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Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine

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

Condition(s) targeted: HIV-1

Intervention: Maraviroc + Zidovudine/Lamivudine (Drug); Efavirenz + Zidovudine/Lamivudine (Drug); Maraviroc (UK-427,857) + Zidovudine/Lamivudine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: ViiV Healthcare

Official(s) and/or principal investigator(s):
Pfizer CT.gov Call Center, Study Director, Affiliation: Pfizer

Summary

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1. 6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.

Clinical Details

Official title: A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population

Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population

Secondary outcome:

Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression

Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression

Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96

Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels

Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96

Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96

Time to Virologic Failure

Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48

Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96

Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96

Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening

Eligibility

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Men or women at least 16 years of age (or minimum age as determined by local

regulatory authorities)

- HIV-1 RNA viral load of greater than or equal to 2, 000 copies/mL

- A negative urine pregnancy test at the baseline visit for Women of Child Bearing

Potential (WOCBP)

- Effective barrier contraception for WOCBP and males

Exclusion Criteria:

- Suspected or documented active, untreated HIV-1 related opportunistic infection (OI)

or other condition requiring acute therapy

- Treatment for an active opportunistic infection, or unexplained temperature >38. 5

degrees Celsius for 7 consecutive days

- Prior treatment with efavirenz, zidovudine or lamivudine or with any other

antiretroviral therapy for more than 14 days at any time

- Active alcohol or substance abuse sufficient, in the Investigator's judgment, to

prevent adherence to study medication and/or follow up

- Lactating women, or planned pregnancy during the trial period

- Suspected primary (acute) HIV-1 infection

- Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or

cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period

- Documented or suspected acute hepatitis or pancreatitis within 30 days prior to

randomization

- Significantly elevated liver enzymes or cirrhosis

- Significant neutropenia, anemia or thrombocytopenia

- Malabsorption or an inability to tolerate oral medications

- Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease

- Certain medications

- Genotypic or phenotypic resistance to efavirenz, zidovudine or lamivudine

- X4- or dual/mixed-tropic virus or repeated assay failure

- Any other clinical condition that, in the Investigator's judgement, would potentially

compromise study compliance or the ability to evaluate safety/efficacy

Locations and Contacts

Pfizer Investigational Site, Buenos Aires, Argentina

Pfizer Investigational Site, Ciudad de Buenos Aires C1202ABB, Argentina

Pfizer Investigational Site, Ciudad de Buenos Aires C1406FWY, Argentina

Pfizer Investigational Site, Ciudad de Buenos C1282AEN, Argentina

Pfizer Investigational Site, Provincia de Buenos Aires, Argentina

Pfizer Investigational Site, Provincia de Santa Fe, Argentina

Pfizer Investigational Site, Brussels 1000, Belgium

Pfizer Investigational Site, Brussels 1200, Belgium

Pfizer Investigational Site, Gent 9000, Belgium

Pfizer Investigational Site, Leuven B-3000 Leuven, Belgium

Pfizer Investigational Site, Antella (FI) 50011, Italy

Pfizer Investigational Site, Brescia 25123, Italy

Pfizer Investigational Site, Milano 20127, Italy

Pfizer Investigational Site, Modena 41100, Italy

Pfizer Investigational Site, Roma 00161, Italy

Pfizer Investigational Site, Roma 00185, Italy

Pfizer Investigational Site, Torino 10149, Italy

Pfizer Investigational Site, Amsterdam 1091 AC, Netherlands

Pfizer Investigational Site, Rotterdam 3015 GD, Netherlands

Pfizer Investigational Site, Utrecht 3584 CX, Netherlands

Pfizer Investigational Site, Bialystok 15-540, Poland

Pfizer Investigational Site, Bydgoszcz 85-030, Poland

Pfizer Investigational Site, Chorzow 41-500, Poland

Pfizer Investigational Site, Gdansk 80-214, Poland

Pfizer Investigational Site, Krakow 31-531, Poland

Pfizer Investigational Site, Szczecin 71-455, Poland

Pfizer Investigational Site, Warszawa 01-201, Poland

Pfizer Investigational Site, Ponce 00731, Puerto Rico

Pfizer Investigational Site, Rio Piedras 00935, Puerto Rico

Pfizer Investigational Site, San Juan 00909, Puerto Rico

Pfizer Investigational Site, San Juan 00935, Puerto Rico

Pfizer Investigational Site, Bloomfontein, South Africa

Pfizer Investigational Site, Cape Town 7780, South Africa

Pfizer Investigational Site, Cape Town 7550, South Africa

Pfizer Investigational Site, Cape Town 7705, South Africa

Pfizer Investigational Site, Cape Town 7405, South Africa

Pfizer Investigational Site, Johannesburg 2047, South Africa

Pfizer Investigational Site, Pretoria North 0182, South Africa

Pfizer Investigational Site, Pretoria 0132, South Africa

Pfizer Investigational Site, Soweto, Johannesburg 2013, South Africa

Pfizer Investigational Site, Basel 4031, Switzerland

Pfizer Investigational Site, Bern 3010, Switzerland

Pfizer Investigational Site, Genève 1211, Switzerland

Pfizer Investigational Site, Lugano 6900, Switzerland

Pfizer Investigational Site, St. Gallen 9007, Switzerland

Pfizer Investigational Site, Zürich 8038, Switzerland

Pfizer Investigational Site, Zürich 8091, Switzerland

Pfizer Investigational Site, Birmingham B9 5SS, United Kingdom

Pfizer Investigational Site, Brighton BN2 1ES, United Kingdom

Pfizer Investigational Site, Edinburgh EH4 2XU, United Kingdom

Pfizer Investigational Site, London NW3 2QG, United Kingdom

Pfizer Investigational Site, London SE5 9RS, United Kingdom

Pfizer Investigational Site, London SW10 9NH, United Kingdom

Pfizer Investigational Site, London W2 1NY, United Kingdom

Pfizer Investigational Site, Manchester M8 5RB, United Kingdom

Pfizer Investigational Site, Birmingham, Alabama 35233, United States

Pfizer Investigational Site, Birmingham, Alabama 35294-2050, United States

Pfizer Investigational Site, Calgary, Alberta T2R0X7, Canada

Pfizer Investigational Site, Edmonton, Alberta T6G 2B7, Canada

Pfizer Investigational Site, Edmonton, Alberta T6G 2C8, Canada

Pfizer Investigational Site, Vancouver, British Columbia V6Z 2C7, Canada

Pfizer Investigational Site, Vancouver, British Columbia V6Z 1Y6, Canada

Pfizer Investigational Site, Vancouver, British Columbia V6Z 2T1, Canada

Pfizer Investigational Site, Vancouver, British Columbia V6B 1R3, Canada

Pfizer Investigational Site, Beverly Hills, California 90211, United States

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

Pfizer Investigational Site, Los Angeles, California 90048, United States

Pfizer Investigational Site, Los Angeles, California 90069, United States

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

Pfizer Investigational Site, Oakland, California 94602, United States

Pfizer Investigational Site, Sacramento, California 95825, United States

Pfizer Investigational Site, San Francisco, California 94115, United States

Pfizer Investigational Site, San Francisco, California 94115-3029, United States

Pfizer Investigational Site, Aurora, Colorado 80045, United States

Pfizer Investigational Site, Port Elizabeth, Eastern Cape 6065, South Africa

Pfizer Investigational Site, Jacksonville, Florida 32209, United States

Pfizer Investigational Site, Miami Beach, Florida 33139, United States

Pfizer Investigational Site, Miami, Florida 33133, United States

Pfizer Investigational Site, Miami, Florida 33136, United States

Pfizer Investigational Site, Orlando, Florida 32803, United States

Pfizer Investigational Site, Sarasota, Florida 34243, United States

Pfizer Investigational Site, Tampa, Florida 33614, United States

Pfizer Investigational Site, Bloemfontein, Free State 9300, South Africa

Pfizer Investigational Site, Johannesburg, Gauteng 2092, South Africa

Pfizer Investigational Site, Pretoria, Gauteng 0083, South Africa

Pfizer Investigational Site, Atlanta, Georgia 30308, United States

Pfizer Investigational Site, Chicago, Illinois 60611, United States

Pfizer Investigational Site, Indianapolis, Indiana 46202, United States

Pfizer Investigational Site, Dundee, KwaZulu Natal 3000, South Africa

Pfizer Investigational Site, Edinburgh, Loth ED4 2XU, United Kingdom

Pfizer Investigational Site, Winnipeg, Manitoba R3A 1R9, Canada

Pfizer Investigational Site, Baltimore, Maryland 21201, United States

Pfizer Investigational Site, Boston, Massachusetts 02118-2393, United States

Pfizer Investigational Site, Boston, Massachusetts 02111, United States

Pfizer Investigational Site, Boston, Massachusetts 02215, United States

Pfizer Investigational Site, Springfield, Massachusetts 01107, United States

Pfizer Investigational Site, Del. Tlalpan C.P., Mexico City 14050, Mexico

Pfizer Investigational Site, Del. Tlalpan, C.P., Mexico D.F. 14080, Mexico

Pfizer Investigational Site, Del. Tlalpan, C.P., Mexico D.F. 14000, Mexico

Pfizer Investigational Site, Delegacion Tlalpan C. P, Mexico D.F. 14080, Mexico

Pfizer Investigational Site, Omaha, Nebraska 68106, United States

Pfizer Investigational Site, Burwood, New South Wales 2134, Australia

Pfizer Investigational Site, Darlinghurst, New South Wales 2010, Australia

Pfizer Investigational Site, Surrey Hills, New South Wales 2010, Australia

Pfizer Investigational Site, Wentworthville, New South Wales 2145, Australia

Pfizer Investigational Site, Albany, New York 12208, United States

Pfizer Investigational Site, Brooklyn, New York 11203, United States

Pfizer Investigational Site, Flushing, New York 11355, United States

Pfizer Investigational Site, Manhasset, New York 11030, United States

Pfizer Investigational Site, New York, New York 10016, United States

Pfizer Investigational Site, Huntersville, North Carolina 28078, United States

Pfizer Investigational Site, Halifax, Nova Scotia B3H 1V7, Canada

Pfizer Investigational Site, Cincinnati, Ohio 45267-0405, United States

Pfizer Investigational Site, Oklahoma City, Oklahoma 73104-5068, United States

Pfizer Investigational Site, Oklahoma City, Oklahoma 73104, United States

Pfizer Investigational Site, Hamilton, Ontario L8N 3Z5, Canada

Pfizer Investigational Site, Ottawa, Ontario K1H 8L6, Canada

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

Pfizer Investigational Site, Toronto, Ontario M5B 1W8, Canada

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

Pfizer Investigational Site, Philadelphia, Pennsylvania 19104, United States

Pfizer Investigational Site, El Palomar, Provincia de Buenos Aires 1684, Argentina

Pfizer Investigational Site, Neuquen, Provincia de Neuquen Q8300PMB, Argentina

Pfizer Investigational Site, Montreal, Quebec H2W 1T8, Canada

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

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

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

Pfizer Investigational Site, Montreal, Quebec H3G 1A4, Canada

Pfizer Investigational Site, Montreal, Quebec H2L 4M1, Canada

Pfizer Investigational Site, Sainte-Foy, Quebec G1V 4G2, Canada

Pfizer Investigational Site, Herston, Queensland 4029, Australia

Pfizer Investigational Site, Miami, Queensland 4220, Australia

Pfizer Investigational Site, Rio de Janeiro, RJ 20210-030, Brazil

Pfizer Investigational Site, Columbia, South Carolina 29206, United States

Pfizer Investigational Site, Dallas, Texas 75208, United States

Pfizer Investigational Site, Dallas, Texas 75246, United States

Pfizer Investigational Site, Houston, Texas 77006, United States

Pfizer Investigational Site, Houston, Texas 77098, United States

Pfizer Investigational Site, Melbourne, Victoria 3004, Australia

Pfizer Investigational Site, North Fitzroy, Victoria 3068, Australia

Pfizer Investigational Site, South Yarra, Victoria 3141, Australia

Pfizer Investigational Site, Annandale, Virginia 22003, United States

Pfizer Investigational Site, Puyallup, Washington 98372, United States

Pfizer Investigational Site, Tacoma, Washington 98405, United States

Additional Information

To obtain contact information for a study center near you, click here.

Starting date: November 2004
Last updated: August 7, 2013

Page last updated: August 23, 2015

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