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 - Full Text View

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Atazanavir Atazanavir sulfate

U.S. FDA Resources

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:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

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:


Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Immune System Diseases Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Virus Diseases Atazanavir	HIV Protease Inhibitors Protease Inhibitors Ritonavir Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015

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)