TMC125-TiDP2-C238: An Exploratory Pharmacokinetics, Safety and Anti-HIV Activity Study of Etravirine (ETR) When Given With Boosted Atazanavir (ATV/Rtv) at Two Different Doses and 1 Nucleoside Reverse Transcriptase Inhibitor (NRTI) in Treatment Experienced HIV Patients
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ClinicalTrials.gov Identifier: NCT00896051 |
Recruitment Status
:
Completed
First Posted
: May 11, 2009
Results First Posted
: September 30, 2013
Last Update Posted
: September 30, 2013
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Condition or disease | Intervention/treatment | Phase |
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HIV Infections Acquired Immunodeficiency Syndrome | Drug: Atazanavir (ATV) 300 mg Drug: Atazanavir (ATV) 400 mg Drug: Ritonavir (rtv) 100 mg Drug: Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs) Drug: Etravirine (ETR) 200 mg Drug: Tenofovir disoproxil fumarate (TDF) 300 mg | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 50 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | TMC125-TiDP2-C238: A Randomized, Exploratory, Open-label 48-week Trial to Investigate the Pharmacokinetics, Safety, Tolerability and Antiviral Activity of Etravirine (ETR) in Combination With Ritonavir-boosted Atazanavir (ATV/Rtv) and 1 NRTI in Treatment-experienced HIV-1 Infected Subjects |
Study Start Date : | August 2009 |
Actual Primary Completion Date : | April 2012 |
Actual Study Completion Date : | April 2012 |

Arm | Intervention/treatment |
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Experimental: ATV/rtv 300/100 mg (Treatment A)
Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants will take by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks pre-treatment followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. If particpating in an optional substudy to assess the effect of adding tenofovir disoproxil fumarate (TDF) for 7 days on ATV and ETR pharmacokinetics, participants will receive TDF 300 mg once daily for 7 days in addition to their antiretroviral regimen (ETR+ATV/rtv+NRTI).
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Drug: Atazanavir (ATV) 300 mg
Atazanavir (ATV) 300 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 300 mg by mouth following a meal each morning on Substudy Days -1 to 7.
Drug: Ritonavir (rtv) 100 mg
Ritonavir (rtv) 100 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take rtv 100 mg by mouth following a meal each morning on Substudy Days -1 to 7.
Drug: Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs)
2 investigator-selected NRTIs taken as specified in the individual product labels for 2 weeks during the Pre-Treatment Period followed by 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) taken as specified in the individual product label for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) mg taken as specified in the individual product label during the Substudy.
Drug: Etravirine (ETR) 200 mg
Etravirine (ETR) 200 mg taken twice daily as two 100-mg tablets following a meal (morning and evening) for at least the first two weeks of the 48-week Treatment Period. If participating in the optional substudy, participants will take ETR 200 mg twice daily as two 100-mg tablets following a meal each morning and evening on Substudy Days -1 to 7.
Drug: Tenofovir disoproxil fumarate (TDF) 300 mg
Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
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Experimental: ATV/rtv 400/100 mg (Treatment B)
Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants will take by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks pretreatment followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. If particpating in an optional substudy to assess the effect of adding tenofovir disoproxil fumarate (TDF) for 7 days on ATV and ETR pharmacokinetics, participants will take TDF 300 mg once daily for 7 days in addition to their antiretroviral regimen (ETR+ATV/rtv+NRTI).
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Drug: Atazanavir (ATV) 400 mg
Atazanavir (ATV) 400 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 400 mg by mouth following a meal each morning on Substudy Days -1 to 7.
Drug: Ritonavir (rtv) 100 mg
Ritonavir (rtv) 100 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take rtv 100 mg by mouth following a meal each morning on Substudy Days -1 to 7.
Drug: Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs)
2 investigator-selected NRTIs taken as specified in the individual product labels for 2 weeks during the Pre-Treatment Period followed by 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) taken as specified in the individual product label for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) mg taken as specified in the individual product label during the Substudy.
Drug: Etravirine (ETR) 200 mg
Etravirine (ETR) 200 mg taken twice daily as two 100-mg tablets following a meal (morning and evening) for at least the first two weeks of the 48-week Treatment Period. If participating in the optional substudy, participants will take ETR 200 mg twice daily as two 100-mg tablets following a meal each morning and evening on Substudy Days -1 to 7.
Drug: Tenofovir disoproxil fumarate (TDF) 300 mg
Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
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- Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) [ Time Frame: Day -1 (Pretreatment); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax).
- Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr) [ Time Frame: Day -1 (Pretreatment); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax).
- Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr) [ Time Frame: Day -1 (Reference); Week 2 (Test) ]The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
- Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) [ Time Frame: Week 2 ]The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin) and maximum plasma concentration (Cmax).
- Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr) [ Time Frame: Week 2 ]The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the area under the plasma concentration-time curve from time of intake to 12 hours after dosing (AUC12hr).
- Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48 [ Time Frame: Week 48 ]The table below shows the percentage of participants wih undetectable plasma viral load (VL) values (<50 copies/mL) at Week 48 using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their baseline value, thus resulting in a 0 change).
- Change From Prebaseline in CD4+ Cell Count Over Time [ Time Frame: Prebaseline, Baseline, Weeks 4, 12, 24, 48 ]The table below shows the mean change from prebaseline over time in CD4+ cell count using the Non-Completing = Failure (NC=F) imputation method.
- The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method [ Time Frame: Baseline, Weeks 4, 12, 24, 48 ]The table below shows the percentage of participants per time point with a virologic response defined as having a plasma viral load (VL) <50 copies/mL, and with plasma VL <400 copies/mL using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their Baseline value, thus resulting in a 0 change).
- The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method [ Time Frame: Baseline, Weeks 4, 12, 24, 48 ]The table below shows the percentage of participants with a virologic response defined as a viral load <50 Copies/mL and <400 Copies/mL per time point calculated using the time to loss of virologic response (TLOVR) imputation method.
- The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method [ Time Frame: Week 48 ]The table below provides the results from the snapshot analysis method that includes the percentage of participants with virologic response (<50 copies/mL), the percentage of participants who were virologic failures (VF) (>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load >50 copies/mL), and the percentage of participants with no viral load (VL) data available at Week 48.
- Change From Pre-Baseline in Log10 Viral Load Over Time [ Time Frame: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48 ]The table below shows the mean change from prebaseline over time in log10 (Copies/mL) plasma viral load using the Non-Completing = Failure (NC=F) imputation method.
- Time to Confirmed Virologic Response [ Time Frame: Prebaseline to Week 48 ]The table below provides the time in days it took participants to reach a confirmed virologic response defined as a plasma viral load (VL) <50 copies/mL, and plasma VL <400 copies/mL analyzed according to the Time to Loss of Virologic Response (TLOVR) imputation method.
- Time to Virologic Failure [ Time Frame: Prebaseline to Week 48 ]The table below shows the number of days to virologic failure defined as a plasma viral load (VL) > 50 copies/mL for participants who had been virologic responders (ie, having a plasma VL <50, and <400 copies/mL according to the time to loss of virologic response [TLOVR] imputation method). Time to virologic failure was the time to subsequent loss of virologic response, and the time was calculated from Prebaseline (Week -2). Participants who never achieved a virologic response were defined as nonresponders and counted as virologic failures on Day 1.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Documented HIV-1 infection
- Failing on a stable ART (anti retroviral therapy) with HIV-1 plasma viral load above 500 HIV-1 RNA copies/ml
- Presence of at least 1 documented NNRTI mutation
- Demonstrated sensitivity to ATV, ETR and at least one of the selected NRTIs based on the resistance test at screening
- General medical condition, in the investigator's opinion, does not interfere with the assessments and completion of the trial
- Substudy: patients who have been treated in C238 for more than 24 weeks and are currently suppressed (defined as patients with at least 2 most recent and consecutive viral loads less than 50 cp/mL) will be considered eligible for the substudy
Exclusion Criteria:
- Primary HIV-1 infection
- Previously documented HIV-2 infection
- Previously failed 2 or more HIV PI-containing regimens
- Previous diagnosis of hereditary hyperbilirubinemia (eg. Gilbert's syndrome, Crigler-Najjar syndrome).
Grade 3 or 4 toxicities (according to DAIDS grading)
- Acute and chronic viral hepatitis
- Receipt of an investigational drug or investigational vaccine within 30 days prior to the trial drug administration
- Pregnant or breastfeeding female

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00896051
United States, Arkansas | |
Little Rock, Arkansas, United States | |
United States, California | |
Bakersfield, California, United States | |
Beverly Hills, California, United States | |
United States, Florida | |
Orlando, Florida, United States | |
Tampa, Florida, United States | |
Vero Beach, Florida, United States | |
West Palm Beach, Florida, United States | |
United States, Georgia | |
Macon, Georgia, United States | |
United States, Texas | |
Dallas, Texas, United States | |
Houston, Texas, United States | |
Argentina | |
Buenos Aires, Argentina | |
Cordoba, Argentina | |
France | |
Paris Cedex 10, France | |
Paris, France | |
Tourcoing, France | |
South Africa | |
Bloemfontein, South Africa | |
Cape Town, South Africa | |
George, South Africa | |
Thailand | |
Bangkok, Thailand |
Study Director: | Janssen R&D Ireland Clinical Trial | Janssen R&D Ireland |
Responsible Party: | Janssen R&D Ireland |
ClinicalTrials.gov Identifier: | NCT00896051 History of Changes |
Other Study ID Numbers: |
CR016045 TMC125-TiDP2-C238 ( Other Identifier: Janssen R&D Ireland ) |
First Posted: | May 11, 2009 Key Record Dates |
Results First Posted: | September 30, 2013 |
Last Update Posted: | September 30, 2013 |
Last Verified: | September 2013 |
Keywords provided by Janssen R&D Ireland:
HIV Infections Acquired Immunodeficiency Syndrome TMC125-TiDP2-C238 TMC125-C238 Etravirine |
Intelence HIV HIV-1 Pharmacokinetics |
Additional relevant MeSH terms:
HIV Infections Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immune System Diseases Slow Virus Diseases Ritonavir Atazanavir Sulfate Tenofovir |
Etravirine Reverse Transcriptase Inhibitors HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors |