Trial Outcomes & Findings for An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients (NCT NCT01289782)
NCT ID: NCT01289782
Last Updated: 2014-06-04
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
395 participants
Week 36 or Week 60
2014-06-04
Participant Flow
The study was conducted from 18 January 2011 to 29 January 2013. The study was conducted at 71 sites in 13 countries.
395 participants were randomly allocated to the 2 treatment arms. 394 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
|
264
|
130
|
|
Overall Study
COMPLETED
|
239
|
118
|
|
Overall Study
NOT COMPLETED
|
25
|
12
|
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
|
14
|
7
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
2
|
|
Overall Study
Sponsor's Decision
|
1
|
0
|
|
Overall Study
Reason not specified
|
1
|
2
|
Baseline Characteristics
An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients
Baseline characteristics by cohort
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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=394 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48 years
n=5 Participants
|
48 years
n=7 Participants
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
116 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
172 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
148 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
222 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 |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
|
79.5 Percentage of participants
|
50 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
|
78.4 Percentage of participants
|
49.2 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
|
79.5 Percentage of participants
|
49.2 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
|
82.2 Percentage of participants
|
56.2 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 the change from baseline in log10 HCV RNA levels.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
-3.52 log10 IU/mL
Standard Error 0.0459
|
-0.93 log10 IU/mL
Standard Error 0.0774
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
-4.47 log10 IU/mL
Standard Error 0.0512
|
-1.08 log10 IU/mL
Standard Error 0.0835
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
-5.22 log10 IU/mL
Standard Error 0.0552
|
-2.56 log10 IU/mL
Standard Error 0.1434
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
-5.34 log10 IU/mL
Standard Error 0.0524
|
-4.18 log10 IU/mL
Standard Error 0.1510
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
-5.32 log10 IU/mL
Standard Error 0.0604
|
-4.89 log10 IU/mL
Standard Error 0.1289
|
|
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
-5.33 log10 IU/mL
Standard Error 0.2605
|
-5.23 log10 IU/mL
Standard Error 0.1670
|
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=264 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=130 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).
|
|---|---|---|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Day 3
|
2.914 log10 IU/mL
Standard Error 0.052
|
5.351 log10 IU/mL
Standard Error 0.104
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 1
|
1.973 log10 IU/mL
Standard Error 0.052
|
5.202 log10 IU/mL
Standard Error 0.114
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 4
|
1.223 log10 IU/mL
Standard Error 0.049
|
3.723 log10 IU/mL
Standard Error 0.159
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 12
|
1.090 log10 IU/mL
Standard Error 0.041
|
2.111 log10 IU/mL
Standard Error 0.155
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 24
|
1.113 log10 IU/mL
Standard Error 0.050
|
1.334 log10 IU/mL
Standard Error 0.110
|
|
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Week 48
|
0.993 log10 IU/mL
Standard Error 0.039
|
0.961 log10 IU/mL
Standard Error 0.006
|
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, \< 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 |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL undetectable
|
0.4 Percentage of participants
|
0.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL undetectable
|
6.6 Percentage of participants
|
0.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL undetectable
|
35.8 Percentage of participants
|
2.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL undetectable
|
90.0 Percentage of participants
|
26.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL undetectable
|
93.8 Percentage of participants
|
69.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL undetectable
|
93.4 Percentage of participants
|
78.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL undetectable
|
90.9 Percentage of participants
|
96.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL undetectable
|
90.9 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 undetectable
|
90.9 Percentage of participants
|
98.7 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<25 IU/mL undetectable/detectable
|
2.4 Percentage of participants
|
0.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<25 IU/mL undetectable/detectable
|
36.8 Percentage of participants
|
2.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<25 IU/mL undetectable/detectable
|
76.7 Percentage of participants
|
6.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<25 IU/mL undetectable/detectable
|
94.0 Percentage of participants
|
40.5 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<25 IU/mL undetectable/detectable
|
95.4 Percentage of participants
|
82.7 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<25 IU/mL undetectable/detectable
|
95.0 Percentage of participants
|
84.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<25 IU/mL undetectable/detectable
|
100.0 Percentage of participants
|
98.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 36:<25 IU/mL undetectable/detectable
|
100.0 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 undetectable/detectable
|
100.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Day 3:<100 IU/mL
|
11.4 Percentage of participants
|
1.6 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:<100 IU/mL
|
62.8 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:<100 IU/mL
|
85.2 Percentage of participants
|
7.8 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:<100 IU/mL
|
94.8 Percentage of participants
|
46.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 16:<100 IU/mL
|
96.7 Percentage of participants
|
84.6 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:<100 IU/mL
|
96.7 Percentage of participants
|
86.1 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 28:<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 36:<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
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 log10 change from baseline
|
95.3 Percentage of participants
|
13.3 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 1:> or = 2 log10 change from baseline
|
98.1 Percentage of participants
|
20.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 2:> or = 2 log10 change from baseline
|
98.8 Percentage of participants
|
35.2 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 8:> or = 2 log10 change from baseline
|
98.4 Percentage of participants
|
80.2 Percentage of participants
|
|
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
|
99.0 Percentage of participants
|
|
Percentage of Participants With On-treatment Virologic Response at All Time Points
Week 20:> or = 2 log10 change from baseline
|
98.3 Percentage of participants
|
97.0 Percentage of participants
|
|
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
|
97.5 Percentage of participants
|
|
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
|
98.7 Percentage of participants
|
|
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
|
98.7 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
|
79.5 Percentage of participants
|
11.8 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 greater than or equal to 2 log10 at Week 12.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Early Virologic Response (EVR)
|
99.2 Percentage of participants
|
85.2 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 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
|
92.8 Percentage of participants
|
50.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
|
78.9 Percentage of participants
|
11.7 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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
|
0 Percentage of participants
|
15.7 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=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
|
4.5 Percentage of participants
|
63.8 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 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=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With Null Response
|
0.8 Percentage of participants
|
14.8 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 with partial response, defined as greater than or equal to 2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With Partial Response
|
3.2 Percentage of participants
|
13.1 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 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=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With Viral Breakthrough
|
4.9 Percentage of participants
|
7.7 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 |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With Viral Relapse
|
9.0 Percentage of participants
|
22.6 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=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
|
83 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=264 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=130 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).
|
|---|---|---|
|
Percentage of Participants With On-treatment Failure
|
9.1 Percentage of participants
|
33.8 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 median time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
|
14 Days
95% Confidence Interval 1.25 • Interval 14.0 to 15.0
|
85 Days
95% Confidence Interval 4.89 • Interval 84.0 to 110.0
|
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 median time in days to reach HCV RNA levels \<25 IU/mL undetectable.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
|
28 Days
Majority of the participants had HCV RNA undetectable for the first time at Day 28. So they all are concentrated in that time point and there is no a range around Day 28 to be drawn.
|
111 Days
Interval 85.0 to 139.0
|
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 median time in days to reach HCV RNA levels \<100 IU/mL.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
|
28 Days
Majority of the participants had HCV RNA undetectable for the first time at Day 28. So they all are concentrated in that time point and there is no a range around Day 28 to be drawn.
|
84 Days
Interval 57.0 to 85.0
|
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 median time in days to reach HCV RNA levels \<1000 IU/mL.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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).
|
|---|---|---|
|
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
|
4 Days
Interval 3.0 to 4.0
|
56.5 Days
Interval 56.0 to 57.0
|
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=264 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=130 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).
|
|---|---|---|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
Week 12 - Week 24
|
2.5 Percentage of participants
|
6.8 Percentage of participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
> Week 24
|
0 Percentage of participants
|
1.2 Percentage of participants
|
|
The Percentage of Participants With Viral Breakthrough at Different Time Points
< 12 Weeks
|
2.7 Percentage of participants
|
1.5 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=264 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=130 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).
|
|---|---|---|
|
Time From End-of-treatment to Viral Relapse
|
100.96 Days
Standard Error 1.21
|
146.04 Days
Standard Error 5.22
|
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, 158 of 264 participants in the TMC435 treatment group and 89 of 130 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=158 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=89 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).
|
|---|---|---|
|
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
|
81.0 Percentage of participants
|
77.5 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 median time in weeks to normalization of ALT levels.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=158 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=89 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).
|
|---|---|---|
|
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
|
2.14 Weeks
Interval 1.86 to 4.0
|
8.14 Weeks
Interval 4.14 to 16.29
|
SECONDARY outcome
Timeframe: Fom 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 mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 for all participants. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then a median AUC value calcuated across all visits for each participant. The median AUC value across all visits for each participant was used to calculate the mean AUC 24 hr all participants in the study.
Outcome measures
| Measure |
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).
|
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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
|
54795 ng*h/mL
Standard Deviation 55627.3 • Interval 1.86 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Before administration of TMC435 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 for the C0h of TMC435.To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then a median C0H value calculated across visits for each participant. The median COh value for each participant across all visits was used to calculate the mean C0h for the study.
Outcome measures
| Measure |
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).
|
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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
|
1825 ng/mL
Standard Deviation 2306.1 • Interval 1.86 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Across 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 for the CL of TMC435.To calculate the mean CL for all participants in the study, CL values were first derived for each participant at each visit and then a median CL value calculated across visits for each participant. The median CL value for each participant was used to calculate the mean CL for all participants in the study.
Outcome measures
| Measure |
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).
|
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).
|
|---|---|---|
|
Plasma Concentration of TMC435: Systemic Clearance (CL)
|
5.05 L/h
Standard Deviation 3.319 • Interval 1.86 to 4.0
|
—
|
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 began and throughout treatment and follow-up to rate the severity and impact of fatigue they experienced in the preceding 2 weeks on their daily lives. FSS total scores are the average of nine questions with a range from 1 \[no fatigue\] to 7 \[worst possible fatigue\]. An area under the curve (AUC) analysis compared the overall severity of fatigue in each treatment group from baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the amount of fatigue participants experienced throughout the study resulting in equal AUC from baseline to Week 72 (AUC72) for FSS total scores. The Table below shows the lease squares (LS) mean estimates of 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=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=130 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).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Week 60
|
214.907 scores on a scale*weeks
Interval 205.9021 to 223.9115
|
235.586 scores on a scale*weeks
Interval 224.2016 to 246.97
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Week 72
|
250.522 scores on a scale*weeks
Interval 239.8398 to 261.2051
|
274.322 scores on a scale*weeks
Interval 260.8164 to 287.8279
|
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 during study visits throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). An area under the curve (AUC) analysis compared the overall WPAI Overall Work Productivity Scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the WPAI Overall Work Productivity Scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI Work Productivity Scores and the statistical comparison between treatment groups.
Outcome measures
| 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=130 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).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
1555.204 scores on a scale*weeks
Interval 1419.4052 to 1691.0026
|
1785.668 scores on a scale*weeks
Interval 1603.434 to 1967.9027
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
1718.241 scores on a scale*weeks
Interval 1558.7326 to 1877.7493
|
1966.449 scores on a scale*weeks
Interval 1752.2268 to 2180.672
|
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. Scores ranged from 0 (no effect on activities) to 10 (completely prevented me from doing my daily activities). An area under the curve (AUC) analysis compared the impairment in daily activity scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in impairment in daily activity scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in the impairment in daily activity scores and the statistical comparison between treatment groups.
Outcome measures
| 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=130 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).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
1514.400 scores on a scale*weeks
Interval 1379.7183 to 1649.0812
|
1792.460 scores on a scale*weeks
Interval 1611.2749 to 1973.6441
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
1667.735 scores on a scale*weeks
Interval 1509.618 to 1825.8526
|
1975.457 scores on a scale*weeks
Interval 1762.6198 to 2188.2942
|
SECONDARY outcome
Timeframe: Baseline to Week 60 and Week 72Population: Analysis Population Description: 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.
Time missed from work in hours 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, question #2). The number of hours missed from work because of HCV was divided by the total number of hours supposed to work, and expressed as a percentage. An area under the curve (AUC) analysis compared the WPAI absenteeism scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms WPAI absenteeism scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI absenteeism scores and the statistical comparison between treatment groups.
Outcome measures
| Measure |
TMC435 150mg 12Wks PR24/48
n=167 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=80 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).
|
|---|---|---|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 60
|
447.170 scores on a scale*weeks
Interval 329.8666 to 564.4736
|
400.771 scores on a scale*weeks
Interval 235.0986 to 566.4429
|
|
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Week 72
|
487.449 scores on a scale*weeks
Interval 352.1468 to 622.7508
|
430.285 scores on a scale*weeks
Interval 239.3346 to 621.2359
|
Adverse Events
TMC435 150mg 12Wks PR24/48
PBO 12Wks PR48
Serious adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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
Abscess limb
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Infections and infestations
Cellulitis
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Infections and infestations
Pneumonia
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Nervous system disorders
Syncope
|
1.1%
3/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Nervous system disorders
Migraine
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Hepatobiliary disorders
Hepatic lesion
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Injury, poisoning and procedural complications
Overdose
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Psychiatric disorders
Depression
|
0.76%
2/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Psychiatric disorders
Major depression
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Cardiac disorders
Palpitations
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Vascular disorders
Hypotension
|
0.38%
1/264 • 72 weeks
|
0.00%
0/130 • 72 weeks
|
|
Vascular disorders
Aortic stenosis
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Vascular disorders
Arterial stenosis limb
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Endocrine disorders
Goitre
|
0.00%
0/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
Other adverse events
| Measure |
TMC435 150mg 12Wks PR24/48
n=264 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=130 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
|
42.0%
111/264 • 72 weeks
|
40.8%
53/130 • 72 weeks
|
|
General disorders
Influenza like illness
|
23.5%
62/264 • 72 weeks
|
20.0%
26/130 • 72 weeks
|
|
General disorders
Pyrexia
|
19.3%
51/264 • 72 weeks
|
21.5%
28/130 • 72 weeks
|
|
General disorders
Chills
|
12.5%
33/264 • 72 weeks
|
13.8%
18/130 • 72 weeks
|
|
General disorders
Asthenia
|
9.5%
25/264 • 72 weeks
|
16.2%
21/130 • 72 weeks
|
|
General disorders
Pain
|
4.5%
12/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.8%
68/264 • 72 weeks
|
15.4%
20/130 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.7%
60/264 • 72 weeks
|
23.1%
30/130 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.5%
33/264 • 72 weeks
|
8.5%
11/130 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
11.4%
30/264 • 72 weeks
|
12.3%
16/130 • 72 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.7%
15/264 • 72 weeks
|
2.3%
3/130 • 72 weeks
|
|
Gastrointestinal disorders
Nausea
|
24.6%
65/264 • 72 weeks
|
24.6%
32/130 • 72 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
35/264 • 72 weeks
|
14.6%
19/130 • 72 weeks
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
23/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.4%
17/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Gastrointestinal disorders
Constipation
|
6.1%
16/264 • 72 weeks
|
3.1%
4/130 • 72 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
5.3%
14/264 • 72 weeks
|
3.8%
5/130 • 72 weeks
|
|
Nervous system disorders
Headache
|
33.3%
88/264 • 72 weeks
|
39.2%
51/130 • 72 weeks
|
|
Nervous system disorders
Dizziness
|
8.7%
23/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Nervous system disorders
Dysgeusia
|
6.1%
16/264 • 72 weeks
|
3.1%
4/130 • 72 weeks
|
|
Psychiatric disorders
Insomnia
|
21.2%
56/264 • 72 weeks
|
23.8%
31/130 • 72 weeks
|
|
Psychiatric disorders
Mood altered
|
14.8%
39/264 • 72 weeks
|
14.6%
19/130 • 72 weeks
|
|
Psychiatric disorders
Depression
|
8.7%
23/264 • 72 weeks
|
12.3%
16/130 • 72 weeks
|
|
Psychiatric disorders
Anxiety
|
6.1%
16/264 • 72 weeks
|
7.7%
10/130 • 72 weeks
|
|
Psychiatric disorders
Depressed mood
|
4.9%
13/264 • 72 weeks
|
8.5%
11/130 • 72 weeks
|
|
Psychiatric disorders
Sleep disorder
|
3.8%
10/264 • 72 weeks
|
5.4%
7/130 • 72 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
20.5%
54/264 • 72 weeks
|
11.5%
15/130 • 72 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
16.7%
44/264 • 72 weeks
|
18.5%
24/130 • 72 weeks
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.8%
18/264 • 72 weeks
|
3.8%
5/130 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.8%
39/264 • 72 weeks
|
13.8%
18/130 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.9%
34/264 • 72 weeks
|
16.2%
21/130 • 72 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.0%
21/264 • 72 weeks
|
7.7%
10/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.5%
25/264 • 72 weeks
|
15.4%
20/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.7%
23/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.4%
17/264 • 72 weeks
|
0.77%
1/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.1%
16/264 • 72 weeks
|
3.8%
5/130 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.76%
2/264 • 72 weeks
|
5.4%
7/130 • 72 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.8%
47/264 • 72 weeks
|
14.6%
19/130 • 72 weeks
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.3%
14/264 • 72 weeks
|
3.1%
4/130 • 72 weeks
|
|
Investigations
Neutrophil count decreased
|
3.8%
10/264 • 72 weeks
|
6.2%
8/130 • 72 weeks
|
|
Investigations
Alanine aminotransferase increased
|
1.1%
3/264 • 72 weeks
|
6.9%
9/130 • 72 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
1.1%
3/264 • 72 weeks
|
5.4%
7/130 • 72 weeks
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.38%
1/264 • 72 weeks
|
5.4%
7/130 • 72 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
3.0%
8/264 • 72 weeks
|
5.4%
7/130 • 72 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60