| |
New CCR5 Inhibitor UK-427,857 Study for Treatment-Naives
|
| |
| |
Trial of UK-427,857 in Combination with Zidovudine/Lamivudine versus Efavirenz in Combination with Zidovudine/Lamivudine for the Treatment of HIV-1 Infected Subjects
Phase II/III
FOR LOCATION & CONTACT INFORMATION:
Call: 734-622-7600
ClinicalTrials.gov@Pfizer.com
North Carolina: Pfizer Investigational Site, Huntersville, North Carolina, 28078, United States; Recruiting
This study is currently recruiting patients.
Sponsored by: Pfizer
Information provided by: Pfizer
Study Design: Treatment, Randomized, Double-Blind, Active Control, 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-naïve HIV-1 Infected Subjects
Expected Total Enrollment: 1071
Study start: December 2004
Purpose
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.
Eligibility
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
|
|
| |
| |
|
|
|
