Phase IIIb Study to Evaluate the Effectiveness and Safety of Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in Human Immunodeficiency Virus (HIV)-Infected Subjects Evidencing Virologic Suppression (OREY)

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00337467
First received: June 14, 2006
Last updated: June 18, 2010
Last verified: June 2010
  Purpose

The main purpose is to explore whether atazanavir/ritonavir (ATV/RTV) single enhanced protease inhibitor therapy can maintain virologic suppression without a marked increase in virologic failure.


Condition Intervention Phase
Human Immunodeficiency Virus (HIV) Infections
Drug: Atazanavir + Ritonavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIIb Multicenter, Single Arm, Open-Label Pilot Study to Evaluate the Effectiveness and Safety of Maintenance With Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in HIV-Infected Patients Evidencing Virologic Suppression OREY (Only REYataz) Study

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants With Treatment Failure Through Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Treatment Failure through Week 48 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy.


Secondary Outcome Measures:
  • Percentage of Participants With Treatment Failure Through Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Treatment Failure through Week 96 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 96 or study discontinuation before Week 96. In addition, treatment failure defined based on HIV RNA >= 50 c/mL, latter analysis performed on treated subjects with baseline HIV RNA < 50 c/mL.

  • Percentage of Participants With Virological Rebound Through Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.

  • Percentage of Participants With Virological Rebound Through Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.

  • Cumulative Proportion of Participants Without Treatment Failure Through Week 100 [ Time Frame: Through Week 100 ] [ Designated as safety issue: No ]
    This Kaplan-Meier life table reports the cumulative proportion of participants without treatment failure up to the end of the respective time interval. Failure time is measured from the start of study therapy, and is based on the earliest event defining failure (virologic rebound at or before Week 96, or discontinuation prior to Week 96).

  • Proportion of Participants With Virologic Rebound Through Week 96 [ Time Frame: Through Week 96 ] [ Designated as safety issue: No ]
    Virologic rebound is defined as confirmed on-study HIV RNA ≥ 400 c/mL or last on-study HIV RNA ≥ 400 c/mL followed by treatment discontinuation.

  • Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs [ Time Frame: From Baseline through Week 96 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship to treatment. SAE=any untoward medical occurrence that 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, or is an important medical event. AE grades are: mild (1), moderate (2), severe (3), life-threatening (4), and death (5).

  • Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: Yes ]
    Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.

  • Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: Yes ]
    Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.

  • Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.

  • Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.


Enrollment: 61
Study Start Date: June 2006
Study Completion Date: May 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1 Drug: Atazanavir + Ritonavir
Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks
Other Names:
  • Reyataz
  • BMS-232632

  Eligibility

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

Inclusion Criteria:

  • On continued antiretroviral (ARV) treatment, with no discontinuation periods, for the previous 6 months (24 weeks).
  • Absence of evidence or suspected virologic failure on antiretroviral therapy
  • Absence of known primary mutations in the protease gene
  • Only 1 highly active antiretroviral therapy (HAART) prior to current one
  • HIV RNA < 50 copies/mL in the last 6 months (single blip below 200 c/mL allowed)
  • On ATV/RTV +2 nucleoside reverse transcriptase inhibitors (NRTIs) (or 1 NRTI + tenofovir [TDF]) for at least 8 weeks before study entry, without treatment-limiting adverse effects

Exclusion Criteria:

  • Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
  • Active disease condition (e.g. moderate to severe hepatic impairment/active renal disease/history of clinically significant heart conduction disease)
  • Patients with chronic hepatitis B receiving lamivudine (3TC), Tenofovir Disoproxil Fumarate (TDF) or emtricitabine (FTC).
  • CD4 < 100 cells/mm3
  • Grade IV laboratory values: Hemoglobin < 6.5 g/dL or white blood cells (WBC) <800/mmm3 or absolute neutrophil count < 500/mm3, or platelets < 20,000/mm3 or diffuse petechiae.
  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: NCT00337467

Locations
Spain
Local Institution
Cordoba, Spain, 14004
Local Institution
Madrid, Spain, 28041
Local Institution
Madrid, Spain, 28046
Local Institution
Madrid, Spain, 28007
Local Institution
Madrid, Spain, 28040
Local Institution
Madrid, Spain, 28034
Local Institution
Malaga, Spain, 29010
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00337467     History of Changes
Other Study ID Numbers: AI424-227
Study First Received: June 14, 2006
Results First Received: May 21, 2010
Last Updated: June 18, 2010
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Bristol-Myers Squibb:
HIV-Infected Patients Evidencing Virologic Suppression

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
Atazanavir
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

ClinicalTrials.gov processed this record on October 01, 2014