Atazanavir/Ritonavir, Once Daily + Raltegravir, Twice Daily, Switch Study in HIV-1-Infected Patients (SPARTAN)

An Open-Label, Randomized Study Evaluating a Switch From a Regimen of Two Nucleoside Reverse Transcriptase Inhibitors Regimen Plus Any Third Agent to Either a Regimen of Atazanavir/Ritonavir Once Daily and Raltegravir Twice Daily or to a Regimen of Atazanavir/Ritonavir Once Daily and Tenofovir/Emtricitabine Once Daily in Virologically Suppressed HIV-1 Infected Subjects With Safety and/or Tolerability Issues on Their Present Treatment Regimen.

The purpose of this study is to determine whether HIV-1-infected patients, who are virologically suppressed on a regimen of 2 nucleoside reverse transcriptase inhibitors plus any third agent but are experiencing safety and/or tolerability issues, will maintain virologic suppression after switching to a regimen of heat-stable ritonavir boosted atazanavir, 300/100 mg, once daily plus raltegravir, 400 mg, twice daily.

Study Overview

• Status: Completed
• Conditions: HIV, Combination Therapy
• Intervention / Treatment: Drug: Atazanavir; Drug: Ritonavir (heat-stable); Drug: Raltegravir; Drug: Tenofovir/Emtricitabine

Detailed Description

Allocation: Randomized nonstratified

Intervention model: Parallel versus comparator

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyons Cedex 04, France, 69317
    • Local Institution
  • Orleans Cedex 2, France, 45067
    • Local Institution
  • Paris, France, 75020
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Strasbourg Cedex, France, 67091
    • Local Institution
  • Cedex 12
    • Paris, Cedex 12, France, 75551
      • Local Institution
• Germany
  • Bochum, Germany, 44791
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Frankfurt Am Main, Germany, 60311
    • Local Institution
  • Hamburg, Germany, 20246
    • Local Institution
  • Munich, Germany, 80336
    • Local Institution
• Italy
  • Genova, Italy, 16128
    • Local Institution
  • Genova, Italy, 16132
    • Local Institution
  • Milano, Italy, 20127
    • Local Institution
  • Milano, Italy, 20142
    • Local Institution
  • Roma, Italy, 00149
    • Local Institution
• Poland
  • Warszawa, Poland, 01-201
    • Local Institution
  • Wroclaw, Poland, 50-136
    • Local Institution
• Spain
  • Alicante, Spain, 03010
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution
  • Madrid, Spain, 28006
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Madrid, Spain, 28805
    • Local Institution
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Local Institution
  • London, United Kingdom, E9 6SR
    • Local Institution
  • London, United Kingdom, NW3 2QG
    • Local Institution
  • Sheffield, United Kingdom, S10 2RX
    • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, SW10 9EL
      • Local Institution
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M8 5RB
      • Local Institution
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health For Life Clinic Pllc
  • California
    • Palm Springs, California, United States, 92264
      • Eisenhower Medical Center
    • San Francisco, California, United States, 94109
      • Metropolis Medical Pc
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Consultive Medicine
    • Orlando, Florida, United States, 32805
      • Orange County Health Dept.
    • West Palm Beach, Florida, United States, 33401
      • Triple O Medical Services, P.A.
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
  • New York
    • Rochester, New York, United States, 14607
      • Aids Care

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

Key Inclusion Criteria

• Current treatment regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus any third agent for at least 3 months immediately prior to screening
• Virologic suppression (HIV-1 RNA <50 c/mL) for at least 3 months immediately prior to screening
• Virologic suppression (HIV-1 RNA <40 c/mL) using the Abbott m2000rt® polymerase chain reaction assay during screening period
• Treatment-related safety and/or tolerability issues to a regimen consisting of 2 NRTIs plus any third agent

Key Exclusion Criteria

• History of switch in highly active antiretroviral therapy due to virologic failure
• History of genotypic resistance to any component of the study regimen (atazanavir, raltegravir, tenofovir/emtricitabine)
• History of exposure to atazanavir/ritonavir or raltegravir prior to entering the study
• Experiencing safety and/or tolerability issues to tenofovir/emtricitabine or raltegravir
• Switch of any component of HIV antiretroviral medication regimen in the last 3 months immediately prior to or during the screening period

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/Ritonavir + Raltegravir; Atazanavir + Ritonavir (heat-stable) + Raltegravir	Drug: Atazanavir; Capsules, Oral, 300mg, Once daily, 48 weeks; Other Names: Reyataz; Drug: Ritonavir (heat-stable); Tablets, Oral, 100 mg, Once daily, 48 weeks; Other Names: Norvir; Drug: Raltegravir; Tablets, Oral, 400 mg, Twice daily, 48 weeks; Other Names: Isentress
Other: Atazanavir/Ritonavir + Tenofovir/Emtricitabine; Reference Atazanavir + Ritonavir (heat-stable) + Tenofovir/Emtricitabine	Drug: Atazanavir; Capsules, Oral, 300mg, Once daily, 48 weeks; Other Names: Reyataz; Drug: Ritonavir (heat-stable); Tablets, Oral, 100 mg, Once daily, 48 weeks; Other Names: Norvir; Drug: Tenofovir/Emtricitabine; Tablets, Oral, 300/200 mg, Once daily, 48 weeks; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 24	HIV-1 RNA level was measured with the Abbott m2000rt® polymerase chain reaction assay. Response rates were assessed using an intent-to-treat algorithm, with numerator representing patients meeting the response criteria, and denominator representing all randomized patients. Randomized patients not meeting the criteria for treatment failure (eg, discontinuation of study therapy or virologic rebound at or before Week 24) were considered responders. Virologic rebound was defined as 2 consecutive on-treatment HIV-1 RNA levels ≥40 c/mL or the last on-treatment HIV-1 RNA level ≥40 c/mL followed by discontinuation. Patients who experienced treatment failure or had missing Week 24 HIV-1 RNA levels were considered failures. RNA=ribonucleic acid; HIV=human immunodeficiency virus.	From Day 1 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 48	Percentages of patients with HIV-1 RNA levels <40 c/mL were summarized at each scheduled visit. Longitudinal plots were created to display proportion versus visit week through Weeks 24 and 48 with error bars representing 95% confidence intervals.	From Day 1 to Week 48
Number of Participants With Virologic Rebound at Weeks 24 and 48	Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates.	Day 1 to Weeks 28 and 48
Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 24	Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients	Day 1 to Week 24
Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 48	Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients	Day 1 to Week 48
Number of Patients With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Treatment-emergent Adverse Events (AEs) Leading to Discontinuation, and Treatment-emergent AEs	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. Related=having certain, probable, possible, or unknown relationship to study drug.	Day 1 to Week 48
Mean Changes in Fasting Lipid Levels From Baseline to Week 48	LD=low-density lipoprotein; HDL=high-density lipoprotein.	From Baseline to Week 48

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Mayers Squibb, Bristol-Mayers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 8, 2011
• First Posted (Estimate): April 11, 2011

Study Record Updates

• Last Update Posted (Estimate): February 19, 2015
• Last Update Submitted That Met QC Criteria: February 2, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• 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: AI424-402; 2009-017032-41 (EudraCT Number)