Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection
Information source: University of North Carolina, Chapel Hill
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Etravirine (Intelence) (Drug)
Phase: Phase 2
Sponsored by: University of North Carolina, Chapel Hill
Official(s) and/or principal investigator(s):
Michelle Floris-Moore, MD, MS, Principal Investigator, Affiliation: University of North Carolina, Chapel Hill
Susan Pedersen, RN, BSN, Phone: 919-966-6713, Email: firstname.lastname@example.org
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.
Official title: Antiretroviral Activity and Tolerability of Once Daily Etravirine in Treatment-Naïve Adults With HIV-1 Infection
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To estimate the antiretroviral activity of etravirine 400 mg given once daily, with fixed-dose Truvada once daily, among treatment-naÃ¯ve HIV-1 infected adults as measured by the proportion of participants with HIV RNA < 50 copies/mL at Week 24.
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.
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.
To assess change in CD4+ cell count from baseline to Weeks 24, 48 and 96 of treatment with etravirine and fixed-dose tenofovir/emtricitabine.
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.
To assess population pharmacokinetics of etravirine 400 mg once daily, in combination with fixed-dose emtricitabine-tenofovir among treatment-naÃ¯ve HIV-1 infected adults.
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.
To assess tolerability of etravirine in HIV-1 infected adults initiating antiretroviral therapy.
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.
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.
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.
Minimum age: 18 Years.
Maximum age: N/A.
- 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
- Plasma HIV-1 RNA â‰¥ 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 Î²-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 â‰¥ 7. 5 g/dL within 45 days prior to study entry.
- Absolute neutrophil count â‰¥ 500/mmÂ³ within 45 days prior to study entry.
- Platelets â‰¥ 50,000/mmÂ³ within 45 days prior to study entry.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) â‰¤ 3X ULN or
bilirubin â‰¤ 2. 5 ULN within 45 days prior to study entry.
- GFR > 59 as calculated by MDRD within 45 days prior to study entry.
- Prior receipt of etravirine, dapivirine (TMC120), or rilpivirine (TMC 278).
- 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.
- 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
- 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
- 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
Locations and Contacts
Susan Pedersen, RN, BSN, Phone: 919-966-6713, Email: email@example.com
The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7215, United States; Recruiting
Donna Pittard, RN, BSN, Phone: 919-843-6512, Email: firstname.lastname@example.org
David Ragan, RN, BSN, Phone: 919-966-2623, Email: email@example.com
Michelle Floris-Moore, MD, MS, Principal Investigator
Joseph Eron, MD, Sub-Investigator
David Wohl, MD, Sub-Investigator
Kristine Patterson, MD, Sub-Investigator
Angela Kashuba, PharmD, Sub-Investigator
Carolinas Medical Center, Charlotte, North Carolina 28207, United States; Recruiting
Jessica Kearney-Bryan, RN, BSN, Phone: 704-355-0244, Email: firstname.lastname@example.org
Marc A Johnson, MD, Principal Investigator
Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, United States; Recruiting
Melissa Trader, Phone: 336-716-8918, Email: email@example.com
Liby Mosley, Phone: 336-716-3266, Email: firstname.lastname@example.org
Aimee M Wilkin, MD, MPH, Principal Investigator
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Starting date: September 2009
Last updated: June 2, 2011