Trial Outcomes & Findings for Safety and Efficacy of Telaprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Subjects Co-Infected With Hepatitis C Virus (HCV) and HIV (NCT NCT00983853)
NCT ID: NCT00983853
Last Updated: 2013-10-10
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
62 participants
Primary outcome timeframe
12 weeks after first dose of study drug
Results posted on
2013-10-10
Participant Flow
Participant milestones
| Measure |
Part A: T/PR
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part A: Pbo/PR
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: EFV-based HAART + T/PR
Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: EFV-based HAART + Pbo/PR
Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: ATV/R-based HAART + T/PR
Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: ATV/R-based HAART + Pbo/PR
Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
17
|
8
|
15
|
8
|
|
Overall Study
COMPLETED
|
6
|
5
|
14
|
6
|
12
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
3
|
2
|
3
|
1
|
Reasons for withdrawal
| Measure |
Part A: T/PR
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part A: Pbo/PR
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: EFV-based HAART + T/PR
Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: EFV-based HAART + Pbo/PR
Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: ATV/R-based HAART + T/PR
Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine
Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
Part B: ATV/R-based HAART + Pbo/PR
Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine
Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks
Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks
Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks
Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing \<75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks
The dose of ribavirin used (fixed versus weight-based) was region dependent.
|
|---|---|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
2
|
2
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Overall Study
Unable to come to study follow-up visits
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Safety and Efficacy of Telaprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Subjects Co-Infected With Hepatitis C Virus (HCV) and HIV
Baseline characteristics by cohort
| Measure |
Part A: T/PR
n=7 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=6 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
n=16 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
n=15 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age Continuous
median (min, max)
|
39.4 years
n=5 Participants
|
47.5 years
n=7 Participants
|
47.5 years
n=5 Participants
|
47.0 years
n=4 Participants
|
52.0 years
n=21 Participants
|
39.0 years
n=8 Participants
|
44.5 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
53 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
17 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
42 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
12 participants
n=5 Participants
|
5 participants
n=4 Participants
|
13 participants
n=21 Participants
|
7 participants
n=8 Participants
|
42 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
2 participants
n=21 Participants
|
1 participants
n=8 Participants
|
16 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaska Native
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
1 participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
1 participants
n=8 Participants
|
|
Region of Enrollment
North America
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
8 participants
n=4 Participants
|
9 participants
n=21 Participants
|
4 participants
n=8 Participants
|
46 participants
n=8 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
8 participants
n=4 Participants
|
9 participants
n=21 Participants
|
4 participants
n=8 Participants
|
46 participants
n=8 Participants
|
|
Region of Enrollment
Europe
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
0 participants
n=4 Participants
|
6 participants
n=21 Participants
|
4 participants
n=8 Participants
|
14 participants
n=8 Participants
|
|
Region of Enrollment
Germany
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
1 participants
n=8 Participants
|
3 participants
n=8 Participants
|
|
Region of Enrollment
Spain
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
3 participants
n=8 Participants
|
9 participants
n=8 Participants
|
|
Region of Enrollment
France
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
0 participants
n=8 Participants
|
2 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after first dose of study drugPopulation: Subjects who were randomized and received at least 1 dose of study drug
Outcome measures
| Measure |
Part A: T/PR
n=7 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=6 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
n=16 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
n=15 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Proportion of Subjects Achieving Undetectable HCV RNA at Week 12
|
6 participants
|
2 participants
|
14 participants
|
2 participants
|
10 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 4 and 12 weeks after the first dose of study drugPopulation: Subjects who were randomized and received at least 1 dose of study drug
number of subjects with undetectable HCV RNA
Outcome measures
| Measure |
Part A: T/PR
n=7 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=6 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
n=16 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
n=15 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12
Week 4 (RVR)
|
5 participants
|
0 participants
|
12 participants
|
0 participants
|
9 participants
|
0 participants
|
|
Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12
Weeks 4 and 12 (eRVR)
|
4 participants
|
0 participants
|
12 participants
|
0 participants
|
7 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 12 weeks after last dose of study drugPopulation: subjects who received at least 1 dose of study drug.
Outcome measures
| Measure |
Part A: T/PR
n=7 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=6 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
n=16 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
n=15 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment
SVR12
|
5 participants
|
2 participants
|
11 participants
|
4 participants
|
12 participants
|
4 participants
|
|
Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment
SVR24
|
5 participants
|
2 participants
|
11 participants
|
4 participants
|
12 participants
|
4 participants
|
SECONDARY outcome
Timeframe: through 12 weeks after first dose of study drugPopulation: subjects with available plasma concentration data
Outcome measures
| Measure |
Part A: T/PR
n=15 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=13 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure
Cmin
|
0.8842 ratio (test/reference)
Interval 0.5467 to 1.43
|
1.3059 ratio (test/reference)
Interval 0.7981 to 2.1367
|
—
|
—
|
—
|
—
|
|
Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure
Cavg
|
0.9610 ratio (test/reference)
Interval 0.6615 to 1.3961
|
1.0930 ratio (test/reference)
Interval 0.7456 to 1.6023
|
—
|
—
|
—
|
—
|
|
Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure
Cmax
|
1.0061 ratio (test/reference)
Interval 0.7306 to 1.3855
|
1.0075 ratio (test/reference)
Interval 0.726 to 1.3982
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: through 12 weeks after first dose of study drugPopulation: subjects with available concentration data
Ctrough ratio of HAART medication with telaprevir (test) and without telaprevir (reference)
Outcome measures
| Measure |
Part A: T/PR
n=14 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=8 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART)
Efavirenz
|
0.94 ratio (test/reference)
Interval 0.42 to 2.84
|
0.79 ratio (test/reference)
Interval 0.48 to 1.48
|
—
|
—
|
—
|
—
|
|
Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART)
Tenofovir
|
1.06 ratio (test/reference)
Interval 0.46 to 17.4
|
0.64 ratio (test/reference)
Interval 0.3 to 2.01
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: through 12 weeks after first dose of study drugPopulation: subjects with available concentration data
Ctrough of HAART medication with telaprevir (test) and without telaprevir (reference)
Outcome measures
| Measure |
Part A: T/PR
n=13 Participants
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part A: Pbo/PR
n=7 Participants
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
|
Part B: EFV-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: EFV-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz (EFV)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + T/PR
Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
Part B: ATV/R-based HAART + Pbo/PR
Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir (ATV/r)-based highly active antiretroviral therapy (HAART) for the entire 48 week study.
|
|---|---|---|---|---|---|---|
|
Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART)
Atazanavir (N=12 T/PR, N=6 Pbo/PR)
|
1.16 ratio (test/reference)
Interval 0.39 to 45.0
|
1.03 ratio (test/reference)
Interval 0.49 to 2.05
|
—
|
—
|
—
|
—
|
|
Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART)
Tenofovir (N=13 T/PR, N=7 Pbo/PR)
|
0.75 ratio (test/reference)
Interval 0.28 to 40.7
|
0.93 ratio (test/reference)
Interval 0.55 to 1.68
|
—
|
—
|
—
|
—
|
|
Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART)
Ritonavir (N=9 T/PR, N=7 Pbo/PR)
|
0.72 ratio (test/reference)
Interval 0.08 to 4.4
|
0.74 ratio (test/reference)
Interval 0.21 to 4.2
|
—
|
—
|
—
|
—
|
Adverse Events
T/PR
Serious events: 7 serious events
Other events: 38 other events
Deaths: 0 deaths
Total PR
Serious events: 2 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
T/PR
n=38 participants at risk
Pooled T/PR from Part A and Part B
|
Total PR
n=22 participants at risk
Pooled PR from Part A and Part B
|
|---|---|---|
|
Infections and infestations
Groin Infection
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Appendicitis
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Pyelonephritis Acute
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Cellulitis Staphylococcal
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Staphylococcal Abscess
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Staphylococcal Infection
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Blood and lymphatic system disorders
Hemolytic Anemia
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Cardiac disorders
Acute Myocardial Infarction
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Non-cardiac Chest Pain
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Reproductive system and breast disorders
Epididymitis
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
Other adverse events
| Measure |
T/PR
n=38 participants at risk
Pooled T/PR from Part A and Part B
|
Total PR
n=22 participants at risk
Pooled PR from Part A and Part B
|
|---|---|---|
|
General disorders
Chills
|
15.8%
6/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
18.2%
4/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Pyrexia
|
21.1%
8/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Influenza-like Illness
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Irritability
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Fatigue
|
42.1%
16/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
40.9%
9/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Injection Site Erythema
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Pain
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
General disorders
Malaise
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
34.2%
13/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
22.7%
5/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Diarrhoea
|
23.7%
9/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
18.2%
4/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Vomiting
|
18.4%
7/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Anogenital Dysplasia
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Eye disorders
Cheilitis
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Dry Mouth
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Nervous system disorders
Headache
|
36.8%
14/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
27.3%
6/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Nervous system disorders
Dizziness
|
21.1%
8/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
39.5%
15/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.5%
4/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Depression
|
21.1%
8/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Insomnia
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
22.7%
5/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Anxiety
|
7.9%
3/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Depressed Mood
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Affect Lability
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Psychiatric disorders
Libido Decreased
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Fungal Skin Infection
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Infections and infestations
Sinusitis
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Blood and lymphatic system disorders
Neutropenia
|
23.7%
9/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
22.7%
5/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Blood and lymphatic system disorders
Anaemia
|
15.8%
6/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.8%
6/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
22.7%
5/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
7.9%
3/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Investigations
Weight Decreased
|
13.2%
5/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
22.7%
5/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Investigations
Blood Bilirubin Increased
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
10.5%
4/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
18.2%
4/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Anorexia
|
10.5%
4/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
4.5%
1/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.9%
3/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
13.6%
3/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
2.6%
1/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
9.1%
2/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal Pain
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Hepatobiliary disorders
Cholelithiasis
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Hepatobiliary disorders
Jaundice
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
|
Endocrine disorders
Hypothyroidism
|
5.3%
2/38 • first dose of study drug until 4 weeks after the last dose of study drug
|
0.00%
0/22 • first dose of study drug until 4 weeks after the last dose of study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60