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Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine (MERIT)
This study is ongoing, but not recruiting participants.
First Received: December 6, 2004   Last Updated: November 12, 2009   History of Changes
Sponsor: Pfizer
Information provided by: Pfizer
ClinicalTrials.gov Identifier: NCT00098293
  Purpose

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.


Condition Intervention Phase
HIV-1
Drug: Maraviroc + Zidovudine/Lamivudine
Drug: Efavirenz + Zidovudine/Lamivudine
Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine
Phase II
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of patients with undetectable viral load at 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the time to loss of virological response through Weeks 48 and 96 for the UK-427,857 regimen versus the efavirenz regimen. [ Time Frame: week 48 and 96 ] [ Designated as safety issue: No ]
  • To compare the reduction of plasma log10 HIV-1 RNA from baseline through Weeks 24, 48 and 96 for the UK-427,857 regimen versus the efavirenz regimen. [ Time Frame: week 24, 48 and 96 ] [ Designated as safety issue: No ]
  • To compare the differences in the magnitude of changes in CD4 cell counts from baseline through Weeks 24, 48 and 96 for the UK-427,857 versus the efavirenz regimen [ Time Frame: week 24, 48 and 96 ] [ Designated as safety issue: No ]
  • To compare the differences in the magnitude of changes in CD8 cell counts from baseline through Weeks 24, 48 and 96 for the UK-427,857 regimens versus the efavirenz regimen. [ Time Frame: week 24, 48 and 96 ] [ Designated as safety issue: No ]
  • To compare the Time-Averaged Difference (TAD) in log10 HIV-1 RNA at Weeks 24, 48 and 96 for the UK-427,857 regimen versus the efavirenz regimen. [ Time Frame: week 24, 48 and 96 ] [ Designated as safety issue: No ]
  • To assess HIV-1 genotype and phenotype at baseline and at the time of failure [ Time Frame: baseline and at the time of failure ] [ Designated as safety issue: No ]
  • To assess HIV-1 tropism at baseline and at the time of failure [ Time Frame: baseline and at the time of failure ] [ Designated as safety issue: No ]
  • To assess the association between baseline resistance and virological response. [ Time Frame: baseline resistance and virological response. ] [ Designated as safety issue: No ]
  • To compare the safety and tolerability of the two UK-427,857 regimens versus the efavirenz regimen. [ Time Frame: duration of trial ] [ Designated as safety issue: Yes ]
  • To assess whether the percentage of subjects with HIV 1 RNA less than 400 or 50 copies per mL at Weeks 24 and 96 for the UK 427,857 regimen is noninferior versus the efavirenz regimen each in combination with zidovudine/lamivudine. [ Time Frame: week 24 and 96 ] [ Designated as safety issue: No ]

Enrollment: 898
Study Start Date: November 2004
Estimated Study Completion Date: June 2011
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: Maraviroc + Zidovudine/Lamivudine
maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
3: Active Comparator Drug: Efavirenz + Zidovudine/Lamivudine
efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
2: Experimental
Following a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz
Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine
maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098293

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Locations
United States, Alabama
Pfizer Investigational Site
Birmingham, Alabama, United States, 35233
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Birmingham, Alabama, United States, 35294-2050
United States, California
Pfizer Investigational Site
Beverly Hills, California, United States, 90211
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Los Angeles, California, United States, 90069
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Oakland, California, United States, 94602
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Los Angeles, California, United States, 90048
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Los Angeles, California, United States, 90022
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Newport Beach, California, United States, 92663
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Los Angeles, California, United States, 90048
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Sacramento, California, United States, 95825
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San Francisco, California, United States, 94115
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San Francisco, California, United States, 94115-3029
United States, Colorado
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Denver, Colorado, United States, 80262
United States, Florida
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Jacksonville, Florida, United States, 32209
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Orlando, Florida, United States, 32803
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Miami, Florida, United States, 33136
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Miami Beach, Florida, United States, 33139
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Miami, Florida, United States, 33133
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Sarasota, Florida, United States, 34243
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Tampa, Florida, United States, 33614
United States, Georgia
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Atlanta, Georgia, United States, 30308
United States, Illinois
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Chicago, Illinois, United States, 60611
United States, Indiana
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Indianapolis, Indiana, United States, 46202
United States, Maryland
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Baltimore, Maryland, United States, 21201
United States, Massachusetts
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Boston, Massachusetts, United States, 02215
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Boston, Massachusetts, United States, 02111
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Boston, Massachusetts, United States, 02118-2393
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Springfield, Massachusetts, United States, 01107
United States, Nebraska
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Omaha, Nebraska, United States, 68106
United States, New York
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Albany, New York, United States, 12208
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Brooklyn, New York, United States, 11203
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Flushing, New York, United States, 11355
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Manhasset, New York, United States, 11030
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New York, New York, United States, 10016
United States, North Carolina
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Huntersville, North Carolina, United States, 28078
United States, Ohio
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Cincinnati, Ohio, United States, 45267-0405
United States, Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
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Oklahoma City, Oklahoma, United States, 73104-5068
United States, Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
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Columbia, South Carolina, United States, 29206
United States, Texas
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Dallas, Texas, United States, 75246
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Dallas, Texas, United States, 75208
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Houston, Texas, United States, 77006
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Houston, Texas, United States, 77098
United States, Virginia
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Annandale, Virginia, United States, 22003
United States, Washington
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Puyallup, Washington, United States, 98372
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Tacoma, Washington, United States, 98405
Argentina
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Buenos Aires, Argentina
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Ciudad de Buenos, Argentina, C1282AEN
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Ciudad de Buenos Aires, Argentina, C1202ABB
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Ciudad de Buenos Aires, Argentina, C1406FWY
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Ciudad de Buenos Aires, Argentina
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Provincia de Buenos Aires, Argentina
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Provincia de Santa Fe, Argentina
Argentina, Provincia de Buenos Aires
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El Palomar, Provincia de Buenos Aires, Argentina, B1685HOE
Argentina, Provincia de Neuquen
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Neuquen, Provincia de Neuquen, Argentina, Q8300PMB
Australia, New South Wales
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Burwood, New South Wales, Australia, 2134
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Darlinghurst, New South Wales, Australia, 2010
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Sydney, New South Wales, Australia, 2010
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Wentworthville, New South Wales, Australia, 2145
Australia, Queensland
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Herston, Queensland, Australia, 4029
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Miami, Queensland, Australia, 4220
Australia, Victoria
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Carlton, Victoria, Australia, 3053
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Melbourne, Victoria, Australia, 3004
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North Fitzroy, Victoria, Australia, 3068
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South Yarra, Victoria, Australia, 3141
Belgium
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Brussels, Belgium, 1000
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Brussels, Belgium, 1200
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Gent, Belgium, 9000
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Leuven, Belgium, B-3000 Leuven
Brazil, RJ
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Rio de Janeiro, RJ, Brazil, 20210-030
Canada, Alberta
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Calgary, Alberta, Canada, T2R0X7
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Edmonton, Alberta, Canada, T6G 2B7
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Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
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Vancouver, British Columbia, Canada, V6B 1R3
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Vancouver, British Columbia, Canada, V6Z 2C7
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Vancouver, British Columbia, Canada, V6Z 2T1
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Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Manitoba
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Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
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Ottawa, Ontario, Canada, K1H 8L6
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Toronto, Ontario, Canada, M5B 1W8
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Toronto, Ontario, Canada, M4N 3M5
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Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
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Montreal, Quebec, Canada, H2L 5B1
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Montreal, Quebec, Canada, H3G 1A4
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Montreal, Quebec, Canada, H2L 4P9
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Montreal, Quebec, Canada, H2X 2P4
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Montreal, Quebec, Canada, H2L 4M1
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Montreal, Quebec, Canada, H2W 1T8
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Sainte-Foy, Quebec, Canada, G1V 4G2
Italy
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Antella (fi), Italy, 50011
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Brescia, Italy, 25123
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Milano, Italy, 20100
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Modena, Italy, 41100
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Roma, Italy
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Roma, Italy, 00185
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Torino, Italy, 10149
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Torino, Italy, 10149
Mexico, Mexico City
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Del. Tlalpan C.p., Mexico City, Mexico, 14050
Mexico, Mexico D.F.
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Del. Tlalpan, C.p., Mexico D.F., Mexico, 14000
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Del. Tlalpan, C.p., Mexico D.F., Mexico, 14080
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Delegacion Tlalpan C. P, Mexico D.F., Mexico, 14080
Netherlands
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Amsterdam, Netherlands, 1091 AC
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Rotterdam, Netherlands, 3015 GD
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Utrecht, Netherlands, 3584 CX
Poland
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Gdansk, Poland, 80-214
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Bydgoszcz, Poland, 85-030
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Chorzow, Poland, 41-500
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Bialystok, Poland, 15-540
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Krakow, Poland, 31-531
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Szczecin, Poland, 71-455
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Warszawa, Poland, 01-201
Puerto Rico
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Rio Piedras, Puerto Rico, 00935
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San Juan, Puerto Rico, 00909
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San Juan, Puerto Rico, 00935
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Stop 15, San Juan, Puerto Rico, 00909
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Ponce, Puerto Rico, 00731
South Africa
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Cape Town, South Africa, 7705
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Cape Town, South Africa, 7405
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Cape Town, South Africa, 7780
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Cape Town, South Africa, 7550
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Johannesburg, South Africa, 2047
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Port Elizabeth, South Africa, 6001
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Pretoria, South Africa, 0132
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Pretoria North, South Africa, 0162
South Africa, Free State
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Bloomfontein, Free State, South Africa, 9301
South Africa, Gauteng
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Johannesburg, Gauteng, South Africa, 2092
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Pretoria, Gauteng, South Africa, 0083
South Africa, Johannesburg
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Soweto, Johannesburg, South Africa, 2013
South Africa, KwaZulu Natal
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Dundee, KwaZulu Natal, South Africa, 3000
Switzerland
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1211 Genève, Switzerland, 14
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Basel, Switzerland, 4031
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Bern, Switzerland, 3010
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Zürich, Switzerland, 8038
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St. Gallen, Switzerland, 9007
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Zürich, Switzerland, 8091
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Lugano, Switzerland, 6900
United Kingdom
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Birmingham, United Kingdom, B9 5SS
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Brighton, United Kingdom, BN2 1ES
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Edinburgh, United Kingdom, EH4 2XU
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London, United Kingdom, SE5 9RS
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London, United Kingdom, SW10 9NH
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London, United Kingdom, NW3 2QG
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London, United Kingdom, W2 1NY
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Manchester, United Kingdom, M8 5RB
United Kingdom, LOTH
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Edinburgh, LOTH, United Kingdom, ED4 2XU
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer Inc ( Director, Clinical Trial Disclosure Group )
Study ID Numbers: A4001026
Study First Received: December 6, 2004
Last Updated: November 12, 2009
ClinicalTrials.gov Identifier: NCT00098293     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Aids
HIV

Additional relevant MeSH terms:
Antimetabolites
Efavirenz
Anti-Infective Agents
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Zidovudine
Lamivudine
Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on November 27, 2009