A Two Year Study of the Clinical Efficacy of the Combination of Emtricitabine, Tenofovir, and Nevirapine
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cell Cycle Independent Antiretroviral Therapy: Combination of Nevirapine, FTC, and Tenofovir|
- The primary endpoint will be evidence of viral failure as determined by two consecutive viral load measurements of >500 copies/ml. [ Time Frame: In this study, a virologic failure is defined as failure to reach a viral load <500 copies/ml at the week 24 visit, or having 2 consecutive viral loads >500 copies/ml after week 24 ] [ Designated as safety issue: Yes ]
- proportion of patients with grade 2, 3 and 4 adverse events and laboratory toxicities [ Time Frame: Protocol length is 96 weeks ] [ Designated as safety issue: Yes ]
- proportion of patients with plasma HIV RNA < 50 copies/mL [ Time Frame: 96 weeks. ] [ Designated as safety issue: Yes ]
- proportion of patients with plasma HIV RNA < 400 copies/mL [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
- change from baseline in plasma HIV RNA at 24, 48, 72, and 96 weeks [ Time Frame: Weeks 24, 48, 72,96 ] [ Designated as safety issue: Yes ]
- changes in CD4 cell counts, in each group, from baseline, and at weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72, 96 ] [ Designated as safety issue: Yes ]
- changes in Mitochondrial DNA to Cellular DNA ratio [ Time Frame: Weeks 24, 48, 72, 96 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2004|
|Study Completion Date:||July 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Drug: Nevirapine, FTC, and Tenofovir
Description of study design This is an open-labeled clinical trial evaluating an antiretroviral treatment regimen in which the drugs have demonstrated in vitro activity in both, resting and activated mononuclear cells. These drugs include: FTC 200 mg p.o. qd, and Tenofovir 300 mg p.o. qd, and Nevirapine 200 mg b.i.d.
Eligible patients must be at least 18 years of age, be referred by their primary HIV provider for antiretroviral therapy or if the patient is self referred, have a CD4 cell count of < 250/mm3 and have a viral load >5,000c/ml. Eligibility requirement for women is that they must have a CD4 cell count of <250 at the time of enrollment. This cutoff for women is based on unpublished data that there may be increased hepatotoxicity in women with a CD4 cell count > 250 cell/mm3. The screening evaluation will take place the day the informed consent is signed. During that screening evaluation, the patient will undergo a history and physical examination, and will have study labs drawn. Within 60 days of the screening evaluation and meeting all eligible criteria, the patient will be placed on the study treatment regimen. Patients will be evaluated at the clinic on Day 0 (therapy initiation), weeks 2, 4, 6, 8, 12, 16, and then every 8 weeks until 48 weeks and thereafter every 12 weeks through week 96. At the end of the study, all patients may continue their current antiretroviral treatment regimen at the discretion of the patient and their primary care provider.
Pharmacokinetic Analysis Sub Study A pharmacokinetic evaluation will be performed in first 7 volunteers to assess the impact of FTC on Nevirapine and vice versa. Pharmacokinetic analysis will be performed at end of week 2 ( day 14) during 200mg qd start up period. Samples will be obtained at baseline and 1, 3, 6, 12 and 24 hours post Nevirapine dosing. Pharmacokinetic analysis will be repeated at the week 8 visit. Samples will be obtained at baseline and 1, 3, 6, 12 and 24 hours post Nevirapine.
Assignment of patients There will be 60 patients involved in this clinical trial. This is an open-labeled study. There are no placebos involved in this study.
Dose and dose selection The dosages of medications are those that are currently used as standard clinical practice: Nevirapine 200 mg b.i.d. (1-200 mg tablet b.i.d.); Emtricitabine (FTC) 200mg po qd.(1-200mg capsule); Tenofovir 300 mg once-a-day (1-300 mg tablet qd).
Justification of study design All study patients require treatment for their HIV infection. All of the drugs used in this study are FDA-Approved. Tenofovir and FTC are approved as a once-a-day treatment medication. Nevirapine (NVP) is approved for BID dosing.
NOTE: That whenever Nevirapine is being prescribed, there will be a lead-in period of 14 days in which Nevirapine will be prescribed as 200 mg once a day followed by 200 mg BID as is the recommended standard of care.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00344461
|United States, Maryland|
|University of Maryland, Institute of Human Virology|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Robert R Redfield, MD||University of Maryland, School of Medicine, IHV|
|Principal Investigator:||Charles E Davis, MD||University of Maryland, School of Medicine, IHV|