DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection

Information source: ViiV Healthcare
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Infection, Human Immunodeficiency Virus I; HIV Infection

Intervention: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r) (Drug); Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: ViiV Healthcare

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: ViiV Healthcare

Summary

This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative subjects. All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.

Clinical Details

Official title: See Detailed Description

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

Primary outcome: Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit

Secondary outcome:

Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase

Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit

Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit

Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit

Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit

Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit

Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit

Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36

Number of Participants Who Met the PDVF Criteria at Week 84

Number of Participants Who Met the PDVF Criteria at Week 144

Change From Baseline in HIV-1 RNA at Week 36

Change From Baseline in HIV-1 RNA at Week 84

Change From Baseline in HIV-1 RNA at Week 144

Change From Baseline in CD4+ Cell Count at Week 36

Change From Baseline in CD4+ Cell Count at Week 84

Change From Baseline in CD4+ Cell Count at Week 144

Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36

Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84

Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144

Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir

Mean Percent Compliance at Week 36

Mean Percent Compliance at Week 84

Mean Percent Compliance at Week 144

Detailed description: Safety and Efficacy of an Initial Regimen of Atazanavir (ATV) + Ritonavir (/r) + the Abacavir/Lamivudine Fixed-Dose Combination Tablet (ABC/3TC FDC) for 36 weeks followed by Simplification to Atazanavir with ABC/3TC FDC or Maintenance of the Initial Regimen for an Additional 48 weeks in Antiretroviral-Naive HIV-1 Infected HLA-B*5701 Negative Subjects followed by an Optional 60-Week Treatment Extension Phase

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria:

- Subject is ≥ 18 years of age and has documented evidence of HIV-1 infection. (A

female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)

- Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any

NRTI and no prior therapy with either a PI or NNRTI).

- Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL by Roche COBAS AMPLICOR™ (Version 1. 5)

method at screening (if no other documentation of HIV infection is available, a positive result here may serve as documentation of HIV infection for this study).

- Subject is willing and able to understand and provide written informed consent prior

to participation in this study. Exclusion criteria:

- Subject is HLA-B*5701 positive.

- Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at

screening (+ HbsAg)

- Genotyping results performed at the screening indicate that the subject has any of

the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90.

- Women who are pregnant or breastfeeding.

- Subject has an active or acute CDC Clinical Category C event at screening. Treatment

for the acute event must have been completed at least 30 days prior to screening.

- Subject is, in the opinion of the investigator, unable to complete the 84-week dosing

period and protocol evaluations and assessments.

- Subject has ongoing clinically relevant pancreatitis or clinically relevant hepatitis

at screening.

- Presence of a newly diagnosed HIV-related opportunistic infection or any medical

condition requiring acute therapy at the time of enrollment.

- Subject suffers from a serious medical condition, such as diabetes, congestive heart

failure, cardiomyopathy or other cardiac dysfunction (including known, clinically significant cardiac conduction system disease, severe first degree atrioventricular block [PR interval > 0. 26 seconds], second or third-degree atrioventricular block), which in the opinion of the investigator would compromise the safety of the subject.

- Subject has pre-existing mental, physical, or substance abuse disorder, which in the

opinion of the investigator would interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.

- Subject has a history of inflammatory bowel disease or malignancy, intestinal

ischemia, malabsorption, or other gastrointestinal dysfunction, which may interfere with drug absorption or render the subject unable to take oral medication.

- Subject requires treatment with foscarnet, hydroxyurea or other agents with

documented activity against HIV-1 in vitro within 28 days of study administration.

- Subject requires treatment with immunomodulating agents (such as systemic

corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to screening, or subject had received an HIV-1 immunotherapeutic vaccine within 90 days prior to screening. Subjects using inhaled corticosteroids are eligible for enrollment.

- Creatinine clearance <50 mL/min via the Cockroft-Gault method [Cockroft, 1976].

- Active alcohol or substance use sufficient, in the investigator's opinion, to prevent

adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis.

- Hypersensitivity to any component of the study drugs.

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper

limit of normal (ULN).

- Total bilirubin > 1. 5 times the upper limit of normal (ULN).

- Subject has any acute laboratory abnormality at screening, which, in the opinion of

the investigator, would preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality would exclude a subject from study participation.

- Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic

agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.

- Enrolled in one or more investigational drug protocols, which may have impacted HIV-1

RNA suppression.

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for

treatment of either a psychiatric or physical (e. g., infectious disease) illness must not be enrolled into this study.

- Subjects requiring concomitant administration of proton pump inhibitors.

- Subjects who require treatment with the prohibited medications within 28 days of

commencement of investigational product, or an anticipated need during the study. Eligibility Criteria for Treatment Extension Phase:

- Subjects will be eligible to continue in the treatment extension phase (Weeks 84 to 144)

if they have successfully completed the 84-week study.

Locations and Contacts

GSK Investigational Site, Ponce 00717, Puerto Rico

GSK Investigational Site, Ponce 00731, Puerto Rico

GSK Investigational Site, San Juan 00909-1711, Puerto Rico

GSK Investigational Site, San Juan 00910, Puerto Rico

GSK Investigational Site, Phoenix, Arizona 85012, United States

GSK Investigational Site, Long Beach, California 90813, United States

GSK Investigational Site, Los Angeles, California 90022, United States

GSK Investigational Site, Los Angeles, California 90033, United States

GSK Investigational Site, Newport Beach, California 92663, United States

GSK Investigational Site, Oakland, California 94609, United States

GSK Investigational Site, Denver, Colorado 80220, United States

GSK Investigational Site, Glastonbury, Connecticut 06033, United States

GSK Investigational Site, Washington, District of Columbia 20007, United States

GSK Investigational Site, Washington, District of Columbia 20009, United States

GSK Investigational Site, Washington, District of Columbia 20036, United States

GSK Investigational Site, Washington, District of Columbia 20037, United States

GSK Investigational Site, Fort Lauderdale, Florida 33308, United States

GSK Investigational Site, Fort Lauderdale, Florida 33316, United States

GSK Investigational Site, Fort Pierce, Florida 34982, United States

GSK Investigational Site, Ft. Lauderdale, Florida 33306, United States

GSK Investigational Site, Miami, Florida 33136, United States

GSK Investigational Site, Orlando, Florida 32803, United States

GSK Investigational Site, Plantation, Florida 33317, United States

GSK Investigational Site, Sarasota, Florida 34243, United States

GSK Investigational Site, Tampa, Florida 33607, United States

GSK Investigational Site, Tampa, Florida 33602, United States

GSK Investigational Site, Atlanta, Georgia 30308, United States

GSK Investigational Site, Atlanta, Georgia 30309, United States

GSK Investigational Site, Atlanta, Georgia 30339, United States

GSK Investigational Site, Augusta, Georgia 30912, United States

GSK Investigational Site, Decatur, Georgia 30033, United States

GSK Investigational Site, Chicago, Illinois 60637, United States

GSK Investigational Site, Chicago, Illinois 60657, United States

GSK Investigational Site, Maywood, Illinois 60153, United States

GSK Investigational Site, Lexington, Kentucky 40536, United States

GSK Investigational Site, Baltimore, Maryland 21201, United States

GSK Investigational Site, Boston, Massachusetts 02115, United States

GSK Investigational Site, Boston, Massachusetts 02215, United States

GSK Investigational Site, Detroit, Michigan 48202, United States

GSK Investigational Site, Minneapolis, Minnesota 55404, United States

GSK Investigational Site, Minneapolis, Minnesota 55415, United States

GSK Investigational Site, St. Louis, Missouri 63110, United States

GSK Investigational Site, Hillsborough, New Jersey 08844, United States

GSK Investigational Site, Newark, New Jersey 07102, United States

GSK Investigational Site, Somers Point, New Jersey 08244, United States

GSK Investigational Site, New York, New York 10011, United States

GSK Investigational Site, Valhalla, New York 10595, United States

GSK Investigational Site, Charlotte, North Carolina 28209, United States

GSK Investigational Site, Greenville, North Carolina 27834, United States

GSK Investigational Site, Akron, Ohio 44304, United States

GSK Investigational Site, Toledo, Ohio 43614, United States

GSK Investigational Site, Toronto, Ontario M4N 3M5, Canada

GSK Investigational Site, Toronto, Ontario M5B 1L6, Canada

GSK Investigational Site, Toronto, Ontario M5G 2N2, Canada

GSK Investigational Site, Philadelphia, Pennsylvania 19104, United States

GSK Investigational Site, Philadelphia, Pennsylvania 19107, United States

GSK Investigational Site, Montreal, Quebec H2L 4P9, Canada

GSK Investigational Site, Montreal, Quebec H2L 5B1, Canada

GSK Investigational Site, Montreal, Quebec H2X 2P4, Canada

GSK Investigational Site, Providence, Rhode Island 2906, United States

GSK Investigational Site, Austin, Texas 78705, United States

GSK Investigational Site, Dallas, Texas 75246, United States

GSK Investigational Site, Dallas, Texas 75204, United States

GSK Investigational Site, El Paso, Texas 79925, United States

GSK Investigational Site, Fort Worth, Texas 76104, United States

GSK Investigational Site, Galveston, Texas 77555, United States

GSK Investigational Site, Houston, Texas 77004, United States

GSK Investigational Site, Houston, Texas 77030, United States

GSK Investigational Site, Houston, Texas 77057, United States

GSK Investigational Site, Longview, Texas 75605, United States

GSK Investigational Site, Annandale, Virginia 22003, United States

GSK Investigational Site, Norfolk, Virginia 23507, United States

Additional Information

Related publications:

L Ross, E Dejesus, M Potter, A LaMarca, D Murphy, I Melendez-Rivera, D Ward, P Wannamaker, J Uy, L Patel, H Amrine-Madsen, J Horton. Epidemiological and Genotypic Clustering of HIV infection within North America During 2007 International HIV & Hepatitis Drug Resistance Workshop & Curative Strategies, 8-12 June 2010, Dubrovnik, Croatia, Poster 150.

Young B, Squires K, Patel P, Dejesus E, Bellos N, Berger D, Sutherland-Phillips DH, Liao Q, Shaefer M, Wannamaker P. First large, multicenter, open-label study utilizing HLA-B*5701 screening for abacavir hypersensitivity in North America. AIDS. 2008 Aug 20;22(13):1673-5. doi: 10.1097/QAD.0b013e32830719aa.

• L Ross, K Squires, B Young, E DeJesus, N Bellos, D Murphy, A Rachlis, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Genotypic Screening Impact in ARIES [Atazanavir (ATV) + Ritonavir (/r) + Abacavir/Lamivudine (ABC/3TC) for 36 Weeks Followed By Randomization to ATV +ABC/3TC or ATV/r + ABC/3TC for 48 Wks in HIV-infected, ART Naïve Patients] :Low Rates of Virologic Failure. The 19th Annual Canadian Conference on HIV/AIDS Research, 13-16 May 2010, Saskatoon, Canada. Poster P-169.

K Squires, E DeJesus, N Bellos, D Ward, D Murphy, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Sustained Virologic Efficacy of Atazanavir (ATV) Versus Atazanavir/Ritonavir (ATV/r), each in Combination with Abacavir/Lamivudine (ABC/3TC) over 120 Weeks: the ARIES Trial. 48th ICAAC; September 12-15, 2010, Boston, MA. Poster H-204.

K Squires, B Young, E DeJesus, N Bellos, D Murphy, D Sutherland-Phillips, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Atazanavir/Ritonavir (ATV/r) + Abacavir/Lamivudine (ABC/3TC) in Antiretroviral (ART)-Naive HIV-1 Infected HLA-B*5701 Negative Subjects Demonstrates Efficacy and Safety: the ARIES Trial. 48th ICAAC; October 25-28, 2008, Washington, DC. Poster H-1250a.

K Squires, B Young, E DeJesus, N Bellos, D Murphy, D Sutherland-Phillips, H Zhao, L Patel, L Ross, P Wannamaker, M Shaefer. Similar Efficacy and Tolerability of Atazanavir (ATV) Compared to ATV/Ritonavir (RTV, r), Each in Combination with Abacavir/Lamivudine (ABC/3TC), after Initial Suppression with ABC/3TC + ATV/r in HIV-1 Infected Patients: 84 Week Results of the ARIES Trial. 5th IAS Conference; Cape Town, South Africa. Abstract WELBB103

Squires KE, Young B, DeJesus E, Bellos N, Murphy D, Sutherland-Phillips DH, Zhao HH, Patel LG, Ross LL, Wannamaker PG, Shaefer MS; ARIES Study Team. Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and ritonavir-boosted atazanavir in HIV-infected patients. HIV Clin Trials. 2010 Mar-Apr;11(2):69-79. doi: 10.1310/hct1102-69.

Squires KE, Young B, Dejesus E, Bellos N, Murphy D, Zhao HH, Patel LG, Ross LL, Wannamaker PG, Shaefer MS; ARIES study team. Similar efficacy and tolerability of atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine after initial suppression with abacavir/lamivudine plus ritonavir-boosted atazanavir in HIV-infected patients. AIDS. 2010 Aug 24;24(13):2019-27. doi: 10.1097/QAD.0b013e32833bee1b.

Starting date: March 2007
Last updated: March 15, 2012

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017