HIV
Conditions
Brief summary
The primary objective of this study in antiretroviral (ARV)-naïve Human immunodeficiency virus 1 (HIV-1) ribonucleic acid infected subjects is to compare the response rate at Week 48 of a daily regimen of Atazanavir (ATV)/ Ritonavir (RTV)HS 300/100 mg combined with either one additional drug \[Lamivudine (3TC) 300 mg daily\] or 2 additional drugs \[Tenofovir/Emtricitabine(TDF/FTC) 300/200 mg daily\].
Interventions
DRUGAtazanavir
Capsule, oral, 300 mg, Once daily (QD), 96 weeks
DRUGRitonavir
Tablets, oral, 100 mg, QD, 96 Weeks
DRUGLamivudine
Tablet, oral, 300 mg, QD, 96 Weeks
Tablets, oral, 300/200 mg, QD, 48 Weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Signed Written Informed Consent. i) 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. ii) A freely given Pharmacokinetics (PK) sub-study consent form must be obtained from the subset of subjects participating in the intensive PK sub-study. \- Target Population. i) Treatment-naive HIV-1-infected subjects (\< 48 hours of any ARV is allowed). ii) Subjects who have an HIV-1 Ribonucleic acid (RNA) level ≥ 1000 c/mL at screening. iii) Subjects who have a Antigenic marker of helper/inducer T lymphocytes (CD4) + cell count \> 100 cells/mm3. \- Age and Reproductive Status. i) Men and women, 18 years of age or older (or minimum age as determined by local regulatory or legal requirements). ii) Women of childbearing potential (WOCBP) must use highly effective methods of birth control for up to 8 weeks after the last dose of investigational product to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 30 days after dosing has been completed. iii) Acceptable methods of highly effective birth control include:. A. Condom with spermicide. B. Diaphragm and spermicide. C. Cervical cap and spermicide \- Since acceptable and available methods of contraception vary among different countries, participating women may choose their preferred contraceptive method atazanavir AI424494 BMS-232632 Clinical Protocol Date: 31-01-2012 33 based on physician recommendations. Caution is warranted with co-administration of oral contraceptives (ethinyl estradiol and norethindrone). i) Women must have a negative serum or urine pregnancy test \[minimum sensitivity 25 IU/L or equivalent units of Human chorionic gonadotropin (HCG)\] within 24 hours prior to the start of investigational product. ii) Women must not be breastfeeding. iii) Sexually active fertile men must use highly effective birth control if their partners are WOCBP.
Exclusion criteria
\- Target Disease Exceptions. i) Subjects who have an HIV-1 RNA level ≥500,000 c/mL at screening. ii) Screening HIV genotype showing resistance to any component of the study regimen (ATV, RTV, 3TC, TDF/FTC). iii) Previously documented HIV-2 infection. \- Medical History and Concurrent Diseases. i) Acute or chronic hepatitis B virus (HBV) or Acute hepatitis C virus (HCV) co-infection. \- Note Chronic co-infection with hepatitis C is not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With HIV-1 RNA < 40 c/mL at Week 48 | Week 48 | Proportion of subjects with HIV-1 RNA \< 40 c/mL at Week 48. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With HIV-1 RNA < 400 c/mL at Week 48 | Week 48 | Proportion of Participants with HIV-1 RNA \< 400 c/mL at Week 48. |
| Proportion of Participants With HIV-1 RNA < 40 c/mL and < 400 c/mL at Week 96 | Week 96 | proportion of subjects with HIV-1 RNA \< 40 c/mL and \< 400 c/mL at Week 96. |
| Incidence of Adverse Events Through Weeks 48 and 96 | through weeks 48 and 96 | Incidence of Adverse Events through weeks 48 and 96 including serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation. There were no SAEs or AEs reported in this early terminated study. |
| Percent Change From Baseline in eGFR and Bone Mineral Density at Weeks 48 and 96 | Weeks 48 and 96 | Percent change from baseline in eGFR and bone mineral density at weeks 48 and 96. |
| Incidence of Newly Emergent Genotypic Substitutions and Phenotypic Resistance to Study Drugs for Virologic Failures Through Week 48 and 96 | Through week 48 and 96 | Incidence of newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failures through Week 48 and 96. |
Participant flow
Pre-assignment details
3 randomized and treated
Participants by arm
| Arm | Count |
|---|---|
| Arm A Reference Therapy: Atazanavir, heat-stable ritonavir \[ATV/RTVHS\] 300/100 mg QD + Tenofovir/emtricitabine \[TDF/FTC\] 300/200 mg QD by mouth for 48 weeks | 2 |
| Arm B Experimental Therapy: Atazanavir, heat-stable ritonavir \[ATV/RTVHS\] 300/100 mg QD + Lamivudine \[3TC\] 300 mg QD by mouth for 48 weeks | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early termination of Study | 2 | 1 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Proportion of Participants With HIV-1 RNA < 40 c/mL at Week 48
Proportion of subjects with HIV-1 RNA \< 40 c/mL at Week 48.
Time frame: Week 48
Population: Week 48 not reached for any participant, data not collected at week 48
Secondary
Incidence of Adverse Events Through Weeks 48 and 96
Incidence of Adverse Events through weeks 48 and 96 including serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation. There were no SAEs or AEs reported in this early terminated study.
Time frame: through weeks 48 and 96
Population: Week 48 and 96 not reached for any participant, data not collected through week 48 and 96
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Incidence of Adverse Events Through Weeks 48 and 96 | Serious Adverse Events (SAEs) | — |
| Unknown | Incidence of Adverse Events Through Weeks 48 and 96 | Adverse Events (AEs) leading to discontinuation | — |
Secondary
Incidence of Newly Emergent Genotypic Substitutions and Phenotypic Resistance to Study Drugs for Virologic Failures Through Week 48 and 96
Incidence of newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failures through Week 48 and 96.
Time frame: Through week 48 and 96
Population: Week 48 and 96 not reached for any participant, data not collected through week 48 and 96
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Incidence of Newly Emergent Genotypic Substitutions and Phenotypic Resistance to Study Drugs for Virologic Failures Through Week 48 and 96 | Newly Emergent Genotypic Substitutions | — |
| Unknown | Incidence of Newly Emergent Genotypic Substitutions and Phenotypic Resistance to Study Drugs for Virologic Failures Through Week 48 and 96 | Phenotypic Resistance | — |
Secondary
Percent Change From Baseline in eGFR and Bone Mineral Density at Weeks 48 and 96
Percent change from baseline in eGFR and bone mineral density at weeks 48 and 96.
Time frame: Weeks 48 and 96
Population: Week 48 and 96 not reached for any participant, data not collected at week 48 and 96
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Percent Change From Baseline in eGFR and Bone Mineral Density at Weeks 48 and 96 | eGFR | — |
| Unknown | Percent Change From Baseline in eGFR and Bone Mineral Density at Weeks 48 and 96 | Bone Mineral Density | — |
Secondary
Proportion of Participants With HIV-1 RNA < 400 c/mL at Week 48
Proportion of Participants with HIV-1 RNA \< 400 c/mL at Week 48.
Time frame: Week 48
Population: Week 48 not reached for any participant, data not collected at week 48
Secondary
Proportion of Participants With HIV-1 RNA < 40 c/mL and < 400 c/mL at Week 96
proportion of subjects with HIV-1 RNA \< 40 c/mL and \< 400 c/mL at Week 96.
Time frame: Week 96
Population: Week 48 not reached for any participant, data not collected at week 96
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Proportion of Participants With HIV-1 RNA < 40 c/mL and < 400 c/mL at Week 96 | HIV-1 RNA < 40 c/mL | — |
| Unknown | Proportion of Participants With HIV-1 RNA < 40 c/mL and < 400 c/mL at Week 96 | HIV-1 RNA < 400 c/mL | — |