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Phase IIB Pilot of Atazanavir + Raltegravir (SPARTAN)

This study has been terminated.
(Efficacy endpoint met, but overall experimental dosing regimen not considered optimal to support further clinical development in this population.)
Sponsor:
Collaborator:
Merck
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00768989
First received: October 6, 2008
Last updated: February 22, 2012
Last verified: February 2012
History of Changes
  Purpose

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).


Condition Intervention Phase
HIV
 Drug: Atazanavir
Drug: Raltegravir
Drug: Ritonavir
Drug: Tenofovir/Emtricitabine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 [ Time Frame: At Week 24 from Baseline ] [ Designated as safety issue: No ]
    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:
  • Number of Nonresponders at Week 8 [ Time Frame: At Week 8 from Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Weeks 48 and 96 from Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 24 from Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 48 from Baseline ] [ Designated as safety issue: No ]
  • Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96 [ Time Frame: At Week 96 from Baseline ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count [ Time Frame: From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation [ Time Frame: Week 1 to Week 96, continuously ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From Baseline to Week 24 and Week 48 ] [ Designated as safety issue: No ]
    The mean change from baseline in participant fasting lipids was determined using fasting serum samples.

  • Mean Change From Baseline in Total Bilirubin Level [ Time Frame: From Baseline to Week 24 and Week 48 ] [ Designated as safety issue: Yes ]
  • Mean Change From Baseline in Electrocardiogram Findings [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.

  • Raltegravir Cmax in 1 Dosing Interval [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    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) [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.

  • Raltegravir Tmax [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Raltegravir Cmin 12 Hours Postdose [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Atazanavir Cmin Prior to the Morning Dose [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Raltegravir Cmin Prior to the Morning Dose [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Raltegravir AUC (0-12h) in 1 Dosing Interval [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2.

  • Atazanavir Individual Inhibitory Quotient (IQ) [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Raltegravir Terminal Elimination Half Life [ Time Frame: At Week 2 from Baseline ] [ Designated as safety issue: No ]
  • Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants [ Time Frame: While on treatment from Baseline through Week 96 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: While on treatment from Baseline through Week 96 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: While on treatment from Baseline through Week 96 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: While on treatment from Baseline through Week 96 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 167
Study Start Date: November 2008
Study Completion Date: May 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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, 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 Name: Truvada

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00768989

Locations
United States, Arizona
Southwest Center For HIV/AIDS
Phoenix, Arizona, United States, 85006
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Dupont Circle Physicians Group
Washington, District of Columbia, United States, 20009
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, New York
The Aaron Diamond AIDS Research Center
New York, New York, United States, 10016
United States, Ohio
University Of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Texas
Tarrant County Infectious Disease Associates
Ft Worth, Texas, United States, 76104
Diversified Medical Practices, P.A.
Houston, Texas, United States, 77057
Therapeutic Concepts, P.A.
Houston, Texas, United States, 77004
Argentina
Local Institution
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
Rosario, Santa Fe, Argentina, 2000
France
Local Institution
Nantes Cedex 01, France, 44035
Local Institution
Paris Cedex 10, France, 75475
Local Institution
Paris Cedex 20, France, 75970
Sponsors and Collaborators
Bristol-Myers Squibb
Merck
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00768989     History of Changes
Other Study ID Numbers: AI424-376
Study First Received: October 6, 2008
Results First Received: October 19, 2011
Last Updated: February 22, 2012
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
Combination Therapy

Additional relevant MeSH terms:
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013