A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) Each Administered With a Background Regimen in HIV-1 Infected, Antiretroviral Treatment-Experienced Adults.
- Conditions
- AIDS10047438
- Registration Number
- NL-OMON33886
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
Subjects participating in Study GS-US-183-0144 who have either met all screening criteria or have enrolled are eligible to participate and continue with their regular visit schedule. Subjects must consent to participate in Study GS-US-183-0145.;* Plasma HIV-1 RNA levels * 1,000 copies/mL at screening using the AmpliPrep/Taqman HIV-1 Test®
* Subjects must have documented resistance, as defined by current IAS-USA definitions, or at least six months experience prior to screening with two or more different classes of antiretroviral agents.
* Subjects must be eligible to receive one of the fully-active ritonavir-boosted-PIs, based on the results of screening phenotype analysis provided by Monogram Biosciences, and an allowed second agent. Fully-active PIs are defined as those with fold changes below the lower clinical or biological cutoff for each drug.
* Normal ECG (or if abnormal, determined by the investigator to be not clinically
significant).
*Adequate renal function: Estimated glomerular filtration rate * 60 mL/min according to the Cockcroft-Gault formula
* Hepatic transaminases (AST and ALT) * 5 × upper limit of normal (ULN).
* Total bilirubin * 1.5 mg/dL, or normal direct bilirubin (subjects with documented
Gilbert*s Syndrome or hyperbilirubinemia due to indinavir or atazanavir therapy may
have total bilirubin up to 5 × ULN).
* Adequate hematologic function (absolute neutrophil count * 1,000/mm3; platelets
* 50,000/mm3; hemoglobin * 8.5 g/dL).
* Serum amylase < 1.5 × ULN (subjects with serum amylase * 1.5 × ULN will remain
eligible if serum lipase is * 1.5 × ULN).
* Negative serum pregnancy test (females of childbearing potential only).
* Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs.
* Female subjects who utilize hormonal contraceptive as one of their birth control
methods must have used the same method for at least three months prior to study
dosing.
* Female subjects who are postmenopausal for less than two years are required to have
FSH > 40 mIU/mL. If the FSH is * 40 mIU/mL, the subject must agree to use highly
effective method of birth control (as described above) to participate in the study.
* Male subjects who are sexually active must be willing to use effective barrier
contraception (e.g., condom with spermicide) during heterosexual intercourse from
screening through completion of the study and continue for at least 30 days from date of last dose of study drug.
* Age * 18 years.
* Life expectancy * 1 year.
* The ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures.
* A new AIDS-defining condition diagnosed within the 30 days prior to screening
* Prior treatment with any HIV-1 integrase inhibitor
* Subjects experiencing ascites
* Subjects experiencing encephalopathy
* Females who are breastfeeding
* Positive serum pregnancy test at any time during the study (female of childbearing
potential)
* Subjects receiving ongoing therapy with any medication listed below that is not to be taken with a component of the BR, including drugs not to be used with ritonavir (refer to prescribing information)
* Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance.
* A history of or ongoing mailgnancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and are not anticipated to require systemic therapy during the study.
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.
* Participation in any other clinical trial (except for the Etravirine or Maraviroc expanded access
programs), without prior approval from the sponsor, is prohibited while participating in this trial.
* Any other clinical condition or prior therapy that, in the opinion of the investigator,
would make the subject unsuitable for the study or unable to comply with the dosing requirements.
* Known hypersensitivity to the study drugs, the metabolites or formulation excipients.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the proportion of subjects<br /><br>achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL<br /><br>through Week 48.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* The proportion of subjects achieving and maintaining<br /><br>confirmed HIV-1 RNA < 400 copies/mL through Week 48<br /><br>* The proportion of subjects with HIV-1 RNA < 50 copies/mL at<br /><br>Week 48<br /><br>* The time to pure virologic failure for HIV-1 RNA cutoff at 50 copies/mL up to<br /><br>Week 48<br /><br>* The time to pure virologic failure for HIV-1 RNA cutoff at 400 copies/mL up<br /><br>to Week 48<br /><br>* The proportion of subjects with HIV-1 RNA < 400 copies/mL<br /><br>at Week 48<br /><br>* The change from baseline in log10 HIV-1 RNA (copies/mL) at<br /><br>Week 48<br /><br>* The change from baseline in CD4+ cell count at Week 48</p><br>