Trial Outcomes & Findings for An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Participants (NCT NCT01290679)
NCT ID: NCT01290679
Last Updated: 2014-06-13
Results Overview
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
COMPLETED
PHASE3
393 participants
Week 36 or Week 60
2014-06-13
Participant Flow
The study was conducted from 18 January 2011 to 5 February 2013. The study was conducted at 76 sites in 14 countries.
393 participants were randomly allocated to the 2 treatment arms. 391 participants received at least 1 dose of study medication and were included in the intent-to-treat analysis set.
Participant milestones
| Measure |
TMC435 150mg 12Wks PR24/48
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
STARTED
|
257
|
134
|
|
Overall Study
COMPLETED
|
241
|
113
|
|
Overall Study
NOT COMPLETED
|
16
|
21
|
Reasons for withdrawal
| Measure |
TMC435 150mg 12Wks PR24/48
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
8
|
10
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
|
Overall Study
Subject Entered Another Trial
|
0
|
5
|
Baseline Characteristics
An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Participants
Baseline characteristics by cohort
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
Total
n=391 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46 years
n=99 Participants
|
47 years
n=107 Participants
|
47 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
117 Participants
n=99 Participants
|
57 Participants
n=107 Participants
|
174 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
140 Participants
n=99 Participants
|
77 Participants
n=107 Participants
|
217 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Week 36 or Week 60Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
|
81.3 Percentage of participants
|
50.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
|
78.6 Percentage of participants
|
50.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 48 or Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
|
80.5 Percentage of participants
|
50.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 28 or Week 52Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
|
84.8 Percentage of participants
|
53.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows changes from baseline in log10 HCV RNA.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
-5.34 log10 IU/mL
Standard Error 0.053
|
-4.21 log10 IU/mL
Standard Error 0.129
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
-5.27 log10 IU/mL
Standard Error 0.062
|
-4.93 log10 IU/mL
Standard Error 0.114
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
-3.60 log10 IU/mL
Standard Error 0.045
|
-1.22 log10 IU/mL
Standard Error 0.075
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
-4.52 log10 IU/mL
Standard Error 0.043
|
-1.21 log10 IU/mL
Standard Error 0.094
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
-5.28 log10 IU/mL
Standard Error 0.046
|
-2.72 log10 IU/mL
Standard Error 0.138
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
-5.83 log10 IU/mL
Standard Error 0.074
|
-5.28 log10 IU/mL
Standard Error 0.084
|
SECONDARY outcome
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows actual values of log10 HCV RNA levels.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
1.852 log10 IU/mL
Standard Error 0.400
|
5.171 log10 IU/mL
Standard Error 0.129
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
1.093 log10 IU/mL
Standard Error 0.027
|
3.657 log10 IU/mL
Standard Error 0.162
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
1.027 log10 IU/mL
Standard Error 0.034
|
2.157 log10 IU/mL
Standard Error 0.141
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
1.094 log10 IU/mL
Standard Error 0.049
|
1.388 log10 IU/mL
Standard Error 0.106
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
2.777 log10 IU/mL
Standard Error 0.050
|
5.165 log10 IU/mL
Standard Error 0.107
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
1.015 log10 IU/mL
Standard Error 0.061
|
0.960 log10 IU/mL
Standard Error 0.005
|
SECONDARY outcome
Timeframe: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants with Hepatitis C Virus (HCV) ribonucleic acid (RNA) plasma levels below the limit of detection (ie, \<25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA \<100 IU/mL, the percentage of HCV-Infected participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:> or =2 log 10 change from baseline
|
99.6 Percentage of participants
|
80.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:> or =2 log 10 change from baseline
|
99.2 Percentage of participants
|
97.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:> or =2 log 10 change from baseline
|
98.8 Percentage of participants
|
93.6 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL undetectable
|
100.0 Percentage of participants
|
95.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:<25 IU/mL undetectable
|
100.0 Percentage of participants
|
95.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL undetectable
|
93.7 Percentage of participants
|
31.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL undetectable
|
96.3 Percentage of participants
|
65.5 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL detectable or undetectable
|
4.7 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL detectable or undetectable
|
37.0 Percentage of participants
|
2.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL undetectable
|
0.4 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL undetectable
|
31.7 Percentage of participants
|
3.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL detectable or undetectable
|
98.0 Percentage of participants
|
45.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL detectable or undetectable
|
98.0 Percentage of participants
|
73.5 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL undetectable
|
66.7 Percentage of participants
|
88.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL detectable or undetectable
|
97.1 Percentage of participants
|
79.1 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL detectable or undetectable
|
80.7 Percentage of participants
|
12.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL detectable or undetectable
|
100.0 Percentage of participants
|
98.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<100 IU/mL
|
15.3 Percentage of participants
|
1.5 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<100 IU/mL
|
65.7 Percentage of participants
|
6.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<100 IU/mL
|
98.8 Percentage of participants
|
50.4 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL detectable or undetectable
|
77.8 Percentage of participants
|
97.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:> or =2 log 10 change from baseline
|
88.9 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:<25 IU/mL detectable or undetectable
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<100 IU/mL
|
92.0 Percentage of participants
|
14.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:> or =2 log 10 change from baseline
|
99.6 Percentage of participants
|
39.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<100 IU/mL
|
98.8 Percentage of participants
|
77.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL undetectable
|
95.9 Percentage of participants
|
68.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<100 IU/mL
|
98.0 Percentage of participants
|
83.6 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<100 IU/mL
|
77.8 Percentage of participants
|
97.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<100 IU/mL
|
100.0 Percentage of participants
|
98.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL undetectable
|
6.3 Percentage of participants
|
1.5 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:<100 IU/mL
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:> or = 2 log 10 change from baseline
|
96.9 Percentage of participants
|
20.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:> or =2 log 10 change from baseline
|
99.6 Percentage of participants
|
24.1 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:> or =2 log 10 change from baseline
|
100.0 Percentage of participants
|
98.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:> or =2 log 10 change from baseline
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 4Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
|
79.2 Percentage of participants
|
12.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Early Virologic Response (EVR)
|
98.8 Percentage of participants
|
89.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
|
96.8 Percentage of participants
|
44.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4 and 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
|
78.3 Percentage of participants
|
13.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 4Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group with \<1 log10 HCV RNA decrease at Week 4.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
|
0.4 Percentage of participants
|
17.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 4Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in each treatment group with HCV RNA levels \>1000 IU/mL at Week 4.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
|
1.2 Percentage of participants
|
61.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants with null response, defined as \<2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With Null Response
|
1.2 Percentage of participants
|
10.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants with partial response, defined as =\>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With Partial Response
|
0.4 Percentage of participants
|
17.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (\<25 IU/mL undetectable).
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With Viral Breakthrough
|
4.7 Percentage of participants
|
10.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (\<25 IU/mL undetectable) at the end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With Viral Relapse
|
12.3 Percentage of participants
|
23.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] levels \<25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
|
89.5 Percentage of participants
|
NA Percentage of participants
RGT criteria did not apply to PBO arm
|
SECONDARY outcome
Timeframe: Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Percentage of Participants With On-treatment Failure
|
7.0 Percentage of participants
|
32.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the median time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
|
14 Days
Interval 14.0 to 15.0
|
85 Days
Interval 57.0 to 112.0
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the median time in days to reach HCV RNA levels \<25 IU/mL undetectable.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
|
29 Days
Interval 28.0 to 29.0
|
113 Days
Interval 85.0 to 141.0
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the median time in days to reach HCV RNA levels \<100 IU/mL.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
|
8 Days
The 95% CI could not be calculated due to very low number of failures in the TMC435 group.
|
71 Days
Interval 57.0 to 86.0
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the median time in days to reach HCV RNA levels \<1000 IU/mL.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
|
4 Days
Interval 3.0 to 4.0
|
57 Days
Interval 56.0 to 58.0
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (\<25 IU/mL undetectable).
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
< 12 Weeks
|
1.2 Percentage of participants
|
3.7 Percentage of participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
Week 12 - Week 24
|
3.3 Percentage of participants
|
6.4 Percentage of participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
> Week 24
|
12.5 Percentage of participants
|
2.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (\<25 IU/mL undetectable) at the end of treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Time From End-of-treatment to Viral Relapse
|
229.77 Days
Standard Error 4.29
|
77.74 Days
Standard Error 2.34
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 164 of 257 participants in the TMC435 treatment group and 79 of 134 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=169 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=79 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
|
79.9 Percentage of participants
|
81.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 48Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the median time in weeks to normalization of ALT levels.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
|
2.14 Weeks
Interval 1.29 to 2.14
|
4.14 Weeks
Interval 4.14 to 12.0
|
SECONDARY outcome
Timeframe: At protocol-specified time points from the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=255 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
|
56611 ng*h/mL
Standard Deviation 66935.4
|
—
|
SECONDARY outcome
Timeframe: Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the mean (standard deviation) of C0h values of TMC435. NOTE: the timing of collection of blood samples post-dose for analysis at Week 2, 4, 8, and 12 was not specifed; only the interval was between blood samples was specified (ie, 2 samples collected 2 hours apart at Week 2, 4, 8, and 12).
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=255 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
|
1902 ng/mL
Standard Deviation 2781.1
|
—
|
SECONDARY outcome
Timeframe: At protocol-specified time points at Weeks 2, 4, 8, and 12Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
The table below shows the mean (standard deviation) of CL values of TMC435. NOTE: the pre-dose CL values taken at Weeks, 2, 4, 8, and 12 were averaged and then the mean values from all participants were averaged to provide the final value reported below.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=255 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Plasma Concentration of TMC435: Systemic Clearance (CL)
|
5.23 L/h
Standard Deviation 3.767
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 60 and Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
Study participants completed FSS questionnaires during study visits before treatment and throughout follow-up to rate the severity and impact of fatigue experienced in the preceding 2 weeks. FSS total scores are the average of nine questions with a range from 1 \[no fatigue\] to 7 \[worst fatigue\]; the possible score range from baseline to Week 60 would be 60-420 and to Week 72 would be 72-504. The average FSS total score from baseline to Week 60 and to Week 72 was calculated for each participant and then the average of those values were calculated to show the average FSS total score for each treatment group. The null hypothesis was that there would be no difference between the treatment arms in the FSS total score. The Table below shows the lease squares (LS) mean estimates of the area under the curve (AUC) at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=256 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Week 60
|
208.418 Scores on a scale*weeks
Interval 199.4881 to 217.3476
|
225.194 Scores on a scale*weeks
Interval 213.837 to 236.5513
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Week 72
|
240.695 Scores on a scale*weeks
Interval 230.1386 to 251.2542
|
259.532 Scores on a scale*weeks
Interval 246.081 to 272.9834
|
SECONDARY outcome
Timeframe: Baseline to Week 60 and Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). The average WPAI score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment groups in the AUC for the change from baseline to Week 72 (AUC72) in WPAI Productivity Scores. The Table below shows WPAI Productivity Scores at Week 72 (as well as at Week 60) from the model used to calculate the AUC and the statistical comparison between treatment groups.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=256 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
1781.768 Scores on a scale*weeks
Interval 1622.4802 to 1941.056
|
2106.131 Scores on a scale*weeks
Interval 1894.8814 to 2317.3811
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
1628.075 Scores on a scale*weeks
Interval 1492.3021 to 1763.8485
|
1910.235 Scores on a scale*weeks
Interval 1730.5026 to 2089.9681
|
SECONDARY outcome
Timeframe: Baseline to Week 60 and Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. The possible impairment in WPAI daily activity score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in daily activities. The average WPAI impairment in daily activity score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI impairment in daily activity score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment arms in the AUC for the change from baseline to Week 72 (AUC72) in WPAI impairment in daily activity scores. The Table below shows the WPAI Impairment in daily activity scores at Week 72 (as well as at Week 60) and the statistical analysis between treatment groups.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=256 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
1580.635 Scores on a scale*weeks
Interval 1445.8307 to 1715.4397
|
1863.071 Scores on a scale*weeks
Interval 1684.4355 to 2041.7065
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
1727.079 Scores on a scale*weeks
Interval 1568.9831 to 1885.1745
|
2056.283 Scores on a scale*weeks
Interval 1846.3791 to 2266.1868
|
SECONDARY outcome
Timeframe: Baseline to Week 60 and Week 72Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
Hours missed from work because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work). The possible WPAI WPAI absenteeism score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in WPAI absenteeism. The average WPAI absenteeism score from baseline to Week 60/72 was calculated for each participant and then the average of those values calculated for each treatment group. The area under the curve (AUC60/AUC72) over time from baseline to Week 60/72 was derived from a piecewise-linear model allowing the slopes to change at Week 4, 12, 24, 36, 48 and 60. The null hypothesis was there is no statistically significant difference between the treatment arms in the area under the curve (AUC) from baseline to Week 72 (AUC72) in WPAI absenteeism score.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=182 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=89 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
653.642 Scores on a scale*weeks
Interval 511.4925 to 795.7918
|
840.495 Scores on a scale*weeks
Interval 637.5293 to 1043.4599
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
698.223 Scores on a scale*weeks
Interval 533.6236 to 862.8224
|
886.425 Scores on a scale*weeks
Interval 650.2224 to 1122.6266
|
Adverse Events
TMC435 150mg 12Wks PR24/48
PBO 12Wks PR48
Serious adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 participants at risk
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 participants at risk
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Metabolism and nutrition disorders
Fluid overload
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Infections and infestations
Anal abscess
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Infections and infestations
Lymphadenitis bacterial
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Infections and infestations
Urinary tract infection
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Infections and infestations
Viral infection
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Nervous system disorders
Epilepsy
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Nervous system disorders
Memory impairment
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Nervous system disorders
Syncope
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Nervous system disorders
Thoracic outlet syndrome
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
0.78%
2/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Eye disorders
Hyphaema
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Eye disorders
Visual impairment
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Eye disorders
Retinal ischaemia
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Ear and labyrinth disorders
Mixed deafness
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Endocrine disorders
Hyperthyroidism
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Gastrointestinal disorders
Enterocutaneous fistula
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
General disorders
Death
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Psychiatric disorders
Aggression
|
0.39%
1/257 • 72 weeks
|
0.00%
0/134 • 72 weeks
|
|
Psychiatric disorders
Drug abuse
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/257 • 72 weeks
|
0.75%
1/134 • 72 weeks
|
Other adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=257 participants at risk
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12Wks PR48
n=134 participants at risk
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
General disorders
Fatigue
|
37.0%
95/257 • 72 weeks
|
41.8%
56/134 • 72 weeks
|
|
General disorders
Pyrexia
|
31.1%
80/257 • 72 weeks
|
39.6%
53/134 • 72 weeks
|
|
General disorders
Influenza like illness
|
25.7%
66/257 • 72 weeks
|
26.1%
35/134 • 72 weeks
|
|
General disorders
Asthenia
|
23.0%
59/257 • 72 weeks
|
28.4%
38/134 • 72 weeks
|
|
General disorders
Chills
|
8.2%
21/257 • 72 weeks
|
9.0%
12/134 • 72 weeks
|
|
General disorders
Injection site erythema
|
5.8%
15/257 • 72 weeks
|
6.7%
9/134 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.3%
65/257 • 72 weeks
|
25.4%
34/134 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
17.9%
46/257 • 72 weeks
|
11.2%
15/134 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
43/257 • 72 weeks
|
20.1%
27/134 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.9%
28/257 • 72 weeks
|
13.4%
18/134 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
1.6%
4/257 • 72 weeks
|
6.7%
9/134 • 72 weeks
|
|
Nervous system disorders
Headache
|
39.3%
101/257 • 72 weeks
|
36.6%
49/134 • 72 weeks
|
|
Nervous system disorders
Dizziness
|
8.2%
21/257 • 72 weeks
|
6.7%
9/134 • 72 weeks
|
|
Nervous system disorders
Disturbance in attention
|
5.1%
13/257 • 72 weeks
|
6.0%
8/134 • 72 weeks
|
|
Nervous system disorders
Dysgeusia
|
2.3%
6/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Gastrointestinal disorders
Nausea
|
24.5%
63/257 • 72 weeks
|
17.9%
24/134 • 72 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
13.2%
34/257 • 72 weeks
|
9.0%
12/134 • 72 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.6%
17/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
13/257 • 72 weeks
|
4.5%
6/134 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
4.7%
12/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.3%
11/257 • 72 weeks
|
9.0%
12/134 • 72 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.1%
8/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
22.6%
58/257 • 72 weeks
|
20.9%
28/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
32/257 • 72 weeks
|
10.4%
14/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.7%
25/257 • 72 weeks
|
9.7%
13/134 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.1%
8/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Psychiatric disorders
Insomnia
|
19.8%
51/257 • 72 weeks
|
15.7%
21/134 • 72 weeks
|
|
Psychiatric disorders
Depression
|
11.3%
29/257 • 72 weeks
|
14.2%
19/134 • 72 weeks
|
|
Psychiatric disorders
Mood altered
|
8.6%
22/257 • 72 weeks
|
11.2%
15/134 • 72 weeks
|
|
Psychiatric disorders
Anxiety
|
6.6%
17/257 • 72 weeks
|
4.5%
6/134 • 72 weeks
|
|
Psychiatric disorders
Sleep disorder
|
5.1%
13/257 • 72 weeks
|
3.7%
5/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
19.1%
49/257 • 72 weeks
|
21.6%
29/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
17.9%
46/257 • 72 weeks
|
24.6%
33/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.1%
13/257 • 72 weeks
|
6.7%
9/134 • 72 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.9%
10/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
32/257 • 72 weeks
|
16.4%
22/134 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.9%
23/257 • 72 weeks
|
8.2%
11/134 • 72 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.9%
46/257 • 72 weeks
|
15.7%
21/134 • 72 weeks
|
|
Investigations
Weight decreased
|
5.4%
14/257 • 72 weeks
|
4.5%
6/134 • 72 weeks
|
|
Investigations
Neutrophil count decreased
|
3.1%
8/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
|
Infections and infestations
Influenza
|
1.9%
5/257 • 72 weeks
|
6.0%
8/134 • 72 weeks
|
|
Infections and infestations
Sinusitis
|
1.9%
5/257 • 72 weeks
|
5.2%
7/134 • 72 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60