Study to assess the pharmacokinetics of plasma doravirine once daily over 72 hours following drug intake cessation at steady-state in healthy volunteers
The administration of combination antiretroviral therapy (cART) to HIV-infected patients has been associated with a dramatic reduction in AIDS-related morbidity and mortality. The key to successful HIV drug treatment is adhering to the prescribed combination every day. The approval of single tablet combinations (STRs) provides HIV care providers with a "one tablet once a day" therapy, making adherence much easier for patients. However, in HIV therapy, successful adherence also means attention to intervals between doses or dietary restrictions. Ideally, to guarantee long-term virological response, HIV-infected patients should take their cART every day at the same time. However, cART is for life and doses can be forgotten or delayed. For this study 14 healthy volunteers will receive Pifeltro® (doravirine 100mg tablets) daily for 7 days to reach steady state. Following the last dose samples will be taken for pharmacokinetic testing over 72 hours. The incidence of adverse events between enrolment to the study (day 1) and last visit (day 20-23) will be recorded. Blood, urine and faecal samples from study subjects will be taken for use in planned exploratory research and for use in future research: Analyses looking at genes which affect drug disposition (pharmacogenomics); the impact of doravirine intake on platelet function and markers of platelet and endothelial cell activation; metabolic changes associated with doravirine.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
24
Non-nucleoside reverse transcriptase inhibitor. Administered as film coated tablet.
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom
Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose.
Following cessation of daily doravirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours. Blood samples were collected pre-dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 h post-dose
Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment
Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72h Post-dose
Following cessation of daily dorovirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours. Blood samples were collected at pre-dose and at 2,4,8,12,24,30,36,47,60 and 72h post-dose
Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment
Steady State Plasm Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose
Following cessation of daily dorovirine, plasma concentrations of drug to be taken before last dose and at 11 further timepoints over 72 hours. Blood samples were collected pre-dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72h post-dose
Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment
Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose.
Following cessation of daily dorivirine, plasm concentrations of drug to be taken were collected pre-dose and at 2,4,8, 12, 24, 30, 36, 48, 60 and 72h post-dose
Time frame: 72 hours from treatment cessation; days 7-10 inclusive from enrolment
Number of Participants With Treatment-emergent Adverse Events
All adverse events to be recorded and reported during the study up to last visit.
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Time frame: From enrolment to last visit; last visit will be between days 20-23 from enrolment