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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01332227
First received: April 7, 2011
Last updated: October 15, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
HIV, Combination Therapy
Drug: Atazanavir
Drug: Ritonavir (heat-stable)
Drug: Raltegravir
Drug: Tenofovir/Emtricitabine
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 24 [ Time Frame: From Day 1 to Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 48 [ Time Frame: From Day 1 to Week 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Virologic Rebound at Weeks 24 and 48 [ Time Frame: Day 1 to Weeks 28 and 48 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 1 to Week 24 ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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.

  • Mean Changes in Fasting Lipid Levels From Baseline to Week 48 [ Time Frame: From Baseline to Week 48 ] [ Designated as safety issue: Yes ]
    LD=low-density lipoprotein; HDL=high-density lipoprotein.


Enrollment: 132
Study Start Date: October 2011
Study Completion Date: February 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atazanavir/Ritonavir + Raltegravir
Atazanavir + Ritonavir (heat-stable) + Raltegravir
Drug: Atazanavir
Capsules, Oral, 300mg, Once daily, 48 weeks
Other Name: Reyataz
Drug: Ritonavir (heat-stable)
Tablets, Oral, 100 mg, Once daily, 48 weeks
Other Name: Norvir
Drug: Raltegravir
Tablets, Oral, 400 mg, Twice daily, 48 weeks
Other Name: Isentress
Atazanavir/Ritonavir + Tenofovir/Emtricitabine

Reference

Atazanavir + Ritonavir (heat-stable) + Tenofovir/Emtricitabine

Drug: Atazanavir
Capsules, Oral, 300mg, Once daily, 48 weeks
Other Name: Reyataz
Drug: Ritonavir (heat-stable)
Tablets, Oral, 100 mg, Once daily, 48 weeks
Other Name: Norvir
Drug: Tenofovir/Emtricitabine
Tablets, Oral, 300/200 mg, Once daily, 48 weeks
Other Name: Truvada

Detailed Description:

Allocation: Randomized nonstratified

Intervention model: Parallel versus comparator

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332227

  Show 38 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Mayers Squibb Bristol-Mayers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01332227     History of Changes
Other Study ID Numbers: AI424-402, 2009-017032-41
Study First Received: April 7, 2011
Results First Received: September 19, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Ministry of Health
Italy: The Italian Medicines Agency
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

ClinicalTrials.gov processed this record on October 29, 2014