Back to resultsPhase 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)
Primary Purpose
Human Immunodeficiency Virus (HIV) Infections
Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Atazanavir + Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus (HIV) Infections focused on measuring HIV-Infected Patients Evidencing Virologic Suppression
Eligibility 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.
Sites / Locations
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A1
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
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.
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24
Mean Change From Baseline in CD4 Cell Count at Week 48
Mean Change From Baseline in CD4 Cell Count at 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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00337467
Brief Title
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
Acronym
OREY
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus (HIV) Infections
Keywords
HIV-Infected Patients Evidencing Virologic Suppression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Atazanavir + Ritonavir
Other Intervention Name(s)
Reyataz, BMS-232632
Intervention Description
Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment Failure Through Week 48
Description
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.
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With Treatment Failure Through Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With Virological Rebound Through Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With Virological Rebound Through Week 96
Description
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.
Time Frame
Week 96
Title
Cumulative Proportion of Participants Without Treatment Failure Through Week 100
Description
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).
Time Frame
Through Week 100
Title
Proportion of Participants With Virologic Rebound Through Week 96
Description
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.
Time Frame
Through Week 96
Title
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24
Time Frame
Baseline, Week 24
Title
Mean Change From Baseline in CD4 Cell Count at Week 48
Time Frame
Baseline, Week 48
Title
Mean Change From Baseline in CD4 Cell Count at Week 96
Time Frame
Baseline, Week 96
Title
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs
Description
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).
Time Frame
From Baseline through Week 96
Title
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
Description
Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Time Frame
Baseline, Week 48
Title
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
Description
Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Time Frame
Baseline, Week 96
Title
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48
Description
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.
Time Frame
Week 48
Title
Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96
Description
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.
Time Frame
Week 96
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Local Institution
City
Malaga
ZIP/Postal Code
29010
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs