BMS-Reyataz Study in Treatment in Naive Subjects to Compare the Efficacy and Safety Between Boosted Reyataz and Kaletra When in Combination With Fixed Dose Truvada

NCT ID: NCT00272779

Last Updated: 2011-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1057 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2008-10-31

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and antiviral effects of atazanavir (ATV) plus ritonavir (RTV) versus a combination drug of lopinavir (LPV) plus RTV. A combination drug containing tenofovir (TDF) and emtricitabine (FTC) will also be taken by participants in both arms.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atazanavir (ATV) + Ritonovir (RTV)

Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.

Group Type: ACTIVE_COMPARATOR

ATV

Intervention Type: DRUG

300mg Oral capsules for 96 weeks

RTV

Intervention Type: DRUG

100mg Oral Capsules for 96 weeks

Tenofovi-Emtricitabine (TDF/FTC) tablet

Intervention Type: DRUG

One tablet with 300 mg - 200 mg once a day for 96 weeks.

Lopinavir (LPV) + RTV

Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.

Group Type: ACTIVE_COMPARATOR

RTV

Intervention Type: DRUG

100mg Oral Capsules for 96 weeks

Tenofovi-Emtricitabine (TDF/FTC) tablet

Intervention Type: DRUG

One tablet with 300 mg - 200 mg once a day for 96 weeks.

LPV

Intervention Type: DRUG

400 mg (3 133mg capsules) BID for 96 weeks

Interventions

ATV

300mg Oral capsules for 96 weeks

Intervention Type: DRUG

RTV

100mg Oral Capsules for 96 weeks

Intervention Type: DRUG

Tenofovi-Emtricitabine (TDF/FTC) tablet

One tablet with 300 mg - 200 mg once a day for 96 weeks.

Intervention Type: DRUG

LPV

400 mg (3 133mg capsules) BID for 96 weeks

Intervention Type: DRUG

Other Intervention Names

Atazanavir; Reyataz; BMS-232632

Eligibility Criteria

Inclusion Criteria

• HIV RNA ≥5000 c/ml

Exclusion Criteria

• Any antiretroviral therapy within 30 days prior to screening;
• Women of Childbearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the study;
• WOCBP using a prohibited contraceptive method
• WOCBP who are pregnant or breastfeeding;
• Women with a positive pregnancy test on enrollment or prior to study drug administration;
• Presence of a newly diagnosed HIV-Related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment;
• Suspected primary (acute) HIV infection;
• Prior antiviral therapy (>30 days of NRTI and/or >7 days of non-nucleoside reverse transcriptase inhibitor (NNRTI) or PI therapies) or any antiretroviral therapy within 30 days prior to screening; some exceptions are allowed for ARV therapy in use for Mother-to-child transmission;
• Participants with Cushing's syndrome;
• Untreated hypothyroidism or hyperthyroidism. A participant who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the thyroid stimulating hormone (TSH) performed within 30 days of screening is within normal drug range;
• Recent therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start or expected need for such therapy at the time of enrollment; or therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect CYP3A4;
• Participants with obstructive liver disease;
• 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;
• Proven or suspected acute hepatitis in the 30 days prior to study entry;
• Intractable diarrhea (≥6 loose stools/day for at least 7 consecutive days) within 30 days prior to study entry;
• Inability to swallow capsules;
• Active peripheral neuropathy;
• Presence of cardiomyopathy (due to any cause) or any significant cardiovascular disease, such as unstable ischemic heart disease;
• Known, clinically significant cardiac conduction system disease.
• Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:

1. calculated creatine clearance <60 mL/min as estimated by the Cockcroft-Gault equation;

2. total serum lipase ≥ 1.4 times the upper limit of normal;

3. liver enzymes (AST, ALT) ≥ 5 times the upper limit of normal;

4. total serum bilirubin ≥ 1.5 times the upper limit of normal.

• Hypersensitivity to any component of the formulation of study drug;
• Prohibited therapies;
• Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for study or unable to comply with the dosing requirements;
• Prisoners or participants 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Bristol-Myers Squibb

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution

Phoenix, Arizona, United States

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Laguna Beach, California, United States

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Washington D.C., District of Columbia, United States

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Fort Lauderdale, Florida, United States

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Orlando, Florida, United States

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Huntersville, North Carolina, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Capital Federal, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Darlinghurst, New South Wales, Australia

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Carlton, Victoria, Australia

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South Yarra, Victoria, Australia

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Vienna, , Austria

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Bruges, , Belgium

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Ghent, , Belgium

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Curitiba, Paraná, Brazil

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Recife, Pernambuco, Brazil

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Campinas, São Paulo, Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Viña del Mar, Región de Valparaíso, Chile

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Santiago, Santiago Metropolitan, Chile

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Bogotá, , Colombia

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San José, , Costa Rica

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Santo Domingo, , Dominican Republic

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Nice, , France

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Paris, , France

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Villejuif, , France

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Berlin, , Germany

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Bonn, , Germany

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Cologne, , Germany

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Hamburg, , Germany

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Guatemala City, , Guatemala

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Kowloon, , Hong Kong

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Jakarta, , Indonesia

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Genova, , Italy

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Milan, , Italy

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Roma, , Italy

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Torino, , Italy

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Guadalajara, Jalisco, Mexico

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Zapopal, Jalisco, Mexico

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Zapopan, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Chihuaha, , Mexico

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Durango, , Mexico

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San Luis Potisi, , Mexico

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Maastricht, , Netherlands

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Utrecht, , Netherlands

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Panama City, , Panama

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Lima, , Peru

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Lisbon, , Portugal

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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Singapore, , Singapore

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Port Elizabeth, Eastern Cape, South Africa

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Bloemfontein, Free State, South Africa

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Johannesburg, Gauteng, South Africa

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Meadowdale, Gauteng, South Africa

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Westdene, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Mowbray, Western Cape, South Africa

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Parow, Western Cape, South Africa

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Rugby, Western Cape, South Africa

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Barcelona, , Spain

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Córdoba, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Kaohsiung City, , Taiwan

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Taipei, , Taiwan

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Chiang Mai, , Thailand

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Khonkaen, , Thailand

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London, Greater London, United Kingdom

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Manchester, Greater Manchester, United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; Colombia; Costa Rica; Dominican Republic; France; Germany; Guatemala; Hong Kong; Indonesia; Italy; Mexico; Netherlands; Panama; Peru; Portugal; Puerto Rico; Singapore; South Africa; Spain; Taiwan; Thailand; United Kingdom

References

Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Wirtz V, Lataillade M, Absalon J, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32. doi: 10.1097/QAI.0b013e3181c990bf.

Reference Type: BACKGROUND

PMID: 20032785 (View on PubMed)

Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. doi: 10.1016/S0140-6736(08)61081-8.

Reference Type: BACKGROUND

PMID: 18722869 (View on PubMed)

Zhu L, Liao S, Child M, Zhang J, Persson A, Sevinsky H, Eley T, Xu X, Krystal M, Farajallah A, McGrath D, Molina JM, Bertz R. Pharmacokinetics and inhibitory quotient of atazanavir/ritonavir versus lopinavir/ritonavir in HIV-infected, treatment-naive patients who participated in the CASTLE Study. J Antimicrob Chemother. 2012 Feb;67(2):465-8. doi: 10.1093/jac/dkr490. Epub 2011 Nov 25.

Reference Type: DERIVED

PMID: 22121190 (View on PubMed)

Uy J, Yang R, Wirtz V, Sheppard L, Farajallah A, McGrath D. Treatment of advanced HIV disease in antiretroviral-naive HIV-1-infected patients receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir, each in combination with tenofovir disoproxil fumarate and emtricitabine. AIDS Care. 2011 Nov;23(11):1500-4. doi: 10.1080/09540121.2011.565033. Epub 2011 Jul 7.

Reference Type: DERIVED

PMID: 21732894 (View on PubMed)

Squires KE, Johnson M, Yang R, Uy J, Sheppard L, Absalon J, McGrath D. Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J Antimicrob Chemother. 2011 Feb;66(2):363-70. doi: 10.1093/jac/dkq457. Epub 2010 Dec 9.

Reference Type: DERIVED

PMID: 21148235 (View on PubMed)

Other Identifiers

AI424-138

Identifier Type: -

Identifier Source: org_study_id