Hepatitis C
Conditions
Brief summary
The purpose of this study is to treat human immunodeficiency virus (HIV) and Hepatitis C Virus (HCV) co-infected subjects with telaprevir, pegylated interferon alfa-2a (Peg-IFN-alfa-2a), and ribavirin (RBV) to achieve undetectable hepatitis C virus ribonucleic acid (HCV RNA) 12 weeks after the last planned dose of study drug.
Interventions
DRUGTelaprevir
Tablet
DRUGRibavirin
Tablet
BIOLOGICALPegylated Interferon Alfa-2a
Subcutaneous Injection
Atazanavir/ritonavir (ATV/r) based HAART, Efavirenz (EFV) based HAART, or Raltegravir (RAL) based HAART, as per standard practice. HAART medications were not considered study drugs.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have chronic, genotype 1a or 1b, hepatitis C with HCV RNA greater than (\>) 1000 international units per milliliter (IU/mL) * Population A: HCV Pegylated interferon (Peg-IFN)/RBV treatment naive (received no prior HCV therapy)or Peg-IFN/RBV prior treatment with relapse * Population B: Peg-IFN/RBV prior null or partial responder * Participants must not have achieved undetectable HCV RNA 24 weeks after the last planned dose of study drug (SVR24) after at least 1 prior course of Peg IFN/RBV therapy of standard duration * Participant must have positive HIV antibody at Screening * Participant must have a diagnosis of HIV-1 infection \>6 months before Screening * Participants should be taking 1 of the following permissible highly active antiretroviral therapy (HAART) regimens for HIV continuously for 12 weeks prior to screening: * Atripla® or equivalent components (efavirenz, tenofovir, emtricitabine) * Efavirenz plus Epzicom® (abacavir, lamivudine) or equivalent components * Boosted atazanavir (atazanavir with ritonavir) plus Truvada® (tenofovir, emtricitabine) or equivalent components * Boosted atazanavir plus Epzicom®, or equivalent components * Raltegravir plus Truvada®, or equivalent components * Raltegravir plus Epzicom®, or equivalent components * Cluster of differentiation 4 (CD4) counts and human immunodeficiency virus Type 1 (HIV-1) ribonucleic acid (RNA) meeting acceptable criteria at Screening as specified in the protocol * Laboratory values within acceptable ranges at Screening as specified in the protocol
Exclusion criteria
* Subjects anticipating a need to switch HAART regimens within 14 weeks after Day 1 or any switches occurring 12 weeks prior to Day 1 * Use of azidothymidine (AZT), didanosine (ddI) or stavudine (d4T) nucleosides * Contraindications to any planned HAART component as per the respective drug labeling information * Contraindications to Peg-IFN or RBV * Evidence of hepatic decompensation * Clinical suspicion of acute hepatitis * Any other cause of liver disease in addition to hepatitis C * History of organ transplantation (except cornea and skin) * Autoimmune-mediated disease * Participated in any investigational drug study within 90 days before Day 1 * Previous treatment with an HCV protease inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | 12 weeks after last planned dose of study drug (up to Week 60) | SVR 12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 12 weeks after last planned dose of study drug. The plasma hepatitis C virus ribonucleic acid (HCV RNA) level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Rapid Viral Response (RVR) | Week 4 | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. RVR was defined as undetectable HCV RNA (\<lower limit of quantification) 4 weeks after the start of study treatment. |
| Percentage of Participants With Extended Rapid Viral Response (eRVR) | Week 4 and Week 12 | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. eRVR was defined as undetectable HCV RNA (\<lower limit of quantification) at both 4 weeks and 12 weeks after the start of study treatment. |
| Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) | EOT (up to Week 48) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Percentage of participants with undetectable HCV RNA (\<lower limit of quantification) at EOT (up to Week 48) are reported. Data for this outcome was not planned to be reported by prior response. |
| Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | 24 weeks after last planned dose of study drug (up to Week 72) | SVR 24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 24 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL). |
| Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Day -14 to Day -1 and Week 1 for ATV, EFV, and RAL; Week 1 for telaprevir | Cmax, Cmin, and Cavg were reported for atazanavir (ATV), efavirenz (EFV), raltegravir (RAL), and telaprevir. |
| Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Baseline, follow-up (Week 96) | Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA \>=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by HAART treatment. |
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 52 | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. |
Countries
Canada, Germany, Puerto Rico, Spain, United States
Participant flow
Recruitment details
Study included Treatment-Naïve (no prior hepatitis C virus \[HCV\] therapy); Prior Relapser (prior HCV treatment with pegylated interferon alfa/ribavirin \[Peg-IFN/RBV\] and experienced viral relapse); and Prior Null/Partial Responder (prior HCV treatment with Peg-IFN/RBV and had null/partial response) participants.
Pre-assignment details
Efficacy analyses were reported as per highly active antiretroviral therapy (HAART) treatment (reporting arms) and also separately as per prior response (in categories) (Treatment-Naive, Prior Relapser, Prior Null Responder, Prior Partial Responder as well as for Total Participants), unless otherwise specified.
Participants by arm
| Arm | Count |
|---|---|
| T/PR + HAART Regimen (ATV/r-Based) Participants who were receiving ATV/r based HAART at baseline, received Telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 800 mg/day for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | 54 |
| T/PR + HAART Regimen (EFV-Based) Participants who were receiving EFV based HAART at baseline, received Telaprevir 1125 mg tablet three times a day for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 800 mg/day for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | 69 |
| T/PR + HAART Regimen (RAL-Based) Participants who were receiving RAL based HAART at baseline, received Telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 800 mg/day for 24 or 48 weeks, depending on individual response to telaprevir treatment. Participants continued their HAART, as per standard practice and investigator discretion. | 59 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 5 | 3 |
| Overall Study | No Study Medication | 1 | 0 | 2 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 1 | 3 | 3 |
| Overall Study | Withdrawal of Consent | 3 | 7 | 7 |
Baseline characteristics
| Characteristic | T/PR + HAART Regimen (ATV/r-Based) | T/PR + HAART Regimen (EFV-Based) | T/PR + HAART Regimen (RAL-Based) | Total |
|---|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 8.81 | 49.6 years STANDARD_DEVIATION 8.84 | 48.4 years STANDARD_DEVIATION 9.58 | 49.5 years STANDARD_DEVIATION 9.06 |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 48 Participants | 60 Participants | 44 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 54 / 54 | 66 / 69 | 56 / 59 |
| serious Total, serious adverse events | 7 / 54 | 8 / 69 | 9 / 59 |
Outcome results
Primary
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
SVR 12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 12 weeks after last planned dose of study drug. The plasma hepatitis C virus ribonucleic acid (HCV RNA) level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL).
Time frame: 12 weeks after last planned dose of study drug (up to Week 60)
Population: Safety Set included all participants who received at least 1 dose of study drug. Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Partial Responder (n= 7, 8, 9) | 14.3 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Null Responder (n= 15, 11, 15) | 40 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Treatment Naïve (n= 24, 39, 31) | 66.7 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Relapser (n=8, 11, 4) | 75.0 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Total (n= 54, 69, 59) | 53.7 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Null Responder (n= 15, 11, 15) | 36.4 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Treatment Naïve (n= 24, 39, 31) | 59.0 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Relapser (n=8, 11, 4) | 54.5 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Partial Responder (n= 7, 8, 9) | 87.5 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Total (n= 54, 69, 59) | 58.0 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Total (n= 54, 69, 59) | 57.6 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Partial Responder (n= 7, 8, 9) | 55.6 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Treatment Naïve (n= 24, 39, 31) | 61.3 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Null Responder (n= 15, 11, 15) | 40 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | Prior Relapser (n=8, 11, 4) | 100 percentage of participants |
Secondary
Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg)
Cmax, Cmin, and Cavg were reported for atazanavir (ATV), efavirenz (EFV), raltegravir (RAL), and telaprevir.
Time frame: Day -14 to Day -1 and Week 1 for ATV, EFV, and RAL; Week 1 for telaprevir
Population: Full Analysis set.Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cavg(n=0, 0, 35) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmin(n=0, 60, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmax(n=49, 59, 54) | 3160 nanogram per milliliter (ng/mL) | Standard Deviation 1180 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmin(n=0, 0, 52) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cavg(n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmax (n=42, 0, 0) | 2820 nanogram per milliliter (ng/mL) | Standard Deviation 1570 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmax(n=46, 0, 0) | 2870 nanogram per milliliter (ng/mL) | Standard Deviation 1580 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmax (n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cavg(n=30, 32, 26) | 2320 nanogram per milliliter (ng/mL) | Standard Deviation 907 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmax(n=0, 0, 52) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmin (n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cavg (n=0, 0, 34) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cavg (n=0, 47, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmin (n=42, 0, 0) | 1280 nanogram per milliliter (ng/mL) | Standard Deviation 636 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmin(n=49, 59, 54) | 1650 nanogram per milliliter (ng/mL) | Standard Deviation 863 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmin (n=0, 0, 49) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cavg (n=30, 0, 0) | 1320 nanogram per milliliter (ng/mL) | Standard Deviation 685 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cavg(n=41, 0, 0) | 1100 nanogram per milliliter (ng/mL) | Standard Deviation 647 |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmax (n=0, 0, 49) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmax(n=0, 60, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (ATV/r-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmin(n=46, 0, 0) | 991 nanogram per milliliter (ng/mL) | Standard Deviation 635 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmax(n=0, 0, 52) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cavg(n=30, 32, 26) | 2430 nanogram per milliliter (ng/mL) | Standard Deviation 1290 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmax(n=46, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmin(n=46, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cavg(n=41, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmax (n=42, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmin (n=42, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cavg (n=30, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmax(n=0, 60, 0) | 3800 nanogram per milliliter (ng/mL) | Standard Deviation 2600 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmin(n=0, 60, 0) | 2560 nanogram per milliliter (ng/mL) | Standard Deviation 1900 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cavg(n=0, 51, 0) | 2150 nanogram per milliliter (ng/mL) | Standard Deviation 1680 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmax (n=0, 51, 0) | 3340 nanogram per milliliter (ng/mL) | Standard Deviation 2450 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmin (n=0, 51, 0) | 2290 nanogram per milliliter (ng/mL) | Standard Deviation 1880 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cavg (n=0, 47, 0) | 1920 nanogram per milliliter (ng/mL) | Standard Deviation 1400 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmin(n=0, 0, 52) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cavg(n=0, 0, 35) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmax (n=0, 0, 49) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmin (n=0, 0, 49) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cavg (n=0, 0, 34) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmax(n=49, 59, 54) | 3780 nanogram per milliliter (ng/mL) | Standard Deviation 1670 |
| T/PR + HAART Regimen (EFV-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmin(n=49, 59, 54) | 1750 nanogram per milliliter (ng/mL) | Standard Deviation 961 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmin(n=0, 0, 52) | 196 nanogram per milliliter (ng/mL) | Standard Deviation 198 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmax(n=0, 60, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmax(n=49, 59, 54) | 3470 nanogram per milliliter (ng/mL) | Standard Deviation 868 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cavg(n=0, 0, 35) | 483 nanogram per milliliter (ng/mL) | Standard Deviation 429 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cavg (n=30, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmin(n=46, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmax (n=0, 0, 49) | 2320 nanogram per milliliter (ng/mL) | Standard Deviation 1970 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmin (n=42, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cavg(n=30, 32, 26) | 2520 nanogram per milliliter (ng/mL) | Standard Deviation 643 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cmin (n=0, 0, 49) | 281 nanogram per milliliter (ng/mL) | Standard Deviation 435 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Week 1, Cmax (n=42, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | Telaprevir: Week 1, Cmin(n=49, 59, 54) | 1840 nanogram per milliliter (ng/mL) | Standard Deviation 741 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Week 1, Cavg (n=0, 0, 34) | 643 nanogram per milliliter (ng/mL) | Standard Deviation 539 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmin (n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cavg(n=41, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cavg (n=0, 47, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Week 1, Cmax (n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cavg(n=0, 51, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | RAL: Day -14 to Day -1, Cmax(n=0, 0, 52) | 1900 nanogram per milliliter (ng/mL) | Standard Deviation 1880 |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | EFV: Day -14 to Day -1, Cmin(n=0, 60, 0) | NA nanogram per milliliter (ng/mL) | — |
| T/PR + HAART Regimen (RAL-Based) | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) | ATV: Day -14 to Day -1, Cmax(n=46, 0, 0) | NA nanogram per milliliter (ng/mL) | — |
Secondary
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA \>=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by HAART treatment.
Time frame: Baseline, follow-up (Week 96)
Population: Full analysis set. Here number of participants analyzed = participants who were evaluable for this measure and n = participants evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Baseline (n = 180) | 2 participants |
| T/PR + HAART Regimen (ATV/r-Based) | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region | Follow-up (n = 26) | 11 participants |
Secondary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Time frame: Up to Week 52
Population: Safety set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 100 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 13.0 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 95.7 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 11.6 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 94.9 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 15.3 percentage of participants |
Secondary
Percentage of Participants With Extended Rapid Viral Response (eRVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. eRVR was defined as undetectable HCV RNA (\<lower limit of quantification) at both 4 weeks and 12 weeks after the start of study treatment.
Time frame: Week 4 and Week 12
Population: Safety set. Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Partial Responder (n= 7, 8, 9) | 14.3 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Null Responder (n= 15, 11, 15) | 26.7 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Treatment Naïve (n= 24, 39, 31) | 50.0 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Relapser (n=8, 11, 4) | 62.5 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Total (n= 54, 69, 59) | 40.7 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Null Responder (n= 15, 11, 15) | 54.5 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Treatment Naïve (n= 24, 39, 31) | 53.8 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Relapser (n=8, 11, 4) | 72.7 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Partial Responder (n= 7, 8, 9) | 50.0 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Total (n= 54, 69, 59) | 56.5 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Total (n= 54, 69, 59) | 59.3 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Partial Responder (n= 7, 8, 9) | 44.4 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Treatment Naïve (n= 24, 39, 31) | 61.3 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Null Responder (n= 15, 11, 15) | 53.3 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Extended Rapid Viral Response (eRVR) | Prior Relapser (n=8, 11, 4) | 100 percentage of participants |
Secondary
Percentage of Participants With Rapid Viral Response (RVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. RVR was defined as undetectable HCV RNA (\<lower limit of quantification) 4 weeks after the start of study treatment.
Time frame: Week 4
Population: Safety set. Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Partial Responder (n= 7, 8, 9) | 42.9 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Null Responder (n= 15, 11, 15) | 26.7 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Treatment Naïve (n= 24, 39, 31) | 50.0 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Relapser (n=8, 11, 4) | 62.5 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Total (n= 54, 69, 59) | 44.4 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Null Responder (n= 15, 11, 15) | 54.5 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Treatment Naïve (n= 24, 39, 31) | 53.8 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Relapser (n=8, 11, 4) | 72.7 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Partial Responder (n= 7, 8, 9) | 50.0 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Total (n= 54, 69, 59) | 56.5 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Total (n= 54, 69, 59) | 66.1 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Partial Responder (n= 7, 8, 9) | 44.4 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Treatment Naïve (n= 24, 39, 31) | 74.2 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Null Responder (n= 15, 11, 15) | 53.3 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Rapid Viral Response (RVR) | Prior Relapser (n=8, 11, 4) | 100 percentage of participants |
Secondary
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24)
SVR 24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 24 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL).
Time frame: 24 weeks after last planned dose of study drug (up to Week 72)
Population: Safety set. Here number of participants analyzed = participants evaluable for this measure and n = participants evaluable for specified categories, for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Partial Responder (n= 7, 8, 9) | 14.3 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Null Responder (n= 15, 9, 14) | 33.3 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Treatment Naïve (n= 23, 38, 29) | 65.2 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Relapser (n=8, 11, 4) | 75.0 percentage of participants |
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Total (n= 53, 66, 56) | 50.9 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Null Responder (n= 15, 9, 14) | 22.2 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Treatment Naïve (n= 23, 38, 29) | 57.9 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Relapser (n=8, 11, 4) | 54.5 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Partial Responder (n= 7, 8, 9) | 75.0 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Total (n= 53, 66, 56) | 54.5 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Total (n= 53, 66, 56) | 51.8 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Partial Responder (n= 7, 8, 9) | 55.6 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Treatment Naïve (n= 23, 38, 29) | 51.7 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Null Responder (n= 15, 9, 14) | 35.7 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) | Prior Relapser (n=8, 11, 4) | 100 percentage of participants |
Secondary
Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Percentage of participants with undetectable HCV RNA (\<lower limit of quantification) at EOT (up to Week 48) are reported. Data for this outcome was not planned to be reported by prior response.
Time frame: EOT (up to Week 48)
Population: Full analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T/PR + HAART Regimen (ATV/r-Based) | Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) | 55.6 percentage of participants |
| T/PR + HAART Regimen (EFV-Based) | Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) | 63.8 percentage of participants |
| T/PR + HAART Regimen (RAL-Based) | Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) | 61.0 percentage of participants |