None listed
Conditions
Brief summary
This Phase 1 study will evaluate the safety, tolerability, and PK of oral GS 3107 in combination with oral ECD in healthy participants. The results from this study will inform the feasibility of long interval dosing of GS 3107 with ECD for the prevention of HIV 1 infection, or to be used in combination with other antiretroviral agents for HIV 1 treatment. This study provides comparisons of PK and generates safety data for the expected therapeutic range of drug exposures planned for evaluation in subsequent studies. This is an open label study with adaptive dose selection in healthy adult participants to evaluate the effect of coadministration of GS 3107 and ECD on the PK of LEN (administered as LEN prodrug, GS-3107) in Part A (Cohorts 1 through 4) Cohorts 3 to 8 are optional cohorts which will only initiate if deemed necessary at the discretion of the sponsor based on Safety Review Team review of safety, tolerability, and available PK data from all participants enrolled in the previous dosing cohort(s). The additional cohorts will evaluate the effect of food on the PK of ECD in Part B, and the effect of P-gp inhibition by ECD on a probe substrate in Part C, and the PK of GS-3107 when given alone in Part D.
Interventions
The study will proceed governed by a review of safety and available PK data and applicable stopping rules. Each cohort listed below is open label. All participants enrolled per cohort will be allocated to the same condition and dose, there are no arms within each cohort. Dose selection, dose frequency, duration of split between doses, dose and meal conditions (including fat/calorie content) will be determined by Safety Review Team evaluation of previous dosing cohorts. If fasting, no food or dri
The study will proceed governed by a review of safety and available PK data and applicable stopping rules. Each cohort listed below is open label. All participants enrolled per cohort will be allocated to the same condition and dose, there are no arms within each cohort. Dose selection, dose frequency, duration of split between doses, dose and meal conditions (including fat/calorie content) will be determined by Safety Review Team evaluation of previous dosing cohorts. If fasting, no food or drink, except water, for at least 10 hours. The dose for Cohort 3 will be determined following Safety Review Team evaluation of previous dosing cohorts included in listing ACTRN12625001353482. The dose for Cohort 4 will be determined based Safety Review Team evaluation of previous cohorts. Part A: Cohorts 3 and 4 (GS-3107 + encequidar methanesulfonate (ECD)) Cohort 3: up to 5600 mg GS-3107 oral tablets coadministered with up to 360 mg ECD oral tablets, in fasted or fed state (low- or moderate-fat meal), as a single dose or a split dose: Single dose: 1 dose of up to 2800 mg GS-3107 coadministered with up to 180 mg ECD on Day 1. Split dose: 2 doses of up to 2800 mg GS-3107 coadministered with 2 doses of up to 180 mg ECD (up to 5600 mg GS-3107 and up to 360 mg ECD total). Doses will be given 12 hours apart (in the morning and evening on Day 1) or 24 hours apart (in the morning of Day 1 and the morning of Day 2). Total daily dose of GS-3107 will not exceed 2800 mg and total daily dose of ECD will not exceed 180 mg. Cohort 4: up to 5600 mg GS-3107 oral tablets coadministered with up to 360 mg ECD oral tablets, in fasted or fed state (low- or moderate-fat meal), as a single dose or a split dose:: Single dose: 1 dose of up to 2800 mg GS-3107 coadministered with up to 180 mg ECD on Day 1. Split dose: 2 doses of up to 2800 mg GS-3107 coadministered with 2 doses of up to 180 mg ECD (up to 5600 mg GS-3107 and up to 360 mg ECD total). Doses will be given 12 hours apart (in the morning and evening on Day 1) or 24 hours apart (in the morning of Day 1 and the morning of Day 2). Total daily dose of GS-3107 will not exceed 2800 mg and total daily dose of ECD will not exceed 180 mg. Monitoring of aderence will be conducted by site.
Sponsors
Gilead Sciences Inc
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must meet the following key inclusion criteria: - Healthy males and females aged between 18 and 55 - BMI between 19 and 32 kg/m 2 - Be a non-smoker with the discontinuation of nicotine or nicotine containing products greater than or equal to 90 days prior to first dose of the study drug - Not currently take any regular prescription medication - If a female of childbearing potential and engage in heterosexual intercourse, must be on a non-hormonal form of contraception or have a partner that has had a vasectomy and refrain from egg donation and in vitro fertilization during the study through the end of the contraception requirement - If male of childbearing potential and engage in heterosexual intercourse, must agree to use condoms and refrain from sperm donation during the study through the end of the contraception requirement - Be at low risk of HIV-1 as assessed by the investigator - Have a negative pregnancy test at screening and admission
Exclusion criteria
Participants who meet any of the following key exclusion criteria are not eligible to be enrolled in this study: - Have known hypersensitivity to the study drug or its components - Have a serious or active medical or psychiatric illness that would interfere with participant treatment, assessment or compliance with the protocol in the opinion of the investigator - Are currently breastfeeding - Have current alcohol or substance abuse judged by the investigator to interfere with compliance or safety, or a positive drug or alcohol test at screening or admission - Have a positive test result for HIV-1/2, hepatitis B, or hepatitis C at screening - Require ongoing prohibited medications or have recently used study drugs or immunosuppressive therapies - Have taken any prescription medications or over-the-counter medications within 28 days prior to the start of study drug dosing - Plan to donate sperm or eggs during or within 60 days after the study
Outcome results
None listed