Open- Label Randomized Study Comparing Efficacy and Safety of ATV/RTV+3TC with ATV/RTV+TDF/FTC in HIV- Infected, Treatment Naïve Subjects, Followed by Treatment with ATV/RTV+3TC
- Conditions
- HIVMedDRA version: 14.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2011-006187-47-DK
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
1) Signed Written Informed Consent
a) 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.
b) A freely given PK sub-study consent form must be obtained from the subset of
subjects participating in the intensive PK sub-study.
2) Target Population
a) Treatment-naive HIV-1-infected subjects (< 48 hours of any ARV is allowed)
b) Subjects who have an HIV-1 RNA level = 1000 c/mL at screening
c) Subjects who have a CD4+ cell count > 100 cells/mm3.
3) Age and Reproductive Status
a) Men and women, 18 years of age or older (or minimum age as determined by local regulatory or legal requirements)
b) Women of childbearing potential (WOCBP) must use method(s) of contraception based on the tables in Appendix 2. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception should be determined in consultation with the investigator. WOCBP must follow instructions for birth control for a period of 30 days after the last dose of investigational product.
c) Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
d) Women must not be breastfeeding
e) Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men that are sexually active with WOCBP must follow instructions for birth control for a period of 90 days aftert the last dose of investigational product.
f) Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile--see Section 3.3.3 for the definition of WOCBP) and azoospermic men do not require contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1) Target Disease Exceptions
a) Subjects who have an HIV-1 RNA level = 500,000 c/mL at screening
b) Screening HIV genotype showing resistance to any component of the study regimen (ATV, RTV, 3TC, TDF/FTC) or primary resistance mutations to HIV protease inhibitors (see Appendix 4)
c) Previously documented HIV-2 infection
2) Medical History and Concurrent Diseases
a) Acute or chronic hepatitis B virus (HBV)
b) Acute hepatitis C virus (HCV) co-infection.
Note: Chronic co-infection with hepatitis C is not an exclusion criteria. Subjects with acute hepatitis C may have the option to be screened after the event has evolved into a chronic infection.
c) Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment. Subjects on stable maintenance therapy for an opportunistic infection may be enrolled
d) Primary HIV infection
e) History or current 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), 2nd- or 3rd-degree atrioventricular block (AVB), or any cardiac abnormality deemed clinically significant by the investigator. In addition, the following ECG findings are exclusionary:
i) PR Interval > 260 msec (severe 1st degree AV Block)
ii) QRS Interval > 120 msec
f) Moderate-to-severe hepatic insufficiency
g) Obstructive liver disease
h) Recent therapy with agents having significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment, or therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect CYP3A4
i) Concomitant administration of a proton pump inhibitor (PPI) or H2 blocker or any other drug with potential interaction with the investigational productsj) Life expectancy < 1 year according to the judgment of the investigator
k) 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
l) History or ongoing psychiatry disorder
3) Physical and Laboratory Test Findings
a) Screening laboratory analysis showing any of the following abnormal laboratory
results:
i) Grade IV glucose
ii) Grade IV electrolytes
iii) Grade IV transaminases
iv) Grade IV hematology
v) Calculated creatinine clearance < 60 mL/min as estimated by the Cockcroft- Gault equation.
4) Allergies and Adverse Drug Reaction
a) Hypersensitivity to any component of the study drug formulations.
5) Sex and Reproductive Status
a) Women with a positive pregnancy test on enrollment or prior to study drug administration
6) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness (eg, infectious disease)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the response rate (proportion of subjects with HIV-1 RNA < 40 c/mL) at Week 48 of a QD regimen of ATV/RTVHS 300/100 mg combined with either one additional drug (3TC 300 mg QD) or two additional drugs (TDF/FTC 300/200 mg QD).;Secondary Objective: To assess efficacy by determining:<br>- The proportion of subjects with HIV-1 RNA < 40 c/mL at Week 96.<br>- The proportion of subjects with HIV-1 RNA < 400 c/mL at Weeks 48 and 96.<br>• To assess safety, as measured by:<br>- Incidence of SAEs and AEs leading to discontinuation through Weeks 48 and 96.<br>- Changes from baseline in renal function [using estimated glomerular filtration rate (eGFR)] and BMD at Weeks 48 and 96.<br>• To assess the incidence of newly emergent genotypic substitutions and phenotypic resistance to study drugs among subjects with virologic failure through Weeks 48 and 96.;Primary end point(s): Proportion of subjects with HIV-1 RNA < 40 c/mL at Week 48;Timepoint(s) of evaluation of this end point: Week 48
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Proportion of subjects with HIV-1 RNA < 400 c/mL at Week 48, and proportion of subjects with HIV-1 RNA < 40 c/mL and < 400 c/mL at Week 96.<br>• Incidence rates of SAEs and AEs leading to discontinuation through Weeks 48 and 96; percent change from baseline in eGFR and bone mineral density at Weeks 48 and 96.<br>• Incidence rates of newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failures through Week 48 and 96.;Timepoint(s) of evaluation of this end point: Week 48 and 96