Trial Outcomes & Findings for An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy (NCT NCT01281839)
NCT ID: NCT01281839
Last Updated: 2014-04-23
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
394 participants
Week 36 or Week 60
2014-04-23
Participant Flow
The study was conducted from 18 January 2011 to 4 February 2013. The study was conducted at 81 sites in 14 countries.
394 participants were randomly allocated to the 2 treatment arms. 393 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 (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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 (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
STARTED
|
260
|
133
|
|
Overall Study
COMPLETED
|
250
|
119
|
|
Overall Study
NOT COMPLETED
|
10
|
14
|
Reasons for withdrawal
| Measure |
TMC435 150mg 12Wks PR24/48
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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 (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
6
|
3
|
|
Overall Study
Withdrawal by Subject
|
4
|
10
|
|
Overall Study
Reason not specified
|
0
|
1
|
Baseline Characteristics
An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy
Baseline characteristics by cohort
| Measure |
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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 (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
Total
n=393 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
52 years
n=7 Participants
|
52 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
81 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
135 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
179 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
258 Participants
n=5 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
|
36.1 Percentage of participants
|
79.2 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
|
33.8 Percentage of Participants
|
76.5 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
|
33.8 Percentage of Participants
|
77.3 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
|
48.1 Percentage of Participants
|
88.5 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 change from baseline in log10 HCV RNA levels.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
-1.039 log10 IU/mL
Standard Error 0.072
|
-3.537 log10 IU/mL
Standard Error 0.042
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
-1.099 log10 IU/mL
Standard Error 0.073
|
-4.535 log10 IU/mL
Standard Error 0.040
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
-2.638 log10 IU/mL
Standard Error 0.125
|
-5.295 log10 IU/mL
Standard Error 0.049
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
-4.476 log10 IU/mL
Standard Error 0.113
|
-5.404 log10 IU/mL
Standard Error 0.049
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
-5.373 log10 IU/mL
Standard Error 0.070
|
-5.449 log10 IU/mL
Standard Error 0.036
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
-5.473 log10 IU/mL
Standard Error 0.068
|
-5.635 log10 IU/mL
Standard Error 0.212
|
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. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
5.445 log10 IU/mL
Standard Error 0.084
|
2.884 log10 IU/mL
Standard Error 0.049
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
5.376 log10 IU/mL
Standard Error 0.084
|
1.889 log10 IU/mL
Standard Error 0.041
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
3.838 log10 IU/mL
Standard Error 0.130
|
1.128 log10 IU/mL
Standard Error 0.034
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
2.005 log10 IU/mL
Standard Error 0.109
|
1.018 log10 IU/mL
Standard Error 0.034
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
1.108 log10 IU/mL
Standard Error 0.042
|
0.956 log10 IU/mL
Standard Error 0.002
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
0.995 log10 IU/mL
Standard Error 0.013
|
0.954 log10 IU/mL
Standard Error 0.000
|
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 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 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:> or = 2 log10 change from baseline
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:> or = 2 log10 change from baseline
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:> or = 2 log10 change from baseline
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:> or = 2 log10 change from baseline
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL undetectable
|
0.8 Percentage of Participants
|
0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL undetectable
|
0 Percentage of Participants
|
3.9 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL undetectable
|
0.8 Percentage of Participants
|
28.3 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL undetectable
|
15.0 Percentage of Participants
|
95.7 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL
|
47.4 Percentage of Participants
|
98.4 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL
|
65.5 Percentage of Participants
|
99.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL
|
84.5 Percentage of Participants
|
88.9 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL
|
91.9 Percentage of Participants
|
90.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:<25 IU/mL
|
91.7 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL undetectable/detectable
|
0.8 Percentage of Participants
|
3.1 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL undetectable/detectable
|
0.8 Percentage of Participants
|
35.9 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL undetectable/detectable
|
1.5 Percentage of Participants
|
82.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL undetectable/detectable
|
27.6 Percentage of Participants
|
98.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL undetectable/detectable
|
77.6 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL undetectable/detectable
|
89.4 Percentage of Participants
|
99.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL undetectable/detectable
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL undetectable/detectable
|
99.0 Percentage of Participants
|
90.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 42:<25 IU/mL undetectable/detectable
|
97.9 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<100 IU/mL
|
0.8 Percentage of Participants
|
9.1 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<100 IU/mL
|
0.8 Percentage of Participants
|
62.2 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<100 IU/mL
|
2.3 Percentage of Participants
|
92.2 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<100 IU/mL
|
37.0 Percentage of Participants
|
98.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<100 IU/mL
|
84.5 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<100 IU/mL
|
93.8 Percentage of Participants
|
99.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<100 IU/mL
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<100 IU/mL
|
100.0 Percentage of Participants
|
90.0 Percentage of Participants
|
|
The 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
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:> or = 2 log10 change from baseline
|
14.1 Percentage of Participants
|
97.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:> or = 2 log10 change from baseline
|
13.7 Percentage of Participants
|
99.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:> or = 2 log10 change from baseline
|
35.4 Percentage of Participants
|
99.6 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:> or = 2 log10 change from baseline
|
87.4 Percentage of Participants
|
98.4 Percentage of Participants
|
|
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:> or = 2 log10 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
|
3.1 Percentage of Participants
|
77.2 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 who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Early Virologic Response (EVR)
|
95.2 Percentage of Participants
|
98.8 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
|
27.4 Percentage of Participants
|
98.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 4 and 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 eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
|
1.6 Percentage of Participants
|
77.6 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
|
9.3 Percentage of Participants
|
0.8 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
|
69.9 Percentage of Participants
|
1.9 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Null Response
|
4.8 Percentage of Participants
|
1.2 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Partial Response
|
0 Percentage of Participants
|
10.5 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Viral Breakthrough
|
2.3 Percentage of Participants
|
0.0 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 (less than 25 IU/mL undetectable) at the end of treatment.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Viral Relapse
|
50.5 Percentage of Participants
|
18.9 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
|
0 Percentage of Participants
|
90.0 Percentage of Participants
|
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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With On-treatment Failure
|
27.1 Percentage of Participants
|
3.1 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 mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
|
141 Days
Interval 113.0 to 167.0
|
28 Days
Interval 28.0 to 29.0
|
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 mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
|
110 Days
Interval 85.0 to 113.0
|
14 Days
Interval 14.0 to 15.0
|
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 mean time in days to reach HCV RNA levels \<100 IU/mL.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
|
85 Days
Interval 83.0 to 85.0
|
8 Days
95% CI were not calculated because the number of censored values was very low (\<5%) and the response occurred very rapidly in the responders (85% of the subjects had HCV RNA\<100 IU/mL at Week 2).
|
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 mean time in days to reach HCV RNA levels \<1000 IU/mL.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
|
57 Days
Interval 57.0 to 58.0
|
4 Days
Interval 3.0 to 4.0
|
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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
=<12 weeks
|
0.0 Percentage of Participants
|
1.9 Percentage of Participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
>12-=<24 weeks
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
>24 weeks
|
0.0 Percentage of Participants
|
10.0 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 |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Time From End-of-treatment to Viral Relapse
|
115.22 Days
Standard Error 6.72
|
284.09 Days
Standard Error 6.56
|
SECONDARY outcome
Timeframe: Up to Week 48Population: Participants with baseline ALT values out of normal range were used for this analysis from intent-to treat population (defined as all participants who were randomized and received at least one dose of study medication).
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 156 of 260 participants in the TMC435 treatment group and 84 of 133 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 |
PBO 12Wks PR48
n=84 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=156 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
|
69.0 Percentage of Participants
|
69.9 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 to normalization of ALT levels.
Outcome measures
| Measure |
PBO 12Wks PR48
n=133 Participants
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=260 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
|
8.00 Weeks
Interval 4.14 to 15.86
|
7.86 Weeks
Interval 2.14 to 16.14
|
SECONDARY outcome
Timeframe: From the time of administration up to 24 hours after dosing through 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 mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study.
Outcome measures
| Measure |
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=259 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
|
—
|
60987 ng*h/mL
Standard Deviation 67577.4 • Interval 2.14 to 16.14
|
SECONDARY outcome
Timeframe: Before administration of TMC435 through 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 mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study.
Outcome measures
| Measure |
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=259 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
|
—
|
2081 ng/mL
Standard Deviation 2807.6 • Interval 2.14 to 16.14
|
SECONDARY outcome
Timeframe: From the time of administration through 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 mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study.
Outcome measures
| Measure |
PBO 12Wks PR48
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
TMC435 150mg 12Wks PR24/48
n=259 Participants
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Systemic Clearance (CL)
|
—
|
4.92 L/h
Standard Deviation 3.438 • Interval 2.14 to 16.14
|
Adverse Events
TMC435 150mg 12Wks PR24/48
PBO 12Wks PR48
Serious adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=260 participants at risk
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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 at risk
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.77%
2/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Infections and infestations
Appendicitis
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Infections and infestations
Endocarditis
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Infections and infestations
Septic shock
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Infections and infestations
Bacterial prostatitis
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Infections and infestations
Bronchitis
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Infections and infestations
Infection
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Cardiac disorders
Angina pectoris
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Cardiac disorders
Bradycardia
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Cardiac disorders
Myocardial ischaemia
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia haemolytic autoimmune
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Hepatobiliary disorders
Hepatitis
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Nervous system disorders
Guillain-Barre syndrome
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Nervous system disorders
Presyncope
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Psychiatric disorders
Confusional state
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Psychiatric disorders
Depression
|
0.38%
1/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.77%
2/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
General disorders
Pyrexia
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.38%
1/260 • 72 weeks
|
0.00%
0/133 • 72 weeks
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/260 • 72 weeks
|
0.75%
1/133 • 72 weeks
|
Other adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=260 participants at risk
Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (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 at risk
Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
General disorders
Fatigue
|
33.5%
87/260 • 72 weeks
|
43.6%
58/133 • 72 weeks
|
|
General disorders
Influenza like illness
|
30.0%
78/260 • 72 weeks
|
20.3%
27/133 • 72 weeks
|
|
General disorders
Pyrexia
|
24.2%
63/260 • 72 weeks
|
22.6%
30/133 • 72 weeks
|
|
General disorders
Asthenia
|
21.9%
57/260 • 72 weeks
|
18.8%
25/133 • 72 weeks
|
|
General disorders
Injection site erythema
|
8.1%
21/260 • 72 weeks
|
6.8%
9/133 • 72 weeks
|
|
General disorders
Chills
|
6.5%
17/260 • 72 weeks
|
8.3%
11/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
27.7%
72/260 • 72 weeks
|
27.8%
37/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.7%
33/260 • 72 weeks
|
14.3%
19/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.0%
26/260 • 72 weeks
|
12.8%
17/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.2%
24/260 • 72 weeks
|
13.5%
18/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.4%
14/260 • 72 weeks
|
3.0%
4/133 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema
|
2.7%
7/260 • 72 weeks
|
5.3%
7/133 • 72 weeks
|
|
Nervous system disorders
Headache
|
33.5%
87/260 • 72 weeks
|
36.1%
48/133 • 72 weeks
|
|
Nervous system disorders
Dizziness
|
5.4%
14/260 • 72 weeks
|
4.5%
6/133 • 72 weeks
|
|
Nervous system disorders
Dysgeusia
|
4.6%
12/260 • 72 weeks
|
5.3%
7/133 • 72 weeks
|
|
Nervous system disorders
Disturbance in attention
|
3.8%
10/260 • 72 weeks
|
5.3%
7/133 • 72 weeks
|
|
Gastrointestinal disorders
Nausea
|
22.7%
59/260 • 72 weeks
|
19.5%
26/133 • 72 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
13.8%
36/260 • 72 weeks
|
16.5%
22/133 • 72 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.9%
18/260 • 72 weeks
|
6.8%
9/133 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
10/260 • 72 weeks
|
6.8%
9/133 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
3.5%
9/260 • 72 weeks
|
6.0%
8/133 • 72 weeks
|
|
Psychiatric disorders
Insomnia
|
18.8%
49/260 • 72 weeks
|
24.8%
33/133 • 72 weeks
|
|
Psychiatric disorders
Mood altered
|
9.6%
25/260 • 72 weeks
|
16.5%
22/133 • 72 weeks
|
|
Psychiatric disorders
Depression
|
8.5%
22/260 • 72 weeks
|
7.5%
10/133 • 72 weeks
|
|
Psychiatric disorders
Sleep disorder
|
5.8%
15/260 • 72 weeks
|
10.5%
14/133 • 72 weeks
|
|
Psychiatric disorders
Depressed mood
|
3.8%
10/260 • 72 weeks
|
6.0%
8/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.1%
34/260 • 72 weeks
|
15.8%
21/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
26/260 • 72 weeks
|
3.8%
5/133 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.2%
16/260 • 72 weeks
|
6.0%
8/133 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.0%
39/260 • 72 weeks
|
12.8%
17/133 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
26/260 • 72 weeks
|
9.0%
12/133 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.8%
15/260 • 72 weeks
|
6.0%
8/133 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
15.4%
40/260 • 72 weeks
|
18.0%
24/133 • 72 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
14.2%
37/260 • 72 weeks
|
19.5%
26/133 • 72 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.5%
35/260 • 72 weeks
|
18.0%
24/133 • 72 weeks
|
|
Infections and infestations
Nasopharyngitis
|
1.9%
5/260 • 72 weeks
|
5.3%
7/133 • 72 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60