042 1/hour |
| Genotype 3 | Elimination Rate Constant of TMC435 | 0.06024 1/hour |
| Genotype 4 | Elimination Rate Constant of TMC435 | 0.04308 1/hour |
| Genotype 5 | Elimination Rate Constant of TMC435 | 0.03826 1/hour |
| Genotype 6 | Elimination Rate Constant of TMC435 | 0.03784 1/hour |
Secondary
Fluctuation Index (FI) of TMC435
The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Fluctuation Index (FI) of TMC435 | 130.2 % fluctuation |
| Genotype 3 | Fluctuation Index (FI) of TMC435 | 149.4 % fluctuation |
| Genotype 4 | Fluctuation Index (FI) of TMC435 | 95.38 % fluctuation |
| Genotype 5 | Fluctuation Index (FI) of TMC435 | 93.12 % fluctuation |
| Genotype 6 | Fluctuation Index (FI) of TMC435 | 88.16 % fluctuation |
Secondary
Maximum Plasma Concentration (Cmax) of TMC435
The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Maximum Plasma Concentration (Cmax) of TMC435 | 11250 ng/mL |
| Genotype 3 | Maximum Plasma Concentration (Cmax) of TMC435 | 6580 ng/mL |
| Genotype 4 | Maximum Plasma Concentration (Cmax) of TMC435 | 13500 ng/mL |
| Genotype 5 | Maximum Plasma Concentration (Cmax) of TMC435 | 13600 ng/mL |
| Genotype 6 | Maximum Plasma Concentration (Cmax) of TMC435 | 14800 ng/mL |
Secondary
Minimum Plasma Concentration (Cmin) of TMC435
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Minimum Plasma Concentration (Cmin) of TMC435 | 3320 ng/mL |
| Genotype 3 | Minimum Plasma Concentration (Cmin) of TMC435 | 1110 ng/mL |
| Genotype 4 | Minimum Plasma Concentration (Cmin) of TMC435 | 5450 ng/mL |
| Genotype 5 | Minimum Plasma Concentration (Cmin) of TMC435 | 4230 ng/mL |
| Genotype 6 | Minimum Plasma Concentration (Cmin) of TMC435 | 4960 ng/mL |
Secondary
Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable \[less than 25 IU/mL undetectable\] or not quantifiable \[less than 25 IU/mL detectable\]) during the 7-day TMC435 treatment period.
Time frame: During the 7-day of TMC435 treatment period
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 2 | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | 0 Participants |
| Genotype 3 | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | 1 Participants |
| Genotype 4 | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | 2 Participants |
| Genotype 5 | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | 3 Participants |
| Genotype 6 | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period | 0 Participants |
Secondary
Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period
The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period.
Time frame: Baseline, Day 3, Day 5 and Day 7
Population: Intent-to-treat (ITT) Population- all randomized subjects who received at least 1 dose of study medication (TMC435)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotype 2 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 7 | 3 Participants |
| Genotype 2 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 5 | 3 Participants |
| Genotype 2 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 3 | 3 Participants |
| Genotype 3 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 7 | 0 Participants |
| Genotype 3 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 5 | 0 Participants |
| Genotype 3 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 3 | 0 Participants |
| Genotype 4 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 3 | 8 Participants |
| Genotype 4 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 7 | 8 Participants |
| Genotype 4 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 5 | 8 Participants |
| Genotype 5 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 3 | 6 Participants |
| Genotype 5 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 5 | 5 Participants |
| Genotype 5 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 7 | 5 Participants |
| Genotype 6 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 5 | 8 Participants |
| Genotype 6 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 7 | 8 Participants |
| Genotype 6 | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period | Day 3 | 8 Participants |
Secondary
Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period
The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period.
Time frame: Baseline, Day 3, Day 5 and Day 7
Population: Intent-to-treat (ITT) Population - all randomized subjects who received at least 1 dose of study medication (TMC435)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL) | 0 Participants |
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL) | 0 Participants |
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL) | 0 Participants |
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 2 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL) | 0 Participants |
| Genotype 3 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL) | 0 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL) | 0 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL) | 2 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL undetectable) | 1 Participants |
| Genotype 4 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL) | 3 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL) | 0 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL) | 0 Participants |
| Genotype 5 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL) | 0 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL) | 1 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 7 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL) | 0 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL) | 1 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 5 (less than 25 IU/mL undetectable) | 0 Participants |
| Genotype 6 | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period | Day 3 (less than 25 IU/mL undetectable) | 0 Participants |
Secondary
Predose Plasma Concentration (C0h) of TMC435
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.
Time frame: Predose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Predose Plasma Concentration (C0h) of TMC435 | 3720 ng/mL |
| Genotype 3 | Predose Plasma Concentration (C0h) of TMC435 | 1310 ng/mL |
| Genotype 4 | Predose Plasma Concentration (C0h) of TMC435 | 6270 ng/mL |
| Genotype 5 | Predose Plasma Concentration (C0h) of TMC435 | 4650 ng/mL |
| Genotype 6 | Predose Plasma Concentration (C0h) of TMC435 | 5440 ng/mL |
Secondary
Terminal Elimination Half-life (t1/2,Term) of TMC435
The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Terminal Elimination Half-life (t1/2,Term) of TMC435 | 13.75 hours |
| Genotype 3 | Terminal Elimination Half-life (t1/2,Term) of TMC435 | 11.51 hours |
| Genotype 4 | Terminal Elimination Half-life (t1/2,Term) of TMC435 | 16.09 hours |
| Genotype 5 | Terminal Elimination Half-life (t1/2,Term) of TMC435 | 18.12 hours |
| Genotype 6 | Terminal Elimination Half-life (t1/2,Term) of TMC435 | 18.32 hours |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment.
Time frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genotype 2 | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | 4.01 hours |
| Genotype 3 | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | 6.025 hours |
| Genotype 4 | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | 6.04 hours |
| Genotype 5 | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | 6.00 hours |
| Genotype 6 | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 | 6.00 hours |