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

Human Immunodeficiency Virus (HIV) Infections Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00337467
• Other study ID #: AI424-227
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2006
• Last updated: June 18, 2010
• Start date: June 2006
• Est. completion date: May 2009

Study information

• Verified date: June 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: May 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV) Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Atazanavir + Ritonavir
Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks

Locations

Country	Name	City	State
Spain	Local Institution	Cordoba
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24		Baseline, Week 24	No
Secondary	Mean Change From Baseline in CD4 Cell Count at Week 48		Baseline, Week 48	No
Secondary	Mean Change From Baseline in CD4 Cell Count at Week 96		Baseline, Week 96	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm