DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: Janssen R&D Ireland
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections; Acquired Immunodeficiency Syndrome

Intervention: 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 (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Janssen R&D Ireland

Official(s) and/or principal investigator(s):
Janssen R&D Ireland Clinical Trial, Study Director, Affiliation: Janssen R&D Ireland

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)

Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)

Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)

Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)

Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)

Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)

Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)

Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)

Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)

Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)

Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48

Secondary outcome:

Change From Prebaseline in CD4+ Cell Count Over Time

The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method

The Percentage of Participants With a Virologic Response 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

Change From Pre-Baseline in Log10 Viral Load Over Time

Time to Confirmed Virologic Response

Time to Virologic Failure

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Buenos Aires, Argentina

Cordoba, Argentina

Paris Cedex 10, France

Paris, France

Tourcoing, France

Bloemfontein, South Africa

Cape Town, South Africa

George, South Africa

Bangkok, Thailand

Little Rock, Arkansas, United States

Bakersfield, California, United States

Beverly Hills, California, United States

Orlando, Florida, United States

Tampa, Florida, United States

Vero Beach, Florida, United States

West Palm Beach, Florida, United States

Macon, Georgia, United States

Dallas, Texas, United States

Houston, Texas, United States

Additional Information

Starting date: August 2009
Last updated: September 27, 2013

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017