Clinical trial NCT00896051
Conditions: HIV Infections Acquired Immunodeficiency Syndrome
Keywords: HIV Infections Acquired Immunodeficiency Syndrome TMC125-TiDP2-C238 TMC125-C238 Etravirine Intelence HIV HIV-1 Pharmacokinetics
Sponsor: Janssen R&D Ireland
Start date: 2009-08-01; Completion date: 2012-04-01
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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. 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.

Arms: arm 1: 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). arm 2: 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).
Interventions: intervention 1: Atazanavir (ATV) 300 mg intervention 2: Atazanavir (ATV) 400 mg intervention 3: Ritonavir (rtv) 100 mg intervention 4: Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs) intervention 5: Etravirine (ETR) 200 mg intervention 6: Tenofovir disoproxil fumarate (TDF) 300 mg
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: 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. intervention 5: 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. intervention 6: Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.

Protocol documents: