HIV InfectionsPhase 2NCT00896051
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
A Phase 2 study testing Atazanavir (ATV) 300 mg, Atazanavir (ATV) 400 mg and Ritonavir (rtv) 100 mg in people with HIV Infections and Acquired Immunodeficiency Syndrome, run by Janssen R&D Ireland at 18 sites in 5 countries.
Trial summary
The purpose of this study is to determine the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) (PK) of ETR when given with ATV/rtv and 1 NRTI in treatment experienced HIV-1 infected patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Acquired Immunodeficiency Syndrome
- What is being tested?
- Atazanavir (ATV) 300 mg, Atazanavir (ATV) 400 mg and Ritonavir (rtv) 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 18 sitesin 5 countries
- Study dates
- Aug 2009to Apr 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
18 sites in 5 countries.
18 sites in 5 countries
United States10 sites
Study site
Bakersfield, California
Study site
Beverly Hills, California
Study site
Dallas, Texas
Study site
Houston, Texas
Study site
Little Rock, Arkansas
Study site
Macon, Georgia
Study site
Orlando, Florida
Study site
Tampa, Florida
Study site
Vero Beach, Florida
Study site
West Palm Beach, Florida
South Africa3 sites
Study site
Bloemfontein
Study site
Cape Town
Study site
George
About this study
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
The purpose of this study is to determine the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) (PK) of ETR when given with ATV/rtv and 1 NRTI in treatment experienced HIV-1 infected patients. In addition, safety, tolerability and anti-HIV effect of this regimen will also be studied. A total of 46 patients will be enrolled.
Read the detailed description
This is a randomized (study drug assigned by chance), exploratory, open-label (all involved people know the identity of the intervention) trial to evaluate the pharmacokinetics (PK), safety, tolerability and anti-HIV (anti Human Immunodeficiency Virus) activity of etravirine (ETR ) when given with atazanavir/ritonavir (ATV/rtv) and 1 nucleoside reverse transcriptase inhibitor (NRTI) in 46 treatment experienced HIV-1 infected patients. The trial will consist of : 4 weeks of Screening Period, 2 weeks Pre-Treatment Phase, 48-week Treatment Period, and a Final Visit followed by a 4-week Follow-up Period (only for patients not continuing treatment with ETR in another trial or program). Safety evaluations (AE reporting, labs, vital signs, etc.) will be monitored at each study visit. A PK substudy (included in the protocol, with optional participation) with tenofovir (TDF) added to the antiretroviral regimen for 7 days will be conducted in patients with > 24 weeks of treatment with suppressed HIV-1 viral load. In Pre-Treatment Phase, all patients will receive ATV/rtv 300/100 mg once daily to be taken following a meal each morning + 2 NRTIs (dose as specified in the labels) for 14 days. In Treatment Phase, patients will receive ETR 200 mg twice daily in addition to ATV/rtv (300/100 mg or 400/100 mg) once daily with meals + 1 investigator-selected NRTI for 48 weeks. In substudy TDF 300 mg once daily will be added to the treatment regimen x 7 days.
- Conditions
- HIV Infections, Acquired Immunodeficiency Syndrome
- Being tested
- Atazanavir (ATV) 300 mg, Atazanavir (ATV) 400 mg, Ritonavir (rtv) 100 mg, Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs), Etravirine (ETR) 200 mg
- Keywords
- HIV Infections, Acquired Immunodeficiency Syndrome, TMC125-TiDP2-C238, TMC125-C238, Etravirine, Intelence, HIV, HIV-1, Pharmacokinetics
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atazanavir (ATV) 300 mgDrug
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.
Atazanavir (ATV) 400 mgDrug
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.
Ritonavir (rtv) 100 mgDrug
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.
Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs)Drug
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.
Etravirine (ETR) 200 mgDrug
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.
Tenofovir disoproxil fumarate (TDF) 300 mgDrug
Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
| Study group | Role | What they receive |
|---|---|---|
| ATV/rtv 300/100 mg (Treatment A) | Experimental | 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). Receives: Drug: Atazanavir (ATV) 300 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 |
| ATV/rtv 400/100 mg (Treatment B) | Experimental | 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). Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
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).
Measured: Day -1 (Pretreatment); Week 2 (Test)
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
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).
Measured: Day -1 (Pretreatment); Week 2 (Test)
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)
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).
Measured: Day -1 (Reference); Week 2 (Test)
Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)
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).
Measured: Week 2
Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)
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).
Measured: Week 2
Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at 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).
Measured: Week 48
Secondary outcomes (7)
Change From Prebaseline in CD4+ Cell Count Over Time
The table below shows the mean change from prebaseline over time in CD4+ cell count using the Non-Completing = Failure (NC=F) imputation method.
Measured: Prebaseline, Baseline, Weeks 4, 12, 24, 48
The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method
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).
Measured: Baseline, Weeks 4, 12, 24, 48
The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method
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.
Measured: Baseline, Weeks 4, 12, 24, 48
The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method
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.
Measured: Week 48
Change From Pre-Baseline in Log10 Viral Load Over Time
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.
Measured: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48
Time to Confirmed Virologic Response
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.
Measured: Prebaseline to Week 48
Time to Virologic Failure
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.
Measured: Prebaseline to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2009 (estimated)
- Study startAug 2009
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen R&D Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen R&D Ireland Clinical Trial, Study director, Janssen R&D Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00896051
- Sponsor's protocol ID
- CR016045
- Other IDs
- TMC125-TiDP2-C238
- Status last verified
- Sep 2013
- First submitted
- 7 May 2009
- Last updated
- 30 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00896051
- Acronym / sponsor ID
- CR016045
- Conditions
- HIV Infections, Acquired Immunodeficiency Syndrome
- Keywords
- HIV Infections, Acquired Immunodeficiency Syndrome, TMC125-TiDP2-C238, TMC125-C238, Etravirine, Intelence, HIV, HIV-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Janssen R&D IrelandIndustry (pharma, biotech, devices)
- Study start
- Aug 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 11 May 2009 (estimated)
- Results
- Posted 30 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) (PK) of ETR when given with ATV/rtv and 1 NRTI in treatment experienced HIV-1 infected patients. In addition, safety, tolerability and anti-HIV effect of this regimen will also be studied. A total of 46 patients will be enrolled.
Detailed description
This is a randomized (study drug assigned by chance), exploratory, open-label (all involved people know the identity of the intervention) trial to evaluate the pharmacokinetics (PK), safety, tolerability and anti-HIV (anti Human Immunodeficiency Virus) activity of etravirine (ETR ) when given with atazanavir/ritonavir (ATV/rtv) and 1 nucleoside reverse transcriptase inhibitor (NRTI) in 46 treatment experienced HIV-1 infected patients. The trial will consist of : 4 weeks of Screening Period, 2 weeks Pre-Treatment Phase, 48-week Treatment Period, and a Final Visit followed by a 4-week Follow-up Period (only for patients not continuing treatment with ETR in another trial or program). Safety evaluations (AE reporting, labs, vital signs, etc.) will be monitored at each study visit. A PK substudy (included in the protocol, with optional participation) with tenofovir (TDF) added to the antiretroviral regimen for 7 days will be conducted in patients with > 24 weeks of treatment with suppressed HIV-1 viral load. In Pre-Treatment Phase, all patients will receive ATV/rtv 300/100 mg once daily to be taken following a meal each morning + 2 NRTIs (dose as specified in the labels) for 14 days. In Treatment Phase, patients will receive ETR 200 mg twice daily in addition to ATV/rtv (300/100 mg or 400/100 mg) once daily with meals + 1 investigator-selected NRTI for 48 weeks. In substudy TDF 300 mg once daily will be added to the treatment regimen x 7 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATV/rtv 300/100 mg (Treatment A) | Experimental | Drug: Atazanavir (ATV) 300 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 mgTreatment-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). |
| ATV/rtv 400/100 mg (Treatment B) | Experimental | 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 mgTreatment-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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atazanavir (ATV) 300 mgAtazanavir (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 | ATV/rtv 300/100 mg (Treatment A) |
| Atazanavir (ATV) 400 mgAtazanavir (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 | ATV/rtv 400/100 mg (Treatment B) |
| Ritonavir (rtv) 100 mgRitonavir (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 | ATV/rtv 300/100 mg (Treatment A), ATV/rtv 400/100 mg (Treatment B) |
| 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 | ATV/rtv 300/100 mg (Treatment A), ATV/rtv 400/100 mg (Treatment B) |
| Etravirine (ETR) 200 mgEtravirine (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 | ATV/rtv 300/100 mg (Treatment A), ATV/rtv 400/100 mg (Treatment B) |
| Tenofovir disoproxil fumarate (TDF) 300 mgTenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7. | Drug | ATV/rtv 300/100 mg (Treatment A), ATV/rtv 400/100 mg (Treatment B) |
Primary outcome
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).
7 secondary outcomes
Change From Prebaseline in CD4+ Cell Count Over Time
Time frame: Prebaseline, Baseline, Weeks 4, 12, 24, 48
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 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 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
Change From Pre-Baseline in Log10 Viral Load Over Time
Time frame: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48
Time to Confirmed Virologic Response
Time frame: Prebaseline to Week 48
Time to Virologic Failure
Time frame: Prebaseline to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen R&D Ireland Clinical Trial study director
Janssen R&D Ireland
18 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atazanavir (ATV) 300 mg, Atazanavir (ATV) 400 mg and Ritonavir (rtv) 100 mg in people with HIV Infections and Acquired Immunodeficiency Syndrome, run by Janssen R&D Ireland at 18 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, South Africa, Argentina, France, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2013.