A Phase 1B Study of the Safety and Pharmacokinetics of Ritonavir-Boosted Elvitegravir (GS-9137/r) Plus a Background Regimen (BR) in HIV-1 Infected, Antiretroviral Treatment-Experienced Adolescents
- Conditions
- Human Innunodeficiency Virus (HIV-1) InfectionsMedDRA version: 9.1Level: LLTClassification code 10020192Term: HIV-1
- Registration Number
- EUCTR2008-003917-29-GB
- Lead Sponsor
- Gilead Sciences Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
• 12 years to < 18 years of age (consent of parent or guardian required per local state or country law)
• Subjects able to give written assent prior to any screening evaluations and willing to comply with study requirements
• Parent or guardian able to give written informed consent prior to any screening
evaluations and willing to comply with study requirements
• Body Surface Area (BSA) = 1.2 m2
• Weight = 40 kg (88 lbs)
• Able to swallow oral tablets
• HIV-1 RNA >1,000 copies/mL OR < 400 copies/mL at screening
• Six months of antiretroviral treatment experience or at least one documented resistance mutation as defined by current IAS-USA Guidelines.These resistant gene mutations must be documented in a historical genotype report(s), or in the genotype/phenotype report at screening provided by Gilead Sciences.
• Subjects must have been on a stable antiretroviral regimen (or be off antiretroviral
therapy completely) for at least 30 days prior to the Screening visit. Subjects undergoing dose modifications to their antiretroviral regimen for growth, or switching medication formulations are considered to be on a stable antiretroviral regimen.
•Subjects must be able to receive at least two fully-active antiretroviral agents one of which one must be a fully-active ritonavir-boosted protease inhibitor (PI/r) (fully-active is defined by phenotypic analysis as being below the lower clinical or biological cutoff for each drug). (NOTE: This inclusion criteria is not applicable for subjects with
screening HIV-1 RNA < 400 copies/mL)
• Normal ECG (or if abnormal, determined by investigator to be not clinically significant)
• Adequate renal function:
Estimated glomerular filtration rate = 60 mL/min/1.73m2
Estimated Glomerular Filtration Rate (GFR) using Schwartz Formula
(mL/min/1.73m2) = k × L/Scr
[(k is a proportionality constant: for adolescent females = 12 years old is 0.55; and for adolescent males = 12 years old is 0.70); L is height in centimeters (cm); and Scr is serum creatinine (mg/dL)]
• Hepatic transaminases (AST and ALT) = 2.5 × 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
= 25,000/mm3; hemoglobin = 8.0 g/dL)
• Prothrombin time = 1.25 × ULN
• Serum lipase = 1.5 × ULN
• Negative serum pregnancy test (females)
• Females (of childbearing potential i.e., not surgically sterile) must agree to utilize
effective contraception methods [two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual
abstinence or have a vasectomized partner (confirmed sterile)] while on 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
• 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
• Life expectancy = 1 year
Are
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
• A new AIDS-defining condition diagnosed within the 30 days prior to screening (Refer to Appendix 6 of the protocol).
• Prior treatment with any HIV-1 integrase inhibitor
• Females who are breastfeeding
• Subjects receiving ongoing therapy with any medication that is not to be taken with a component of the BR, including drugs not to be taken with ritonavir (refer to prescribing information)
Administration of any of the medications mentioned in the protocol must be discontinued at least 30 days prior to the Baseline visit/Day 1 and for the duration of the study.
• Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance
• Active malignancy or treatment for active malignancy other than cutaneous Kaposi’s
sarcoma (KS) or basal cell carcinoma in the last two years. Subjects with biopsyconfirmed 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 (other than oral) antibiotic or anti-fungal therapy within 30 days prior to baseline, unless agreed upon by the GSI Medical Monitor
• Participation in any other clinical treatment trial 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the steady-state pharmacokinetics (PK) and confirm the dose of ritonavirboosted elvitegravir (GS-9137/r) in HIV-1 infected antiretroviral treatment-experienced adolescent subjects.;Secondary Objective: To evaluate the safety and tolerability of ritonavir-boosted elvitegravir (GS-9137/r) in<br>HIV-1 infected antiretroviral treatment-experienced adolescents.;Primary end point(s): To evaluate the steady-state pharmacokinetics (PK) and confirm the dose of ritonavirboosted elvitegravir (GS-9137/r) in HIV-1 infected antiretroviral treatment-experienced adolescent subjects.
- Secondary Outcome Measures
Name Time Method