Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection

This study has been completed.
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Michelle Floris-Moore, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00959894
First received: August 14, 2009
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

The main study is a single arm, open-label, prospective study to assess antiretroviral activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in genital secretions when subjects are taking etravirine. The purpose of the metabolic sub-study is to learn about the effects of etravirine on body composition, as well as lipid and glucose levels.


Condition Intervention Phase
HIV Infections
Drug: Etravirine (Intelence)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antiretroviral Activity and Tolerability of Once Daily Etravirine in Treatment-Naïve Adults With HIV-1 Infection

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • To estimate the antiretroviral activity of etravirine 400 mg given once daily, with fixed-dose Truvada once daily, among treatment-naïve HIV-1 infected adults as measured by the proportion of participants with HIV RNA < 50 copies/mL at Week 24. [ Time Frame: August 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the proportion of participants with HIV RNA <50 copies/mL at Week 48 and Week 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess the proportion of participants with HIV RNA <200 copies/mL at Weeks 24, 48, and 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess change in CD4+ cell count from baseline to Weeks 24, 48, and 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess resistance mutations in the subset of patients with virologic failure while on etravirine and fixed-dose tenofovir/emtricitabine who have HIV RNA >500 copies/mL and genotype resistance results. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess population pharmacokinetics of etravirine 400 mg once daily, in combination with fixed-dose emtricitabine-tenofovir among treatment-naïve HIV-1 infected adults. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess pharmacokinetics of etravirine in genital secretions of up to 10 men and up to 10 women at Week 4 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: August 2010 ] [ Designated as safety issue: No ]
  • To assess tolerability of etravirine in HIV-1 infected adults initiating antiretroviral therapy. [ Time Frame: January 2012 ] [ Designated as safety issue: Yes ]
  • To assess change in the lipid profile and glucose metabolism, in a subgroup of up to 40 participants, from baseline to Weeks 24, 48, and 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To assess change in limb and trunk fat distribution as measured by DEXA scan, in the same subgroup of up to 40 participants (as in Aim 8), from baseline to Weeks 24 and 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: September 2009
Study Completion Date: May 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etravirine 400 mg once daily
Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily
Drug: Etravirine (Intelence)
Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day
Other Names:
  • TMC-125
  • Intelence
  • Tenofovir/emtricitabine
  • Truvada

Detailed Description:

Participants: There will be approximately 80 HIV-1-infected men and women aged 18 years or older who have taken less than or equal to 10 days of prior antiretroviral therapy and have never taken etravirine, dapivirine (TMC120), or rilpivirine (TMC 278) in the main study. There will be approximately 40 subjects who enroll in the main study that will be in the metabolic sub-study and approximately 20 subjects (10 pre-menopausal women and 10 men) who enroll in the main study that will be in the genital secretions PK sub-study.

Procedures (methods): For the main study subjects will take etravirine 400 mg once daily orally with fixed-dose tenofovir/emtricitabine (Truvada) one tablet once daily. For the genital secretions PK sub-study, genital secretion samples will be self-collected throughout the study except for the week 4 study visit where women will have the cervicovaginal sample at time 0 and at 24 hours collected by study staff. For the metabolic sub-study, waist measurements and DEXA scans will be performed at entry, week 24, and week 96, and 2-3 teaspoons of blood to check lipids, insulin, and glucose will be taken at entry and weeks 12, 24, 48, and 96.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection as documented by any licensed ELISA test and confirmed by Western Blot or other confirmatory test at any time prior to study entry. Acceptable alternative confirmatory tests are plasma HIV-1 RNA, HIV-1 culture, HIV-1 antigen, or a second antibody test by a method other than ELISA. Alternatively, if an HIV-antibody test result is not available, two HIV-1 RNA values >2000 copies/mL, drawn at least 24 hours apart, performed by any laboratory that has CLIA certification, or its equivalent, may be used to document infection.
  • Age 18 years or older.
  • Able to provide informed consent.
  • In the opinion of the investigator, able to comply with study medication and procedures.
  • Plasma HIV-1 RNA ≥ 1000 copies/mL as measured by any FDA-approved test for quantifying HIV-1 RNA within 90 days prior to study entry.
  • Less than or equal to 10 days of cumulative exposure to antiretroviral therapy.
  • For all women of reproductive potential, a negative urine or serum β-HCG pregnancy test performed within 48 hours prior to study entry.

    • All study volunteers, both male and female, must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) while receiving study medications and for 6 weeks after stopping study medications.
    • If participating in sexual activity that could lead to conception, study volunteers must agree to use at least one method of reliable contraception which must be a barrier method (i.e., a condom without spermicide, a diaphragm, or cervical cap) throughout the study and for 6 weeks thereafter.

NOTE: Acceptable documentation of lack of reproductive potential for a woman is self-reported history of being postmenopausal for at least 24 months, or having had surgical sterilization (hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation) or of male partner's azoospermia. Acceptable documentation for a man is self-reported history of azoospermia.

  • Hemoglobin ≥ 7.5 g/dL within 45 days prior to study entry.
  • Absolute neutrophil count ≥ 500/mm³ within 45 days prior to study entry.
  • Platelets ≥ 50,000/mm³ within 45 days prior to study entry.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3X ULN or bilirubin ≤ 2.5 ULN within 45 days prior to study entry.
  • GFR > 59 as calculated by MDRD within 45 days prior to study entry.

Exclusion Criteria:

  • Prior receipt of etravirine, dapivirine, or rilpivirine (Edurant), or Complera.
  • Evidence of any of the resistance-associated mutations listed below on genotype testing performed within 90 days of study entry. Any pending resistance testing ordered prior to study entry must be available for review by the investigator prior to enrollment. Major resistance mutations include:

    1. Any of the following NNRTI mutations: V90I, A98G, L100I, K101E/H/P/Q, K103H/S/T, V106A/I/M, V108I, E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T, K103N.
    2. Any of the following NRTI mutations: M184V/I, K70E/R, K65R, M41L, 69 insert, L210W, T215Y/F, K219Q/E, L74V.
  • Pregnancy
  • Breastfeeding
  • Any condition which, in the opinion of the investigator, would be likely to interfere with ability to take the study medications appropriately and comply with the study protocol.
  • Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 30 days prior to study entry.

NOTE: Routine standard of care, including hepatitis B, influenza, pneumococcus, and tetanus vaccines are permitted.

  • Current active illness requiring systemic treatment and/or hospitalization until the individual completes therapy or, in the opinion of the investigator, is clinically stable on therapy for at least 7 days prior to study entry.
  • Life expectancy of less than 6 months.
  • Acute viral hepatitis.
  • Known allergy/hypersensitivity to components of the study drugs or their formulations.
  • Use of any medications that are prohibited during the study period (see Section 8.1 of the protocol - Prohibited Medications).
  • Refusal by an individual who is taking anti-depressant medications to allow the investigator or Primary HIV Care provider to communicate with his/her psychiatrist/Mental Health clinician regarding the initiation of study medications in those cases where co-administration of study drugs may alter anti-depressant drug levels.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00959894

Locations
United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7215
Carolinas Medical Center
Charlotte, North Carolina, United States, 28207
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Janssen Pharmaceuticals
Investigators
Principal Investigator: Michelle Floris-Moore, MD, MS University of North Carolina, Chapel Hill
  More Information

Publications:
Scholler-Gyure M, Kakuda TN, De Smedt G, Woodfall B, Lachaert R, Beets G, Peeters M, Hoetelmans RM. Pharmacokinetics of TMC125 in once- and twice- daily regimens in HIV-1-negative volunteers. Program and Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2007 [Abstract A-1427], Chicago IL.
Lalezari J, et al. Pharmacokinetics of once-daily etravirine (ETR) without and with once-daily darunavir/ritonavir (DRV/r) in antiretroviral-naïve HIV-1 infected adults. 9th International Congress on Drug Therapy in HIV Infection 2008; abstract O413.

Responsible Party: Michelle Floris-Moore, MD, Clinical Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00959894     History of Changes
Other Study ID Numbers: 08-2070
Study First Received: August 14, 2009
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
HIV
Infection
Treatment Naive
Adults
Once
Daily
Etravirine
HIV-1 Infection

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Etravirine
Tenofovir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014