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 Sharp & Dohme Corp.
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

October 6, 2008
February 22, 2012
November 2008
January 2010   (final data collection date for primary outcome measure)
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).
Proportion of subjects with HIV RNA <50 c/mL [ Time Frame: at Week 24 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00768989 on ClinicalTrials.gov Archive Site
  • 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.
  • Proportions of subjects with HIV RNA <50 [ Time Frame: at Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Antiretroviral activity [ Time Frame: at Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
  • Safety as measured by adverse events, laboratory abnormalities and ECG findings [ Time Frame: through Weeks 24, 48, and 96 ] [ Designated as safety issue: Yes ]
  • Assessment of pharmacokinetics [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase IIB Pilot of Atazanavir + Raltegravir
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).

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • 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
  • 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
  • Experimental: Atazanavir + Raltegravir
    Atazanavir 300 mg twice daily + Raltegravir 400 mg twice daily
    Interventions:
    • Drug: Atazanavir
    • Drug: Raltegravir
  • Active Comparator: Atazanavir + Ritonavir + Tenofovir /Emtricitabine
    Atazanavir, 300 mg once daily, + Ritonavir, 100 mg once daily, + Tenofovir 300 mg/Emtricitabine, 200 mg once daily
    Interventions:
    • Drug: Atazanavir
    • Drug: Ritonavir
    • Drug: Tenofovir/Emtricitabine
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-naïve HIV-infected patients: SPARTAN study results. HIV Clin Trials. 2012 May-Jun;13(3):119-30. doi: 10.1310/hct1303-119.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
167
May 2010
January 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   France
 
NCT00768989
AI424-376
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP