The purpose of this study is to describe drug concentrations in blood plasma, rectal fluid, rectal tissue, and seminal fluid in HIV negative men following single and multiple doses of an investigational HIV medication known as GSK1349572 (dolutegravir).
The purpose of this study is to determine first dose and steady-state concentrations of GSK1349572 in seminal fluid, rectal mucosal fluid, and rectal tissue compared to blood plasma (BP) in HIV-1 negative males. GSK1349572 is an investigational next generation integrase inhibitor currently in Phase III trials. Understanding the concentrations of GSK1349572 in multiple male biological compartments will inform its role in preventing HIV infection by making an HIV-infected person less likely to transmit the virus, and protecting uninfected persons from acquiring the virus.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Subjects will take a GSK1349572 (dolutegravir) 50mg tablet by mouth once daily for 8 days. GSK1349572 concentrations will be measured in blood plasma, seminal fluid, rectal fluid, and rectal tissue over 24 hours after a single dose and over two 24 hour periods once steady state is reached. Blood plasma will be collected pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours after dosing. Each subject will also provide a total of 9 seminal and rectal fluid samples and have 2 rectal tissue biopsies performed pre-dose or at 1, 3, 6, 12, 18, or 24 hours after receiving single or multiple doses.
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States
Area under the concentration versus time curve (AUC) in blood plasma after a single dose
The area under the concentration time curve will be determined from all sample collection time points over a 24 hour period. Sample collection for blood plasma will occur pre-dose, then 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose. AUCs will be determined for individual subjects and for all subjects combined following a single dose.
Time frame: 24 hours
Peak concentration (Cmax) in blood plasma after a single dose
Peak drug concentration in blood plasma after the first dose will be determined from samples taken pre-dose, then at 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose in each subject and across all subjects.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) in blood plasma at steady state
The area under the concentration time curve will be determined from all sample collection time points over a 24 hour period. Sample collection for blood plasma will occur pre-dose, then 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose. AUCs will be determined for individual subjects and for all subjects combined at steady state.
Time frame: 24 hours
Peak concentration (Cmax) in blood plasma at steady state
Peak drug concentration in blood plasma at steady state will be determined from samples taken pre-dose, then at 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 hours post-dose in each subject and across all subjects.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) in seminal fluid after a single dose
The area under the concentration time curve after a single dose will be determined from all sample collection time points over a 24 hour period for seminal fluid. Sample collection will occur pre-dose and at two time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. AUCs will be determined for all subjects combined.
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Time frame: 24 hours
Peak drug concentration (Cmax) in seminal fluid after a single dose
Peak drug concentration in seminal fluid will be determined from samples taken pre-dose, then at 2 time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. Cmax will be determined for all subjects combined.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) for seminal fluid at steady state
The area under the concentration time curve at steady state for seminal fluid will be determined from all sample collection time points over a 48 hour period for seminal fluid. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. AUCs will be determined for each subject and across all subjects.
Time frame: 48 hours
Peak drug concentration (Cmax) for seminal fluid at steady state
Peak drug concentration (Cmax) at steady state for seminal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. Cmax will be determined for each subject and across all subjects.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) for rectal fluid after a single dose
The area under the concentration time curve after a single dose will be determined from all sample collection time points over a 24 hour period for rectal fluid. Sample collection will occur pre-dose and at two time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. AUCs will be determined for all subjects combined.
Time frame: 24 hours
Peak drug concentration (Cmax) in rectal fluid after a single dose
Peak drug concentration in rectal fluid will be determined from samples taken pre-dose, then at 2 time points per subject 1, 3, 6, 12, 18, or 24 hours post-dose. Cmax will be determined for all subjects combined.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) for rectal fluid at steady state
The area under the concentration time curve at steady state for rectal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. AUCs will be determined for each subject and across all subjects.
Time frame: 48 hours
Peak drug concentration (Cmax) for rectal fluid at steady state
Peak drug concentration (Cmax) at steady state for rectal fluid will be determined from all sample collection time points over a 48 hour period. Sample collection will occur at 1, 3, 6, 12, 18, or 24 hours post-dose over 48 hours with 3 collections per subject in each 24 hour period. Cmax will be determined for each subject and across all subjects.
Time frame: 48 hours
Area under the concentration versus time curve (AUC) for rectal tissue after a single dose
The area under the concentration time curve for rectal tissue after a single dose will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and AUC will be determined for all subjects combined.
Time frame: 24 hours
Peak drug concentration (Cmax) for rectal tissue after a single dose
Peak drug concentration in rectal tissue after a single dose will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and Cmax will be determined for all subjects combined.
Time frame: 24 hours
Area under the concentration versus time curve (AUC) for rectal tissue at steady state
The area under the concentration time curve for rectal tissue at steady state will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and AUC will be determined for all subjects combined.
Time frame: 24 hours
Peak drug concentration (Cmax) for rectal tissue at steady state
Peak drug concentration in rectal tissue at steady state will be determined from all sample collection time points over a 24 hour period. One sample collection will be performed per subject at either 1, 3, 6, 12, 18, or 24 hours post-dose and Cmax will be determined for all subjects combined.
Time frame: 24 hours
Area under the concentration versus time curve ratios after a single dose
AUC ratios will be determined to compare blood plasma concentrations after a single dose with concentrations in rectal tissue, rectal fluid, and seminal fluid.
Time frame: 24 hours
Area under the concentration time curve ratios at steady state
AUC ratios will be determined to compare blood plasma concentrations at steady state with concentrations in rectal tissue, rectal fluid, and seminal fluid.
Time frame: 24 hours
Accumulation ratio
Area under the concentration time curve (AUC) in each matrix at steady state will be compared to AUC after a single dose to determine accumulation ratios.
Time frame: 24