Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication REYATAZ ® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and in pediatric patients 3 months and older weighing at least 5 kg. Limitations of Use: • REYATAZ is not recommended for use in pediatric patients below the age of 3 months due to the risk of kernicterus [see Use in Specific Populations (8.4) ] . FDA label
Also known as Atazanavir (current formulation), Atazanavir powder, Atazanavir (immediate switch), BMS-232632, Reyataz, ATV
Atazanavir · 24 trials · 8 indications
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
ALT=alanine aminotransferase; SGPT=serum glutamic-pyruvic transaminase; AST=aspartate aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; ULN=upper limit of normal. Grading by the National Institute of Health Division of AIDs and World Health Organization criteria. Hemoglobin (g/dL): Grade (Gr)1=9.5-11.0; Gr 2=8.0-9.4; Gr 3=6.5-7.9; Gr 4=\<6.5. Neutrophils, absolute (/mm\^3): Gr 1=\>=1000-\<1500; Gr 2= \>=750-\<1000; Gr 3=\>=500-\<750; Gr 4=\<500. ALT/SGPT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. AST/SGOT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. Alkaline phosphatase(\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5: Gr 3=5.1-10; Gr 4=\>10. Total bilirubin (\*ULN): Gr 1=1.1-1; Gr 2=1.6-2.5; Gr 3=2.6-5; Gr 4=\>5. Amylase (\*ULN): Gr 1=1.10-39; Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Lipase (\*ULN): Gr 1=1.10-1.39: Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12.0; Gr 3=12.1-15.0; Gr 4=\>15.
Electrocardiogram parameters were measured at baseline for QTC Bazett, QTC Fridericia, and PR interval. The mean change from baseline at week 48 is reported by arm in milliseconds.
CDC Class C events are AIDS-defining events that include recurrent bacterial pneumonia (\>=2 episodes in 12 months); candidiasis of the bronchi, trachea, lungs, or esophagus; invasive cervical carcinoma; disseminated or extrapulmonary coccidioidomycosis; extrapulmonary cryptococcosis; chronic intestinal cryptosporidiosis (\>1 month); cytomegalovirus disease; HIV-related encephalopathy; herpes simplex: chronic ulcers, or bronchitis, pneumonitis, or esophagitis; disseminated or extrapulmonary histoplasmosis; chronic intestinal isosporiasis; Kaposi sarcoma; immunoblastic or primary brain Burkitt lymphoma; mycobacterium avium complex, kansasii, or tuberculosis; mycobacterium, other species; Pneumocystis carinii pneumonia; progressive multifocal leukoencephalopathy; Salmonella septicemia; recurrent toxoplasmosis of brain; HIV wasting syndrome (involuntary weight loss \>10% of baseline body weight) with chronic diarrhea or chronic weakness and documented fever for ≥1 month.
Treatment Failure through Week 48 defined as virologic rebound (HIV RNA \>=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) \>= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA \>=400 c/mL followed by discontinuation of study therapy.
Brachial artery reactivity assessed by noninvasively measuring brachial artery diameter and flow velocities in response to overinflated blood pressure cuff (Flow mediated dilation (FMD))in subjects switching to atazanavir and in subjects continuing on a stable antiretroviral regimen
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AIDS Defining Diagnosis ( CDC Class C AIDS Events) are identified from HIV Related Diagnosis.
The proportion of patients with undetectable HIV RNA viral load ( \< 50 copies/ml) at week 24.
Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Cmax was derived from plasma concentration versus time data.
Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. AUC(0-T) and AUC(INF) were derived from plasma concentration versus time data.
Tasting atazanavir (15 mg, administered as a 5 mL oral suspension) was defined as taking the sample into the mouth, swishing it across the tongue for approximately 30 seconds without swallowing, and then spitting it out. Immediately after tasting each treatment, participants scored the treatments for sweetness using a subjective sweet intensity scoring system: 0=not sweet, 1=mildly sweet, 2=moderately sweet, 3=very sweet. Participants were permitted to select a whole or half score number (for example, 1.5) between the minimum score of 0 and the maximum score of 3.0. The higher the score, the greater the sweetness.
Tasting atazanavir (15 mg, administered as a 5 mL oral suspension) was defined as taking the sample into the mouth, swishing it across the tongue for approximately 30 seconds without swallowing, and then spitting it out. Immediately after tasting each treatment, participants scored the treatments for sweetness using a subjective sweet intensity scoring system: 0=not sweet, 1=mildly sweet, 2=moderately sweet, 3=very sweet. Participants were permitted to select a whole or half score number (for example, 1.5) between the minimum score of 0 and the maximum score of 3.0. The higher the score, the greater the sweetness.
EM participants are those with functional CYP2C19 alleles.
EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Tmax=time to maximum concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Cmax=maximum observed plasma concentration; Cmin=minimum observed plasma concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
AUC(TAU)=area under the plasma concentration-time curve in 1 dosing interval; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Cmax = maximum observed plasma concentration of atazanavir at specified time points.
Cmax = maximum observed plasma concentration of ritonavir at specified time points.
AUC = area under the concentration curve (AUC \[TAU\]) of atazanavir in one dosing interval from time zero to 24 hours.
AUC = area under the concentration curve (AUC \[TAU\]) of ritonavir in one dosing interval.
Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.
Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.
T 1/2 = terminal elimination half life of atazanavir at specified time points.
T 1/2 = terminal elimination half life of ritonavir at specified time points.
Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.
Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.
| Arm | Type | Description |
|---|---|---|
| Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg | EXPERIMENTAL | Patients weighing 5 to \<10 kg received atazanavir (ATV), 150-mg powder dosed in 50-mg packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by patient's weight on the day of first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage. All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. |
| Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg | EXPERIMENTAL | Patients weighing 10 to \<15 kg received ATV powder, 200 mg, dosed in 50-mg sachet packets and RTV oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. |
| Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg | EXPERIMENTAL | Patients weighing 15 to \<25 kg received 250 mg of ATV powder dosed in 50-mg sachet packets, with 80 mg of RTV solution. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from powder to the capsule formulation of ATV. Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. |
| A1 | EXPERIMENTAL | - |
| A | EXPERIMENTAL | ARM A: Switch current PI to atazanavir 400 mg once daily plus current \> 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 24 weeks. Subjects currently on ritonavir (RTV) (400 mg BID or greater) or RTV-boosted PI (\<400 mg/day) , or tenofovir (TDF) as backbone NRTI therapy, will switch to ATV 300 mg boosted with RTV 100mg once daily. |
| B | ACTIVE_COMPARATOR | ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus \> 2 NRTIs) for 24 weeks |
| G1 | ACTIVE_COMPARATOR | - |
| G2 | ACTIVE_COMPARATOR | - |
| 1 | ACTIVE_COMPARATOR | - |
| 2 | ACTIVE_COMPARATOR | - |
| Atazanavir | EXPERIMENTAL | - |
| Atazanavir/Ritonavir | EXPERIMENTAL | - |
| Lopinavir/Ritonavir | ACTIVE_COMPARATOR | Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). |
| I | ACTIVE_COMPARATOR | ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
| II | ACTIVE_COMPARATOR | ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
| III | ACTIVE_COMPARATOR | LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
| Open label single arm | EXPERIMENTAL | Introduction of treatment regimen with atazanavir 300mg qd + ritonavir 100mg qd + dolutegravir 50mg qd |
| Atazanavir and Cobicistat | OTHER | Stage 1:Taste evaluation using Active Pharmaceutical Ingredient (API) Stage 2:Taste Optimization using API (flavours and sweeteners) Stage 3:Prototypes of the API - containing clinical trial materials |
| Treatment A: Atazanavir + Cobicistat coadministered | EXPERIMENTAL | Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, following a light meal on Day 1 or 8 |
| Treatment B: Atazanavir/Cobicistat FDC | EXPERIMENTAL | Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8 |
| Treatment C: Atazanavir + Cobicistat coadministered | EXPERIMENTAL | Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day 15 or 22 |
| Treatment D: Atazanavir/Cobicistat FDC | EXPERIMENTAL | Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22 |
| Treatment E: Atazanavir/Cobicistat FDC | EXPERIMENTAL | Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29 |
| Atazanavir + 10% aspartame | ACTIVE_COMPARATOR | - |
| Atazanavir + 4.2% aspartame | ACTIVE_COMPARATOR | - |
| Atazanavir + 4.2% aspartame and sucralose | ACTIVE_COMPARATOR | - |
| Voriconazole, 200 mg BID (EM) | ACTIVE_COMPARATOR | - |
| Atazanavir/Ritonavir, 300/100 QD (EM & PM) | ACTIVE_COMPARATOR | - |
| Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM) | ACTIVE_COMPARATOR | - |
| Voriconazole, 50 mg BID (PM) | ACTIVE_COMPARATOR | - |
| Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM) | ACTIVE_COMPARATOR | - |
| 3 | ACTIVE_COMPARATOR | - |
| A2 | ACTIVE_COMPARATOR | - |
| A3 I | EXPERIMENTAL | - |
| A3 II | EXPERIMENTAL | - |
| B1 | ACTIVE_COMPARATOR | - |
| B2 | ACTIVE_COMPARATOR | - |
| B3 I | EXPERIMENTAL | - |
| B3 II | EXPERIMENTAL | - |
| Treatment | EXPERIMENTAL | - |
| C | EXPERIMENTAL | - |
| D | EXPERIMENTAL | - |
| E | EXPERIMENTAL | - |
| A3 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Atazanavir powder | DRUG | Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation. |
| Ritonavir oral solution | DRUG | Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation. |
| Atazanavir capsules | DRUG | Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. |
| Ritonavir capsules | DRUG | Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight. |
| Atazanavir + Ritonavir | DRUG | Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks |
| Atazanavir | DRUG | atazanavir 400 mg once daily |
| current antiretroviral regimen | DRUG | Continue current antiretroviral regimen for 24 weeks, single or RTV-boosted PI plus \> 2 NRTIs |
| Atazanavir+ritonavir | DRUG | Capsules, Oral, 300mg/100mg, once daily, 24 weeks. |
| Lopinavir+ritonavir | DRUG | Capsules, Oral, 800mg/200mg, twice daily, 24 weeks. |
| atazanavir/ritonavir +2 NRTIs (immediate Switch Group) | DRUG | Capsules, Oral, ATV 300mg/RTV 100mg + 2 NRTIs, QD, 48 weeks. |
| LPV/r +2 NRTIs (Delayed/optional Switch Group) | DRUG | Capsules, Oral, LPV 400mg/RTV 100mg +2 NRTIs, BID, 24 weeks then option to switch to ATV arm or stay until 48 weeks. |
| Atazanavir (immediate switch) | DRUG | Capsules, Oral, 400mg, Once daily, 48 weeks. |
| Atazanavir (Week 24 switch) | DRUG | Capsules, Oral, 400mg, Once daily, 48 weeks. |
| Atazanavir/Ritonavir | DRUG | Tablets, Oral, 300/100 mg, once daily, indefinitely |
| Tenofovir/Emtricitabine | DRUG | Tablets, Oral, 300/200 mg, once daily, indefinitely |
| Lopinavir/ritonavir | DRUG | Tablets, Oral, 400/100 mg, twice daily, indefinitely |
| Atazanavir + ritonavir + tenofovir + nucleoside | DRUG | Active Comparator, Capsules, tablets, Oral |
| Atazanavir + saquinavir + tenofovir + nucleoside | DRUG | Active Comparator, Capsules, tablets, Oral |
| Lopinavir/ritonavir + tenofovir + nucleoside | DRUG | Active Comparator, Capsules, tablets, Oral |
| Lamivudine/Zidovudine | DRUG | - |
| Efavirenz | DRUG | - |
| atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg | DRUG | Switch to single arm treatment atazanavir-ritonavir 300-100 mg + dolutegravir 50 mg therapy for 24 weeks |
| Ritonavir | DRUG | - |
| Saquinavir | DRUG | - |
| Nelfinavir mesylate | DRUG | - |
| Stavudine | DRUG | - |
| Didanosine | DRUG | - |
| Cobicistat | DRUG | - |
| Active Pharmaceutical Ingredient | DRUG | - |
| Atazanavir/Cobicistat FDC | DRUG | Atazanavir 300-mg/cobicistat 150-mg FDC tablet |
| Atazanavir (current formulation) | DRUG | Solution, oral, atazanavir 15 mg/5 mL with 10% aspartame, single dose |
| Atazanavir, powder for oral use 1 (POU1) | DRUG | Solution, oral, atazanavir 15 mg/5 mL with 4.2% aspartame, single dose |
| Atazanavir (POU2) | DRUG | Solution, oral, atazanavir 15 mg/5 mL with 4.2% aspartame and sucralose, single dose |
| Voriconazole | DRUG | Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. |
| Raltegravir | DRUG | Tablet, Oral, 400 mg, twice daily for 5 Days |
| Atazanavir + Raltegravir | DRUG | Capsule/Tablet, Oral, 300/400, twice daily for 14 Days |
| Atazanavir/Ritonavir+Omeprazole | DRUG | Capsules/capsules + Capsules, Oral, 300/100 mg + 20 mg, once daily in PM + once daily in AM, 7 days. |
| Atazanavir + Ritonavir + Combivir | DRUG | Capsules, tablets, Oral, initially ATV 300 mg + RTV 100 mg + ZDV/3TC 300/150 mg, dose escalated to ATV 400 mg + RTV 100 mg + ZDV/3TC 300/150 mg, ATV and RTV once daily, lamivudine (ZDV) / zidovudine (3TC) twice daily (BID), up to 36 weeks |
| Atazanavir+Ritonavir+Tenofovir | DRUG | Cap/Cap/Tablet, Oral, 300/100/300 mg, QAM/QAM/QAM, 10 days. |
| Atazanavir+Ritonavir+Tenofovir+Famotidine | DRUG | Cap/Cap/Tablet/Tablet, Oral, 300/100/300/20 mg, QAM/QAM/QAM/Q12 coadmin, 7 days. |
| Nevirapine | DRUG | Tablets, Oral, 200 mg, Twice daily, 3 days. |
| Nevirapine + Atazanavir/Ritonavir | DRUG | Tablets + Capsules/Capsules, Oral, 200 mg + 300/100 mg, twice daily + once daily, 10 days. |
| Atazanavir/Ritonavir/Lopinavir/ritonavir | DRUG | - |
Key Inclusion Criteria: * Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by: * HIV DNA polymerase chain reaction * HIV RNA with values ≥1,000 copies/mL * Positive HIV enzyme-linked immunosorbent assay at ≥18 mont...
Atazanavir is an antiretroviral medicine used to treat HIV and HIV-1 infection in adults. It is studied as part of combination regimens for human immunodeficiency virus infections, including nucleoside sparing regimens in patients with detectable viremia. Bristol-Myers Squibb Company develops it under the ticker BMY.
Atazanavir is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company has sponsored Phase 1, Phase 2, and Phase 3 studies of the drug in HIV and HIV-1 infection, including bioequivalence and taste assessment studies of different atazanavir formulations.
Atazanavir is in Phase 3 development for HIV and HIV-1 infection. It is an investigational small molecule, and the clinical program includes 17 trials, of which 16 are completed and none are currently active. Studies have enrolled 1,399 participants in randomized, double-blind, active-controlled designs.
Atazanavir has been studied in trials including NCT02542852, a Phase 2 nucleoside sparing regimen study in HIV-1 infected patients with detectable viremia, and NCT01837719, a Phase 1 bioequivalence study of atazanavir and cobicistat. Phase 1 taste studies include NCT02307656 and NCT01404572.