HIV, COMBINATION THERAPY MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection
Conditions
Interventions
Trade Name: Reyataz
Product Name: Reyataz
Product Code: BMS-232632
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: atazanavir
CAS Number: 229975-97-7
Current Sponsor code: BMS-232632
Other des
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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) 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
Exclusion criteria
Exclusion criteria: 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): * Primary: Proportion of subjects with HIV RNA < 50 c/mL at Week 24. * Secondary: 1) Proportion of subjects with non-response at Week 8. 2) Proportions of subjects with HIV RNA < 50 c/mL at Weeks 48 and 96. 3) Proportions of subjects with HIV RNA < 400 c/mL at Weeks 24, 48 and 96. 4) Antiretroviral activity at Weeks 24, 48, and 96: - Change from baseline in CD4 cell counts - Emergence of genotypic substitutions and phenotypic resistance among subjects with virologic failure (HIV RNA = 400 c/mL) 5) Safety through Weeks 24, 48, and 96 as measured by: - Frequency of adverse events, SAEs, discontinuations, death, and laboratory abnormalities. - Changes from baseline in select laboratory tests (total bilirubin, fasting lipids). - QRS widening, QT and PR prolongation from ECGs 6) Assessment of Pharmacokinetics (Trough PK for all subjects at selected visits through Week 48; Intensive PK for 16 subjects in Group 1 at Week 2): - To estimate the inhibitory quotient for ATV of each subject in Group 1, and for boosted ATV in Group 2, based on trough concentration and estimated protein-binding corrected EC90 at baseline. - To explore correlations between trough concentrations of ATV and RAL (Group 1) and boosted ATV (Group 2) over time with efficacy and safety parameters. - To characterize the PK profile of ATV and RAL co-administered in Group 1 (AUC, Cmin, Cmax). - To estimate the ATV PK when ATV is co-administered with RAL BID (Group 1) relative to when it is co-administered with RTV + TDF/FTC QD (historical control).;Main Objective: The primary objective of this study is to determine the proportion of subjects with HIV RNA < 50 c/mL at Week 24 in HIV-1 infected Treatment-Naive Subjects.;Secondary Objective: Determine: 1) proportion of subjects with non-response at Week (WK) 8 2) proportions of subjects with HIV RNA<50 c/mL at WK 48 & 96 3) proportions of subjects with HIV RNA<400 c/mL at WK 24, 48 & 96 4) antiretroviral activity at WK 24, 48 & 96 as mea | — |
Countries
France
Outcome results
None listed