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)

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV) Infections
• Intervention / Treatment: Drug: Atazanavir + Ritonavir

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Cordoba, Spain, 14004
    • Local Institution
  • Madrid, Spain, 28041
    • Local Institution
  • Madrid, Spain, 28034
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1	Drug: Atazanavir + Ritonavir; Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks; Other Names: Reyataz; BMS-232632

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Failure Through Week 48	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.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Failure Through Week 96	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.	Week 96
Percentage of Participants With Virological Rebound Through Week 48	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.	Week 48
Percentage of Participants With Virological Rebound Through Week 96	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.	Week 96
Cumulative Proportion of Participants Without Treatment Failure Through Week 100	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).	Through Week 100
Proportion of Participants With Virologic Rebound Through Week 96	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.	Through Week 96
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24		Baseline, Week 24
Mean Change From Baseline in CD4 Cell Count at Week 48		Baseline, Week 48
Mean Change From Baseline in CD4 Cell Count at Week 96		Baseline, Week 96
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs	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).	From Baseline through Week 96
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	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.	Baseline, Week 48
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	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.	Baseline, Week 96
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48	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.	Week 48
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96	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.	Week 96

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: June 14, 2006
• First Submitted That Met QC Criteria: June 15, 2006
• First Posted (Estimate): June 16, 2006

Study Record Updates

• Last Update Posted (Estimate): July 19, 2010
• Last Update Submitted That Met QC Criteria: June 18, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: HIV-Infected Patients Evidencing Virologic Suppression
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: AI424-227