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, 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 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: UK-427,857 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), 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 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	Treatment or Intervention	Phase
HIV Infection	Drug: UK-427,857	Phase II Phase III

Further Study Details: 

Expected Total Enrollment:  1071

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  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°C 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 judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Call:      734-622-7600    ClinicalTrials.gov@Pfizer.com

Alabama
      Pfizer Investigational Site, Birmingham,  Alabama,  35294,  United States; Recruiting
California
      Pfizer Investigational Site, Los Angeles,  California,  90046,  United States; Recruiting
      Pfizer Investigational Site, San Francisco,  California,  94115,  United States; Recruiting
Florida
      Pfizer Investigational Site, Altamonte Springs,  Florida,  32701,  United States; Recruiting
      Pfizer Investigational Site, Miami,  Florida,  33133,  United States; Recruiting
North Carolina
      Pfizer Investigational Site, Huntersville,  North Carolina,  28078,  United States; Recruiting
South Carolina
      Pfizer Investigational Site, Columbia,  South Carolina,  29206,  United States; Recruiting
Texas
      Pfizer Investigational Site, Dallas,  Texas,  75246,  United States; Recruiting
Australia
      Pfizer Investigational Site, Darlinghurst,  2010,  Australia; Recruiting
Australia, New South Wales
      Pfizer Investigational Site, Darlinghurst,  New South Wales,  2010,  Australia; Recruiting
      Pfizer Investigational Site, Darlinghurst,  New South Wales,  2010,  Australia; Recruiting
Australia, Queensland
      Pfizer Investigational Site, HERSTON,  Queensland,  4029,  Australia; Recruiting
      Pfizer Investigational Site, Miami,  Queensland,  4220,  Australia; Recruiting
United Kingdom
      Pfizer Investigational Site, London,  SW10 9TH,  United Kingdom; Recruiting

Study ID Numbers:  A4001026
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  December 6, 2004
ClinicalTrials.gov Identifier:  NCT00098293
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08