Phase IIB Pilot of Atazanavir + Raltegravir

HIV Clinical Trial

— SPARTAN  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00768989
• Other study ID #: AI424-376
• Status: Terminated
• Phase: Phase 2
• First received: October 6, 2008
• Last updated: February 22, 2012
• Start date: November 2008
• Est. completion date: May 2010

Study information

• Verified date: February 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 167
• Est. completion date: May 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Atazanavir
Capsules, Oral, 300 mg, twice daily, 96 weeks
• Raltegravir
Tablet, Oral, 400 mg, twice daily, 96 weeks
• Atazanavir
Capsules, Oral, 300 mg, once daily, 96 weeks
• Ritonavir
Capsules, Oral, 100 mg, once daily, 96 weeks
• Tenofovir/Emtricitabine
Tablet, Oral, 300-mg Tenofovir/200-mg Emtricitabine, once daily, 96 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires, Bs As	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
France	Local Institution	Nantes Cedex 01
France	Local Institution	Paris Cedex 10
France	Local Institution	Paris Cedex 20
United States	University Of Cincinnati	Cincinnati	Ohio
United States	Tarrant County Infectious Disease Associates	Ft Worth	Texas
United States	Diversified Medical Practices, P.A.	Houston	Texas
United States	Therapeutic Concepts, P.A.	Houston	Texas
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	The Aaron Diamond AIDS Research Center	New York	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	Southwest Center For HIV/AIDS	Phoenix	Arizona
United States	Dupont Circle Physicians Group	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Argentina,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24	The number of HIV 1-infected treatment-naive participants with an HIV RNA level <50 copies/mL after 24 weeks of treatment. Confirmed virologic response noncompleter=failure (NC=F); noncompleter=missing (NC=M); virologic response-observed cases (VR-OC).	At Week 24 from Baseline	No
Secondary	Number of Nonresponders at Week 8	Participants were classified as nonresponders if they had an HIV RNA level =400 copies/mL and a decrease from baseline <2 log10 copies/mL.	At Week 8 from Baseline	No
Secondary	Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96	Participant HIV RNA level was determined at Weeks 48 and 96 using the Roche Amplicor® Ultrasensitive Assay Version 1. VR-OC=Virologic response-observed cases.	At Weeks 48 and 96 from Baseline	No
Secondary	Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24	NC=F: noncompleter=failure; NC=M: noncompleter=missing; VR-OC: virologic response-observed	At Week 24 from Baseline	No
Secondary	Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48		At Week 48 from Baseline	No
Secondary	Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96		At Week 96 from Baseline	No
Secondary	Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count		From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24	No
Secondary	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose 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, results in drug dependency or drug abuse, or is an important medical event.	Week 1 to Week 96, continuously	Yes
Secondary	Baseline and Mean Change From Baseline in Total Cholesterol Levels	The mean change from baseline in participant fasting lipids was determined using fasting serum samples.	From Baseline to Week 24 and Week 48	No
Secondary	Mean Change From Baseline in Total Bilirubin Level		From Baseline to Week 24 and Week 48	Yes
Secondary	Mean Change From Baseline in Electrocardiogram Findings	The incidence of QRS wave widening and QT and PR prolongation on participant electrocardiogram findings were evaluated at study Week 24.	From Baseline to Week 24	Yes
Secondary	Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline	No
Secondary	Raltegravir Cmax in 1 Dosing Interval	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline	No
Secondary	Atazanavir Time of Maximum Observed Plasma Concentration (Tmax)	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline	No
Secondary	Raltegravir Tmax	Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.	At Week 2 from Baseline	No
Secondary	Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose		At Week 2 from Baseline	No
Secondary	Raltegravir Cmin 12 Hours Postdose		At Week 2 from Baseline	No
Secondary	Atazanavir Cmin Prior to the Morning Dose		At Week 2 from Baseline	No
Secondary	Raltegravir Cmin Prior to the Morning Dose		At Week 2 from Baseline	No
Secondary	Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval		At Week 2 from Baseline	No
Secondary	Raltegravir AUC (0-12h) in 1 Dosing Interval		At Week 2 from Baseline	No
Secondary	Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval	AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2.	At Week 2 from Baseline	No
Secondary	Atazanavir Individual Inhibitory Quotient (IQ)	Individual IQ was defined at Cmin at Week 2 divided by the protein binding adjusted EC90 (ie, the drug concentration observed to inhibit virion production by 90% in a cell-based assay) values for Atazanavir that were derived from individual participant clinical isolates.	At Week 2 from Baseline	No
Secondary	Atazanavir Terminal Elimination Half Life		At Week 2 from Baseline	No
Secondary	Raltegravir Terminal Elimination Half Life		At Week 2 from Baseline	No
Secondary	Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants	ULN=upper limit of normal. Hematocrit(%) Grade (Gr) 1: =28.5-<31; Gr 2: =24-<28.5; Gr 3: =19.5-<24; Gr 4: <19.5. Hemoglobin (g/dL) Gr 1: 9.5-11; Gr 2: 8-9.4; Gr 3: 6.5-7.9; Gr 4: <6.5. Platelets (/mm^3) Gr 1: 75,000-99,000; Gr 2: 50,000-74,999; Gr 3: 20,000-49,999; Gr 4: <20,000. White Blood Cells (/mm^3) Gr 1: >2500-4000; Gr 2: >1000-<2500; Gr 3: >800-<1000; Gr 4: <800. . Prothrombin time (seconds) Gr 1: 1.01-1.25*ULN; Gr 2: 1.26-1.5*ULN; Gr 3: 1.51-3*ULN; Gr 4: >3*ULN.	While on treatment from Baseline through Week 96	Yes
Secondary	Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4	Blood urea nitrogen Gr 1:1.25-2.5*ULN;Gr 2:2.6-5.0*ULN; Gr 3:5.1-10*ULN; Gr 4:>10*ULN. Creatinine (mg/dL) Gr 1: 1.1-1.5 *ULN; Gr 2: 1.6-3*ULN: Gr 3: 3.1-6*ULN; Gr 4: >6*ULN. Hypercarbia (meq/L)Gr 1: 33-36; Gr 2:37-40; Gr 3: 41-45; Gr 4:>45. Hypocarbia (meq/L)Gr 1:19-21; Gr 2: 15-18; Gr 3: 10-14; Gr 4:<10. Hypercalcemia (mg/dL)Gr 1:10.6-11.5;Gr 2:11.6-12.5; Gr 3:12.6-13.5;Gr 4: >13.5. Hypocalcemia (mg/dL)Gr 1: 8.4-7.8;Gr 2:7.7-7; Gr 3:6.9-6.1; Gr 4: <6.1.Hyperchloremia(meq/L)Gr 1:113-116; Gr 2:117-120; Gr 3:121-125; Gr 4: >125.Hypochloremia(meq/L)Gr 1: 90-93; Gr 2: 85-89; Gr 3:80-84; Gr 4:<80.	While on treatment from Baseline through Week 96	Yes
Secondary	Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued)	Hyperkalemia(meq/L) Gr 1: 5.6-6; Gr 2: 6.1-6.5; Gr 3: 6.6-7; Gr4: >7. Hypokalemia(meq/L) Gr 1: 3-3.4; Gr 2: 2.5-2.9; Gr 3: 2-2.4; Gr 4:<2. Hypernatremia (meq/L) Gr 1: 148-150; Gr 2: 151-157; Gr 3: 148-165; Gr 4: >165. Hyponatremia (meq/L) Gr 1: 130-132; Gr 2: 123-129; Gr 3: 116-122; Gr 4: >115.Hyperglycemia(mg/dL)Gr 1: 116-160; Gr 2: 161-250; Gr 3: 251-500; Gr 4: >500. Hypoglycemia(mg/dL)Gr 1: 55-64; Gr 2: 40-54; Gr 3:30-39;Gr 4:<30.Creatine kinase (IU/L) Gr 1: >ULN-1.5*ULN; Gr 2: 1.5-3*ULN; Gr 3: >3-6*ULN; Gr 4: >6.0*ULN. Albumin (g/dL) Gr 1:	While on treatment from Baseline through Week 96	Yes
Secondary	Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4	AST/SGOT=Aspartate aminotransferase/serum glutamate oxaloacetate transaminase; ALT/SGPT=Alanine transaminase/serum glutamic pyruvic transaminase. Bilirubin (mg/dL)Gr 1: 1.1-1.5*ULN;Gr 2:1.6-2.5*ULN;Gr3:2.6-5*ULN;Gr4:>5*ULN.AST/SGOT(U/L)Gr 1:1.25-2.5*ULN;Gr 2: 2.6-5*ULN;Gr 3:5.1-10*ULN;Gr4:>10*ULN.ALT/SGPT (U/L)Gr 1:1.25-2.5*ULN;Gr 2:1.4-2.09*ULN;Gr 3:5.1-10*ULN;Gr4:>10*ULN. Lipase(U/L)Gr 1:1.1-1.39*ULN;Gr 2:>1.5-2*ULN;Gr 3:2.5-5;Gr 4:5*ULN.Proteinuria(g/24 hr loss)Gr 1:1+or <1;Gr 2:2-3+or>1-2; Gr 3:4+or>2-3.5;Gr4:>3.5.Creatine kinase(IU/L)Gr1:2-3*ULN;Gr 2:3.1-5*ULN;Gr 3:5.1-10*ULN;Gr4:>10*ULN.	While on treatment from Baseline through Week 96	Yes

External Links

•   BMS Clinical Trials Disclosure
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