A Multicenter, Randomized, Open-Label, Active-Controlled Pilot Study to Evaluate theSafety and Antiretroviral Activity of Unboosted Atazanavir BID Plus Raltegravir BID and Boosted Atazanavir QD in Combination with Tenofovir/Emtricitabine QD in Treatment Naive HIV-Infected Subjects
- Conditions
- HIV, COMBINATION THERAPYMedDRA version: 9.1Level: LLTClassification code 10020161Term: HIV infection
- Registration Number
- EUCTR2008-003364-19-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
Signed Written Informed Consent
1) Freely given informed consent must be obtained from subjects prior to clinical trial
participation, including informed consent for any screening procedures conducted to
establish subject eligibility for the trial;
Target Population
2) Screening HIV-1 RNA = 5000 c/mL
3) Screening CD4 cell count meeting one of the following criteria:
a) < 350 cells/mm³
b) Screening CD4 = 50 and = 500 cells/mm³ ONLY if at least one of the following
conditions apply:
i) Screening HIV RNA > 100,000 c/mL , or
ii) CD4 decline > 50 - 100 cells/mm³/year, or
iii) age = 55 years
c) Any CD4 cell count if subject has a history of an AIDS defining illness (see
Protocol Appendix 7)
4) Antiretroviral treatment-naive, as defined by:
a) No prior treatment with ATV or RAL or TDF/FTC or 3TC either for treatment or
prophylaxis.
b) No antiretroviral therapy with drugs = 1 week (excluding ATV or RAL or
TDF/FTC or 3TC; see above)
However, in specific settings of antiretroviral treatment including: post exposure
prophylaxis (PEP), pre-exposure prophylaxis (PREP) and/or HAART exposure
for reduction of risk of mother-to-child transmission, the following prior
antiretroviral exposure exceptions will apply, allowing the subject entry into the
study:
i) < 6 weeks of triple antiretroviral therapy (3 drugs of any class, except ATV or
integrase inhibitors or TDF/FTC or 3TC)
or
ii) < 4 weeks of dual antiretroviral therapy (2 drugs of any class, except ATV or
integrase inhibitors or TDF/FTC or 3TC)
or
iii) < 1 week of mono-antiretroviral therapy (1 drug of any class, except ATV or
integrase inhibitors or TDF/FTC or 3TC)
5) Medically stable to participate in the study, in the opinion of the investigator, and as determined by medical history, physical examination, and clinical laboratory
evaluations.
Age and Sex
6) Men and women, = age 18 (or minimum age as determined by local regulatory or as legal requirements dictate)
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. Since acceptable and available methods of contraception vary among
different countries, participating women may choose their preferred contraceptive
method based on physician recommendations.
WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
• Amenorrhea = 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement therapy
(HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL.
Women who are using oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical products
such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides)
to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
Are the trial subjects under 18? no
Number of subjects for this age ra
Sex and Reproductive Status
1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 8 weeks after the last dose of
investigational product.
2) WOCBP using a prohibited contraceptive method. Caution is warranted with
co-administration of oral contraceptives (ethinyl estradiol and norethindrone); see
Protocol Appendix 4.
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
Target Disease Exceptions
5) Screening HIV Genotype showing resistance to any component of the study regimen, as described in Protocol Appendix 3;
6) Any antiretroviral therapy within 30 days prior to screening;
7) Presence of a newly diagnosed HIV-related opportunistic infection or any medical
condition requiring acute therapy at the time of enrollment; Suspected primary (acute) HIV infection;
Medical History and Concurrent Diseases
8) Co-infection with human hepatitis B virus (HBV), hepatitis C virus (HCV). HBV
coinfection is defined by HBsAg positive or anti- HBc positive; HCV coinfection is
defined as HCV Ab positive plus detectable HCV RNA.
9) History of or current presence of cardiac disease, defined by presence of arrhythmias, ischemic disease, or a conduction abnormality including left bundle branch block (LBB) or left anterior fascicular block (LAFB), > 1st degree atrioventricular block (AVB), 2nd/3rd degree AVB, or any cardiac abnormality deemed clinically significant by investigator. In addition, the following ECG findings are exclusionary:
a) PR Interval > 260msec (severe first degree AV block)
b) QRS Interval > 120msec
10) Gastro-esophageal reflux disease (GERD), or conditions that would lead the
investigator to believe that there is a significant likelihood that the subject will need
prohibited therapies or medications (eg, Proton Pump Inhibitors) while on study
therapy;
11) Active alcohol or substance use sufficient, in the investigator’s opinion, to prevent
adequate compliance with study therapy or to increase the risk of developing
pancreatitis or chemical hepatitis;
Physical and Laboratory Test Findings
12) Liver enzymes (ALT/AST) > 5 times the upper limit of normal
13) Alkaline phosphatase > 5 times the upper limit of normal
14) Serum creatinine > 1.5 times the upper limit of normal
15) Creatinine clearance < 60 cc/min
16) Bilirubin >1.5 times the upper limit of normal
17) Hemoglobin < 8.0 g/dL
18) Platelets < 50,000 cells/mm3
19) Urine protein = 2+
Prohibited Treatments and/or Therapies
20) Refer to Appendix 4, which details prohibited and cautionary therapies.
Other Exclusion Criteria
21) Prisoners or subjects who are involuntarily incarcerated
22) Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method