Phase IIB Pilot of Atazanavir + Raltegravir (SPARTAN)

A Multicenter, Randomized, Open-Label, Active-Controlled Pilot Study to Evaluate the Safety and Antiretroviral Activity of Unboosted Atazanavir BID Plus Raltegravir BID and Boosted Atazanavir QD in Combination With Tenofovir/Emtricitabine QD in Treatment Naive HIV-Infected Subjects

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).

Study Overview

• Status: Terminated
• Conditions: HIV
• Intervention / Treatment: Drug: Atazanavir; Drug: Raltegravir; Drug: Atazanavir; Drug: Ritonavir; Drug: Tenofovir/Emtricitabine

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Buenos Aires, Bs As, Buenos Aires, Argentina, 1141
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1264
      • Local Institution
    • Mar Del Plata, Buenos Aires, Argentina, B7600CTO
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Local Institution
• France
  • Nantes Cedex 01, France, 44035
    • Local Institution
  • Paris Cedex 10, France, 75475
    • Local Institution
  • Paris Cedex 20, France, 75970
    • Local Institution
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Center For Hiv/Aids
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group
  • Florida
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • New York
    • New York, New York, United States, 10016
      • The Aaron Diamond AIDS Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Texas
    • Ft Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, P.A.
    • Houston, Texas, United States, 77057
      • Diversified Medical Practices, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atazanavir + Raltegravir; Atazanavir 300 mg twice daily + Raltegravir 400 mg twice daily	Drug: Atazanavir; Capsules, Oral, 300 mg, twice daily, 96 weeks; Other Names: Reyataz; BMS-232632; Drug: Raltegravir; Tablet, Oral, 400 mg, twice daily, 96 weeks; Drug: Atazanavir; Capsules, Oral, 300 mg, once daily, 96 weeks; Other Names: Reyataz; BMS-232632
Active Comparator: Atazanavir + Ritonavir + Tenofovir /Emtricitabine; Atazanavir, 300 mg once daily, + Ritonavir, 100 mg once daily, + Tenofovir 300 mg/Emtricitabine, 200 mg once daily	Drug: Atazanavir; Capsules, Oral, 300 mg, twice daily, 96 weeks; Other Names: Reyataz; BMS-232632; Drug: Atazanavir; Capsules, Oral, 300 mg, once daily, 96 weeks; Other Names: Reyataz; BMS-232632; Drug: Ritonavir; Capsules, Oral, 100 mg, once daily, 96 weeks; Drug: Tenofovir/Emtricitabine; Tablet, Oral, 300-mg Tenofovir/200-mg Emtricitabine, once daily, 96 weeks; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24	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).	At Week 24 from Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Nonresponders at Week 8	Participants were classified as nonresponders if they had an HIV RNA level ≥400 copies/mL and a decrease from baseline <2 log10 copies/mL.	At Week 8 from Baseline
Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96	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.	At Weeks 48 and 96 from Baseline
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24	NC=F: noncompleter=failure; NC=M: noncompleter=missing; VR-OC: virologic response-observed	At Week 24 from Baseline
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	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.	Week 1 to Week 96, continuously
Baseline and Mean Change From Baseline in Total Cholesterol Levels	The mean change from baseline in participant fasting lipids was determined using fasting serum samples.	From Baseline to Week 24 and Week 48
Mean Change From Baseline in Total Bilirubin Level		From Baseline to Week 24 and Week 48
Mean Change From Baseline in Electrocardiogram Findings	The incidence of QRS wave widening and QT and PR prolongation on participant electrocardiogram findings were evaluated at study Week 24.	From Baseline to Week 24
Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline
Raltegravir Cmax in 1 Dosing Interval	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline
Atazanavir Time of Maximum Observed Plasma Concentration (Tmax)	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline
Raltegravir Tmax	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline
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	AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2.	At Week 2 from Baseline
Atazanavir Individual Inhibitory Quotient (IQ)	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.	At Week 2 from Baseline
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	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.	While on treatment from Baseline through Week 96
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4	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.	While on treatment from Baseline through Week 96
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued)	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.	While on treatment from Baseline through Week 96
Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4	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.	While on treatment from Baseline through Week 96

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kozal MJ, Lupo S, DeJesus E, Molina JM, McDonald C, Raffi F, Benetucci J, Mancini M, Yang R, Wirtz V, Percival L, Zhang J, Zhu L, Arikan D, Farajallah A, Nguyen BY, Leavitt R, McGrath D, Lataillade M, The Spartan Study Team. A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naive HIV-infected patients: SPARTAN study results. HIV Clin Trials. 2012 May-Jun;13(3):119-30. doi: 10.1310/hct1303-119.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): February 24, 2012
• Last Update Submitted That Met QC Criteria: February 22, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Combination Therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: AI424-376