Phase IIB Pilot of Atazanavir + Raltegravir
- Conditions
- HIV
- Interventions
- Registration Number
- NCT00768989
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine if the combination of atazanavir and raltegravir taken together is safe and effective in the treatment of human immunodeficiency virus (HIV).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 167
-
Human Immunodeficiency Virus (HIV)-1 positive status
-
HIV ribonucleic acid (RNA) level >=5000 copies/mL
-
Antiretroviral treatment-naive
-
Absolute Cluster of Differentiation 4 (CD4) cell count meeting 1 of the following criteria:
-
<350 cells/mm^3
-
Screening CD4 >=350 and <=500 cells/mm^3 ONLY if at least 1 of the following conditions apply:
- Screening HIV RNA level >100,000 copies/mL, or
- CD4 decline >50-100 cells/mm^3/year, or
- Age >=55 years
-
Any CD4 cell count, if participant has a history of an acquired immune deficiency syndrome-defining illness
-
Medically stable
- Screening HIV genotype showing resistance to any component of the study regimen (Atazanavir, Raltegravir, Tenofovir/Emtricitabine)
- Hepatitis B or hepatitis C coinfection
- History of or current cardiac disease
- Electrocardiogram findings:
- PR Interval >260 msec (severe 1st degree atrioventricular block)
- QRS Interval >120 msec
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atazanavir + Raltegravir Atazanavir Atazanavir 300 mg twice daily + Raltegravir 400 mg twice daily Atazanavir + Raltegravir Raltegravir Atazanavir 300 mg twice daily + Raltegravir 400 mg twice daily Atazanavir + Ritonavir + Tenofovir /Emtricitabine Atazanavir Atazanavir, 300 mg once daily, + Ritonavir, 100 mg once daily, + Tenofovir 300 mg/Emtricitabine, 200 mg once daily Atazanavir + Ritonavir + Tenofovir /Emtricitabine Ritonavir Atazanavir, 300 mg once daily, + Ritonavir, 100 mg once daily, + Tenofovir 300 mg/Emtricitabine, 200 mg once daily Atazanavir + Ritonavir + Tenofovir /Emtricitabine Tenofovir/Emtricitabine Atazanavir, 300 mg once daily, + Ritonavir, 100 mg once daily, + Tenofovir 300 mg/Emtricitabine, 200 mg once daily
- Primary Outcome Measures
Name Time Method Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 At Week 24 from Baseline The number of HIV 1-infected treatment-naive participants with an HIV RNA level \<50 copies/mL after 24 weeks of treatment. Confirmed virologic response noncompleter=failure (NC=F); noncompleter=missing (NC=M); virologic response-observed cases (VR-OC).
- Secondary Outcome Measures
Name Time Method Number of Nonresponders at Week 8 At Week 8 from Baseline Participants were classified as nonresponders if they had an HIV RNA level ≥400 copies/mL and a decrease from baseline \<2 log10 copies/mL.
Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96 At Weeks 48 and 96 from Baseline Participant HIV RNA level was determined at Weeks 48 and 96 using the Roche Amplicor® Ultrasensitive Assay Version 1. VR-OC=Virologic response-observed cases.
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 At Week 24 from Baseline NC=F: noncompleter=failure; NC=M: noncompleter=missing; VR-OC: virologic response-observed
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48 At Week 48 from Baseline Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96 At Week 96 from Baseline Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24 Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation Week 1 to Week 96, continuously AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in drug dependency or drug abuse, or is an important medical event.
Baseline and Mean Change From Baseline in Total Cholesterol Levels From Baseline to Week 24 and Week 48 The mean change from baseline in participant fasting lipids was determined using fasting serum samples.
Mean Change From Baseline in Total Bilirubin Level From Baseline to Week 24 and Week 48 Mean Change From Baseline in Electrocardiogram Findings From Baseline to Week 24 The incidence of QRS wave widening and QT and PR prolongation on participant electrocardiogram findings were evaluated at study Week 24.
Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval At Week 2 from Baseline Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Raltegravir Cmax in 1 Dosing Interval At Week 2 from Baseline Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Atazanavir Time of Maximum Observed Plasma Concentration (Tmax) At Week 2 from Baseline Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Raltegravir Tmax At Week 2 from Baseline Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose At Week 2 from Baseline Raltegravir Cmin 12 Hours Postdose At Week 2 from Baseline Atazanavir Cmin Prior to the Morning Dose At Week 2 from Baseline Raltegravir Cmin Prior to the Morning Dose At Week 2 from Baseline Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval At Week 2 from Baseline Raltegravir AUC (0-12h) in 1 Dosing Interval At Week 2 from Baseline Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval At Week 2 from Baseline AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2.
Atazanavir Individual Inhibitory Quotient (IQ) At Week 2 from Baseline Individual IQ was defined at Cmin at Week 2 divided by the protein binding adjusted EC90 (ie, the drug concentration observed to inhibit virion production by 90% in a cell-based assay) values for Atazanavir that were derived from individual participant clinical isolates.
Atazanavir Terminal Elimination Half Life At Week 2 from Baseline Raltegravir Terminal Elimination Half Life At Week 2 from Baseline Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants While on treatment from Baseline through Week 96 ULN=upper limit of normal. Hematocrit(%) Grade (Gr) 1: ≥28.5-\<31; Gr 2: ≥24-\<28.5; Gr 3: ≥19.5-\<24; Gr 4: \<19.5. Hemoglobin (g/dL) Gr 1: 9.5-11; Gr 2: 8-9.4; Gr 3: 6.5-7.9; Gr 4: \<6.5. Platelets (/mm\^3) Gr 1: 75,000-99,000; Gr 2: 50,000-74,999; Gr 3: 20,000-49,999; Gr 4: \<20,000. White Blood Cells (/mm\^3) Gr 1: \>2500-4000; Gr 2: \>1000-\<2500; Gr 3: \>800-\<1000; Gr 4: \<800. . Prothrombin time (seconds) Gr 1: 1.01-1.25\*ULN; Gr 2: 1.26-1.5\*ULN; Gr 3: 1.51-3\*ULN; Gr 4: \>3\*ULN.
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 While on treatment from Baseline through Week 96 Blood urea nitrogen Gr 1:1.25-2.5\*ULN;Gr 2:2.6-5.0\*ULN; Gr 3:5.1-10\*ULN; Gr 4:\>10\*ULN. Creatinine (mg/dL) Gr 1: 1.1-1.5 \*ULN; Gr 2: 1.6-3\*ULN: Gr 3: 3.1-6\*ULN; Gr 4: \>6\*ULN. Hypercarbia (meq/L)Gr 1: 33-36; Gr 2:37-40; Gr 3: 41-45; Gr 4:\>45. Hypocarbia (meq/L)Gr 1:19-21; Gr 2: 15-18; Gr 3: 10-14; Gr 4:\<10. Hypercalcemia (mg/dL)Gr 1:10.6-11.5;Gr 2:11.6-12.5; Gr 3:12.6-13.5;Gr 4: \>13.5. Hypocalcemia (mg/dL)Gr 1: 8.4-7.8;Gr 2:7.7-7; Gr 3:6.9-6.1; Gr 4: \<6.1.Hyperchloremia(meq/L)Gr 1:113-116; Gr 2:117-120; Gr 3:121-125; Gr 4: \>125.Hypochloremia(meq/L)Gr 1: 90-93; Gr 2: 85-89; Gr 3:80-84; Gr 4:\<80.
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) While on treatment from Baseline through Week 96 Hyperkalemia(meq/L) Gr 1: 5.6-6; Gr 2: 6.1-6.5; Gr 3: 6.6-7; Gr4: \>7. Hypokalemia(meq/L) Gr 1: 3-3.4; Gr 2: 2.5-2.9; Gr 3: 2-2.4; Gr 4:\<2. Hypernatremia (meq/L) Gr 1: 148-150; Gr 2: 151-157; Gr 3: 148-165; Gr 4: \>165. Hyponatremia (meq/L) Gr 1: 130-132; Gr 2: 123-129; Gr 3: 116-122; Gr 4: \>115.Hyperglycemia(mg/dL)Gr 1: 116-160; Gr 2: 161-250; Gr 3: 251-500; Gr 4: \>500. Hypoglycemia(mg/dL)Gr 1: 55-64; Gr 2: 40-54; Gr 3:30-39;Gr 4:\<30.Creatine kinase (IU/L) Gr 1: \>ULN-1.5\*ULN; Gr 2: 1.5-3\*ULN; Gr 3: \>3-6\*ULN; Gr 4: \>6.0\*ULN. Albumin (g/dL) Gr 1: \<LLN-30; Gr 2: \<30-20; Gr 3\&4: \<20.
Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 While on treatment from Baseline through Week 96 AST/SGOT=Aspartate aminotransferase/serum glutamate oxaloacetate transaminase; ALT/SGPT=Alanine transaminase/serum glutamic pyruvic transaminase. Bilirubin (mg/dL)Gr 1: 1.1-1.5\*ULN;Gr 2:1.6-2.5\*ULN;Gr3:2.6-5\*ULN;Gr4:\>5\*ULN.AST/SGOT(U/L)Gr 1:1.25-2.5\*ULN;Gr 2: 2.6-5\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN.ALT/SGPT (U/L)Gr 1:1.25-2.5\*ULN;Gr 2:1.4-2.09\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN. Lipase(U/L)Gr 1:1.1-1.39\*ULN;Gr 2:\>1.5-2\*ULN;Gr 3:2.5-5;Gr 4:5\*ULN.Proteinuria(g/24 hr loss)Gr 1:1+or \<1;Gr 2:2-3+or\>1-2; Gr 3:4+or\>2-3.5;Gr4:\>3.5.Creatine kinase(IU/L)Gr1:2-3\*ULN;Gr 2:3.1-5\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN.
Trial Locations
- Locations (10)
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Local Institution
🇫🇷Paris Cedex 20, France
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
The Aaron Diamond AIDS Research Center
🇺🇸New York, New York, United States
Southwest Center For HIV/AIDS
🇺🇸Phoenix, Arizona, United States
Dupont Circle Physicians Group
🇺🇸Washington, District of Columbia, United States
Therapeutic Concepts, P.A.
🇺🇸Houston, Texas, United States
Tarrant County Infectious Disease Associates
🇺🇸Ft Worth, Texas, United States
Diversified Medical Practices, P.A.
🇺🇸Houston, Texas, United States
University Of Cincinnati
🇺🇸Cincinnati, Ohio, United States