Clinical trial NCT00768989: Phase IIB Pilot of Atazanavir + Raltegravir
Official title: A Multicenter, Randomized, Open-Label, Active-Controlled Pilot Study to Evaluate the Safety and Antiretroviral Activity of Unboosted Atazanavir BID Plus Raltegravir BID and Boosted Atazanavir QD in Combination With Tenofovir/Emtricitabine QD in Treatment Naive HIV-Infected Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV
Keywords: Combination Therapy
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-10-08
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the combination of atazanavir and raltegravir taken together is safe and effective in the treatment of human immunodeficiency virus (HIV).


Eligibility criteria: Inclusion Criteria:

* Human Immunodeficiency Virus (HIV)-1 positive status
* HIV ribonucleic acid (RNA) level \>=5000 copies/mL
* Antiretroviral treatment-naive
* Absolute Cluster of Differentiation 4 (CD4) cell count meeting 1 of the following criteria:
* \<350 cells/mm\^3
* Screening CD4 \>=350 and \<=500 cells/mm\^3 ONLY if at least 1 of the following conditions apply:

  * Screening HIV RNA level \>100,000 copies/mL, or
  * CD4 decline \>50-100 cells/mm\^3/year, or
  * Age \>=55 years
* Any CD4 cell count, if participant has a history of an acquired immune deficiency syndrome-defining illness
* Medically stable

Exclusion Criteria:

* Screening HIV genotype showing resistance to any component of the study regimen (Atazanavir, Raltegravir, Tenofovir/Emtricitabine)
* Hepatitis B or hepatitis C coinfection
* History of or current cardiac disease
* Electrocardiogram findings:
* PR Interval \>260 msec (severe 1st degree atrioventricular block)
* QRS Interval \>120 msec

Primary outcomes:
measure: Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24
timeFrame: At Week 24 from Baseline
Secondary outcomes:
measure: Number of Nonresponders at Week 8
timeFrame: At Week 8 from Baseline
measure: Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96
timeFrame: At Weeks 48 and 96 from Baseline
measure: Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24
timeFrame: At Week 24 from Baseline
measure: Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48
timeFrame: At Week 48 from Baseline
measure: Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96
timeFrame: At Week 96 from Baseline
measure: Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count
timeFrame: From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation
timeFrame: Week 1 to Week 96, continuously
measure: Baseline and Mean Change From Baseline in Total Cholesterol Levels
timeFrame: From Baseline to Week 24 and Week 48
measure: Mean Change From Baseline in Total Bilirubin Level
timeFrame: From Baseline to Week 24 and Week 48
measure: Mean Change From Baseline in Electrocardiogram Findings
timeFrame: From Baseline to Week 24
measure: Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval
timeFrame: At Week 2 from Baseline
measure: Raltegravir Cmax in 1 Dosing Interval
timeFrame: At Week 2 from Baseline
measure: Atazanavir Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: At Week 2 from Baseline
measure: Raltegravir Tmax
timeFrame: At Week 2 from Baseline
measure: Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose
timeFrame: At Week 2 from Baseline
measure: Raltegravir Cmin 12 Hours Postdose
timeFrame: At Week 2 from Baseline
measure: Atazanavir Cmin Prior to the Morning Dose
timeFrame: At Week 2 from Baseline
measure: Raltegravir Cmin Prior to the Morning Dose
timeFrame: At Week 2 from Baseline
measure: Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval
timeFrame: At Week 2 from Baseline
measure: Raltegravir AUC (0-12h) in 1 Dosing Interval
timeFrame: At Week 2 from Baseline
measure: Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval
timeFrame: At Week 2 from Baseline
measure: Atazanavir Individual Inhibitory Quotient (IQ)
timeFrame: At Week 2 from Baseline
measure: Atazanavir Terminal Elimination Half Life
timeFrame: At Week 2 from Baseline
measure: Raltegravir Terminal Elimination Half Life
timeFrame: At Week 2 from Baseline
measure: Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants
timeFrame: While on treatment from Baseline through Week 96
measure: Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4
timeFrame: While on treatment from Baseline through Week 96
measure: Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued)
timeFrame: While on treatment from Baseline through Week 96
measure: Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4
timeFrame: While on treatment from Baseline through Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Center For HIV/AIDS
state: Arizona
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: New York
country: United States
facility: The Aaron Diamond AIDS Research Center
state: New York
city: Cincinnati
country: United States
facility: University Of Cincinnati
state: Ohio
city: Ft Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, P.A.
state: Texas
city: Houston
country: United States
facility: Diversified Medical Practices, P.A.
state: Texas
city: Buenos Aires, Bs As
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: Nantes Cedex 01
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Paris Cedex 20
country: France
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kozal MJ, Lupo S, DeJesus E, Molina JM, McDonald C, Raffi F, Benetucci J, Mancini M, Yang R, Wirtz V, Percival L, Zhang J, Zhu L, Arikan D, Farajallah A, Nguyen BY, Leavitt R, McGrath D, Lataillade M, The Spartan Study Team. A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naive HIV-infected patients: SPARTAN study results. HIV Clin Trials. 2012 May-Jun;13(3):119-30. doi: 10.1310/hct1303-119.