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

NCT00959894 | Completed Phase 2 Results DMC

• 1 other identifier: 08-2070
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV; Infection; Treatment Naive; Adults; Once; Daily; Etravirine; HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24

  The primary study endpoint was the proportion of participants who achieved HIV-1 RNA \<50 copies/ml at Week 24 of study participation. The per-protocol primary analysis was conducted intention-to-treat, with missing evaluations counted as failures. Achievement of HIV-1 viral load below 50 copies/ml was defined as having HIV-1 RNA \<50 copies/ml during the Week 24 analysis window (\>18 and \<30 weeks post-entry).

  24 weeks

Secondary Outcomes (24)

• The Proportion of Participants With HIV RNA <50 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

  48 weeks

• The Proportion of Participants With HIV RNA <50 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

  96 weeks

• The Proportion of Participants With HIV RNA <200 Copies/mL at Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

  24 weeks

• The Proportion of Participants With HIV RNA <200 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

  48 weeks

• The Proportion of Participants With HIV RNA <200 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

  96 weeks

Study Arms (1)

Etravirine 400 mg once daily

EXPERIMENTAL

Etravirine 400 mg once daily with fixed dose tenofovir/emtricitabine (Truvada) one tablet once daily

Drug: Etravirine (Intelence); Drug: Truvada

Interventions

Etravirine (Intelence) DRUG

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

Also known as: TMC-125, Intelence

Etravirine 400 mg once daily

Truvada DRUG

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

Also known as: Tenofovir/emtricitabine

Etravirine 400 mg once daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 clinical laboratory improvement amendments (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-human chorionic gonadotropin (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 upper limit of normal (ULN) or bilirubin ≤ 2.5 ULN within 45 days prior to study entry.
• Glomerular filtration rate (GFR) \> 59 as calculated by Modification of Diet in Renal Disease (MDRD) equation within 45 days prior to study entry.

You may not qualify if:

• 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:
• Any of the following nonnucleoside reverse transcriptase inhibitor (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.
• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (3)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7215, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (13)

• Gruzdev B, Rakhmanova A, Doubovskaya E, Yakovlev A, Peeters M, Rinehart A, de Dier K, Baede-Van Dijk P, Parys W, van 't Klooster G. A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects. AIDS. 2003 Nov 21;17(17):2487-94. doi: 10.1097/00002030-200311210-00011.

  PMID: 14600520 BACKGROUND

• TMC125-C223 Writing Group; Nadler JP, Berger DS, Blick G, Cimoch PJ, Cohen CJ, Greenberg RN, Hicks CB, Hoetelmans RM, Iveson KJ, Jayaweera DS, Mills AM, Peeters MP, Ruane PJ, Shalit P, Schrader SR, Smith SM, Steinhart CR, Thompson M, Vingerhoets JH, Voorspoels E, Ward D, Woodfall B. Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS. 2007 Mar 30;21(6):F1-10. doi: 10.1097/QAD.0b013e32805e8776.

  PMID: 17413684 BACKGROUND

• Shikuma CM, Yang Y, Glesby MJ, Meyer WA 3rd, Tashima KT, Ribaudo HJ, Webb N, Bastow B, Kuritzkes DR, Gulick RM. Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095). J Acquir Immune Defic Syndr. 2007 Apr 15;44(5):540-50. doi: 10.1097/QAI.0b013e318031d5a0.

  PMID: 17245230 BACKGROUND

• Madruga JV, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, Pialoux G, Wilkin T, Peeters M, Vingerhoets J, de Smedt G, Leopold L, Trefiglio R, Woodfall B; DUET-1 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007 Jul 7;370(9581):29-38. doi: 10.1016/S0140-6736(07)61047-2.

  PMID: 17617270 BACKGROUND

• Lazzarin A, Campbell T, Clotet B, Johnson M, Katlama C, Moll A, Towner W, Trottier B, Peeters M, Vingerhoets J, de Smedt G, Baeten B, Beets G, Sinha R, Woodfall B; DUET-2 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007 Jul 7;370(9581):39-48. doi: 10.1016/S0140-6736(07)61048-4.

  PMID: 17617271 BACKGROUND

• Ghosn J, Chaix ML, Peytavin G, Rey E, Bresson JL, Goujard C, Katlama C, Viard JP, Treluyer JM, Rouzioux C. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS. 2004 Sep 24;18(14):1958-61. doi: 10.1097/00002030-200409240-00014.

  PMID: 15353984 BACKGROUND

• Reddy YS, Gotzkowsky SK, Eron JJ, Kim JY, Fiske WD, Fiscus SA, Petch L, Cohen MS, Kashuba AD. Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1-infected men. J Infect Dis. 2002 Nov 1;186(9):1339-43. doi: 10.1086/344311. Epub 2002 Oct 7.

  PMID: 12402205 BACKGROUND

• Taylor S, Reynolds H, Sabin CA, Drake SM, White DJ, Back DJ, Pillay D. Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men. AIDS. 2001 Oct 19;15(15):2051-3. doi: 10.1097/00002030-200110190-00022.

  PMID: 11600838 BACKGROUND

• van Praag RM, Repping S, de Vries JW, Lange JM, Hoetelmans RM, Prins JM. Pharmacokinetic profiles of nevirapine and indinavir in various fractions of seminal plasma. Antimicrob Agents Chemother. 2001 Oct;45(10):2902-7. doi: 10.1128/AAC.45.10.2902-2907.2001.

  PMID: 11557488 BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 144-week data released on Gilead's study 934. AIDS Patient Care STDS. 2007 Aug;21(8):603-4. No abstract available.

  PMID: 17902243 BACKGROUND

• Floris-Moore MA, Mollan K, Wilkin AM, Johnson MA, Kashuba AD, Wohl DA, Patterson KB, Francis O, Kronk C, Eron JJ. Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Antivir Ther. 2016;21(1):55-64. doi: 10.3851/IMP2982. Epub 2015 Aug 11.

  PMID: 26263403 DERIVED

MeSH Terms

Conditions

HIV Infections; Infections

Interventions

etravirine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Michelle Floris-Moore, M.D., M.S.
• Organization: UNC School of Medicine

mfloris@med.unc.edu

919-966-2537

Study Officials

• Michelle Floris-Moore, MD, MS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: August 14, 2009
• First Posted: August 17, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 6, 2016
• Results First Posted: May 13, 2015

Record last verified: 2016-04

Locations

US (3)