Trial Outcomes & Findings for A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV) (NCT NCT00812331)
NCT ID: NCT00812331
Last Updated: 2014-07-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Baseline, Day 3, and Day 7
Results posted on
2014-07-28
Participant Flow
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).
A total of 48 participants were screened of which 11 participants were not treated with TMC435. A total of 37 participants received study medication.
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
8
|
7
|
8
|
|
Overall Study
COMPLETED
|
5
|
8
|
8
|
7
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
Baseline characteristics by cohort
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
Genotype 5
n=7 Participants
Participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
Genotype 6
n=8 Participants
Participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
|
Age, Continuous
|
43 years
n=5 Participants
|
42 years
n=7 Participants
|
47 years
n=5 Participants
|
65 years
n=4 Participants
|
49 years
n=21 Participants
|
48 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
18 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
19 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
25 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 3, and Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
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 • Interval -3.6 to -0.3
|
0.16 log10 IU/mL
Standard Error 0.263 • Interval -0.7 to 1.8
|
-3.43 log10 IU/mL
Standard Error 0.167 • Interval -3.9 to -2.6
|
-2.71 log10 IU/mL
Standard Error 0.335 • Interval -4.0 to -1.5
|
-3.57 log10 IU/mL
Standard Error 0.197 • Interval -4.2 to -2.7
|
|
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 • Interval -4.2 to -0.9
|
-0.13 log10 IU/mL
Standard Error 0.175 • Interval -1.0 to 0.6
|
-3.66 log10 IU/mL
Standard Error 0.320 • Interval -4.7 to -2.3
|
-2.43 log10 IU/mL
Standard Error 0.357 • Interval -3.2 to -0.7
|
-4.40 log10 IU/mL
Standard Error 0.222 • Interval -5.2 to -3.3
|
SECONDARY outcome
Timeframe: Baseline, Day 3, Day 5 and Day 7Population: Intent-to-treat (ITT) Population- all randomized subjects who received at least 1 dose of study medication (TMC435)
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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
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
|
0 Participants
|
8 Participants
|
6 Participants
|
8 Participants
|
|
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
|
0 Participants
|
8 Participants
|
5 Participants
|
8 Participants
|
|
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
|
0 Participants
|
8 Participants
|
5 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 3, Day 5 and Day 7Population: Intent-to-treat (ITT) Population - all randomized subjects who received at least 1 dose of study medication (TMC435)
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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
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
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: During the 7-day of TMC435 treatment periodPopulation: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
|
0 Participants
|
1 Participants
|
2 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Predose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Predose Plasma Concentration (C0h) of TMC435
|
3720 ng/mL
Interval 164.0 to 8420.0
|
1310 ng/mL
Interval 492.0 to 4220.0
|
6270 ng/mL
Interval 1030.0 to 13100.0
|
4650 ng/mL
Interval 80.1 to 14500.0
|
5440 ng/mL
Interval 2280.0 to 11700.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC435).
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Minimum Plasma Concentration (Cmin) of TMC435
|
3320 ng/mL
Interval 156.0 to 8420.0
|
1110 ng/mL
Interval 463.0 to 3440.0
|
5450 ng/mL
Interval 1030.0 to 13100.0
|
4230 ng/mL
Interval 48.2 to 14300.0
|
4960 ng/mL
Interval 2080.0 to 10600.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of TMC435
|
11250 ng/mL
Interval 2360.0 to 18500.0
|
6580 ng/mL
Interval 2760.0 to 13200.0
|
13500 ng/mL
Interval 4530.0 to 26200.0
|
13600 ng/mL
Interval 215.0 to 24700.0
|
14800 ng/mL
Interval 3460.0 to 23000.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
|
4.01 hours
Interval 4.0 to 7.83
|
6.025 hours
Interval 4.02 to 10.08
|
6.04 hours
Interval 4.0 to 8.08
|
6.00 hours
Interval 4.0 to 8.02
|
6.00 hours
Interval 4.0 to 6.2
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Average Steady-State Plasma Concentration (Css,av) of TMC435
|
7115 ng/mL
Interval 1110.0 to 12870.0
|
3081 ng/mL
Interval 1410.0 to 7550.0
|
8843 ng/mL
Interval 2954.0 to 20340.0
|
7850 ng/mL
Interval 130.8 to 19660.0
|
9354 ng/mL
Interval 2602.0 to 16180.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Fluctuation Index (FI) of TMC435
|
130.2 % fluctuation
Interval 78.35 to 210.4
|
149.4 % fluctuation
Interval 100.3 to 246.3
|
95.38 % fluctuation
Interval 56.77 to 161.1
|
93.12 % fluctuation
Interval 52.91 to 129.3
|
88.16 % fluctuation
Interval 53.04 to 127.6
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - as all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
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
Interval 26350.0 to 311000.0
|
74670 ng*h/mL
Interval 34500.0 to 199500.0
|
212000 ng*h/mL
Interval 70400.0 to 483000.0
|
189000 ng*h/mL
Interval 3084.0 to 457600.0
|
227100 ng*h/mL
Interval 63430.0 to 373500.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
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
Interval 31400.0 to 712600.0
|
111500 ng*h/mL
Interval 43680.0 to 272000.0
|
365500 ng*h/mL
Interval 99320.0 to 1179000.0
|
360000 ng*h/mL
Interval 3770.0 to 944400.0
|
411100 ng*h/mL
Interval 117500.0 to 798900.0
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Elimination Rate Constant of TMC435
|
0.05042 1/hour
Interval 0.01776 to 0.08666
|
0.06024 1/hour
Interval 0.04057 to 0.08552
|
0.04308 1/hour
Interval 0.01803 to 0.06955
|
0.03826 1/hour
Interval 0.03315 to 0.07737
|
0.03784 1/hour
Interval 0.01826 to 0.05926
|
SECONDARY outcome
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (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.
Outcome measures
| Measure |
Genotype 2
n=6 Participants
Participants with chronic genotype 2 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 3
n=8 Participants
Participants with chronic genotype 3 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 4
n=8 Participants
Participants with chronic genotype 4 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 5
n=7 Participants
participants with chronic genotype 5 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
Genotype 6
n=8 Participants
participants with chronic genotype 6 HCV infection who received 200 mg TMC435 as a single oral ((by mouth) dose once daily for 7 days.
|
|---|---|---|---|---|---|
|
Terminal Elimination Half-life (t1/2,Term) of TMC435
|
13.75 hours
Interval 7.998 to 39.04
|
11.51 hours
Interval 8.105 to 17.09
|
16.09 hours
Interval 9.966 to 38.44
|
18.12 hours
Interval 8.959 to 20.91
|
18.32 hours
Interval 11.7 to 37.95
|
Adverse Events
Total
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Total
n=37 participants at risk
Participants with chronic genotype 2,3,4,5 or 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
|---|---|
|
Gastrointestinal disorders
Ileitis
|
2.7%
1/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
Other adverse events
| Measure |
Total
n=37 participants at risk
Participants with chronic genotype 2,3,4,5 or 6 HCV infection who received 200 mg TMC435 as a single oral (by mouth) dose once daily for 7 days
|
|---|---|
|
General disorders
Influenza like illness
|
24.3%
9/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
General disorders
Fatigue
|
10.8%
4/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
General disorders
Pyrexia
|
5.4%
2/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.8%
4/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Gastrointestinal disorders
Constipation
|
5.4%
2/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Gastrointestinal disorders
Lip swelling
|
5.4%
2/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.1%
3/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.1%
3/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Nervous system disorders
Headache
|
13.5%
5/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.8%
4/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Metabolism and nutrition disorders
Anorexia
|
8.1%
3/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
|
Cardiac disorders
Palpitations
|
5.4%
2/37 • From the date of signing of the Informed Consent Form onwards until 30-35 days after last TMC435 intake.
5% cutoff is restricted to Total group. Adverse events reported for the total group rather than by genotype because enrollment numbers by genotype were small.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60