Clinical trial NCT00896051: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Keywords: HIV Infections
Acquired Immunodeficiency Syndrome
TMC125-TiDP2-C238
TMC125-C238
Etravirine
Intelence
HIV
HIV-1
Pharmacokinetics
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2009-05-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
timeFrame: Day -1 (Pretreatment); Week 2 (Test)
measure: Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
timeFrame: Day -1 (Pretreatment); Week 2 (Test)
measure: Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)
timeFrame: Day -1 (Reference); Week 2 (Test)
measure: Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)
timeFrame: Week 2
measure: Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)
timeFrame: Week 2
measure: Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Change From Prebaseline in CD4+ Cell Count Over Time
timeFrame: Prebaseline, Baseline, Weeks 4, 12, 24, 48
measure: The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method
timeFrame: Baseline, Weeks 4, 12, 24, 48
measure: The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method
timeFrame: Baseline, Weeks 4, 12, 24, 48
measure: The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method
timeFrame: Week 48
measure: Change From Pre-Baseline in Log10 Viral Load Over Time
timeFrame: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48
measure: Time to Confirmed Virologic Response
timeFrame: Prebaseline to Week 48
measure: Time to Virologic Failure
timeFrame: Prebaseline to Week 48
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Bakersfield
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Macon
country: United States
state: Georgia
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Paris Cedex 10
country: France
city: Paris
country: France
city: Tourcoing
country: France
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: George
country: South Africa
city: Bangkok
country: Thailand
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References: