NCT04302896

Development of a Urine-Based Point-of-Care Test for Adherence to Antiretroviral Drugs

APT-POCT-01: An Open Label, Pharmacokinetic Study of Plasma/Urine/Salivary Drug Concentrations Over Fourteen Days Following Drug Intake Cessation, In HIV-Uninfected Healthy Volunteers Dosing to Steady-state to Further Development of Point of Care Diagnostic Testing

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Rhonda Brand · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This is a single-center, open label study to identify adherence levels of commonly prescribed FDA-approved antiretroviral agents by tracking the decline of drug concentrations in plasma, urine and saliva following abrupt drug cessation in HIV-negative adults. Results from this study may provide support for development of a point of care urine testing device to monitor drug adherence.

Detailed description

Poor adherence to antiretroviral (ARV) therapy and HIV pre-exposure prophylaxis (PrEP) incurs costs for patients, health systems, and society. Non-adherence to ARV precedes viral breakthrough and offers opportunities for health-care professionals to intervene. There is a need for accurate, affordable, rapid, and objective monitoring of adherence to be deployed as a companion diagnostic to ARV therapy. Self-reported questionnaires, physician and nurse adherence consistently over-estimate adherence, and pill counts, and pharmacy returns do not yield sufficient precision for individual patients. Therapeutic drug monitoring (TDM) has the advantage tracking medication intake, but sample storage and processing requirements, turnaround times and relatively high cost preclude their widespread deployment. There is a real clinical need for point-of-care adherence testing, which will have high clinical utility by allowing targeting of adherence support and monitoring, better medication review, and integration with community support. Since the clinical utility of any point-of-care test (POCT) will be its negative predictive value, this trial has been designed as a 'tail' study to track the decline of drug concentrations in plasma, urine and saliva following abrupt drug cessation. Such a study will require dosing to healthy participants who are dosed to steady-state prior to treatment discontinuation. Serial measurement of drug concentrations in plasma, saliva and urine will be used to develop population-based models which adequately describe the kinetics of elimination and population variability in drug exposure. These models will be used to simulate population drug exposures from which target cut-offs are derived for development of a POCT device. Approximately thirty healthy, HIV-uninfected participants will be enrolled and equally assigned to one of two ARV dosing arms using a permuted block design randomization scheme. ARM 1: dolutegravir 50 mg + emtricitabine 200 mg/tenofovir alafenamide 25 mg once daily for 15 days ARM 2: dolutegravir 50 mg + tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg once daily for 15 days To assess ARV pharmacokinetics during dosing and over 14 days following ARV cessation, blood, urine, and saliva samples will be collected at Days 1, 2, 8, 15, 16, 17, 18, 19, 22 and 29.

Conditions

• Medication Adherence
• HIV

Interventions

Type	Name	Description
DRUG	dolutegravir oral tablet 50mg	Tivicay® (dolutegravir, DTG), a HIV-1 integrase strand transfer inhibitor (INSTI), is FDA-approved in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and in pediatric patients weighing at least 30kg. Tivicay® 50mg tablets \[GlaxoSmithKline\] are yellow, round, film-coated, biconvex tablets debossed with "SV 572" on one side and "50" on the other side. The inactive ingredients in each tablet are D-mannitol, microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl fumarate. The tablet film-coating contains the inactive ingredients iron oxide yellow macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc, and titanium dioxide.
DRUG	emtricitabine/tenofovir alafenamide oral tablet 200mg/25mg	Descovy® (emtricitabine/tenofovir alafenamide, FTC/TAF) is a combination of two HIV nucleoside analog reverse transcriptase inhibitors (NRTIs) FDA-approved in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35kg. Descovy® 200 mg/25 mg tablets \[Gilead\] are blue, rectangular-shaped, and film-coated with "GSI" debossed on one side and "225" on the other side. The inactive ingredients are croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The tablets are film-coated with a coating material containing indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
DRUG	tenofovir disoproxil fumarate oral tablet 300mg	Viread® (tenofovir DF, TDF) is a nucleotide analog HIV-1 reverse transcriptase inhibitor and a hepatitis B reverse transcriptase inhibitor FDA-approved for the treatment of HIV-1 infection in combination with other antiretroviral agents and for the treatment of chronic hepatitis B in adults and pediatric patients 2 years of age and older weighing at least 10kg. Viread® 300mg tablets \[Gilead\] are almond-shaped, light blue, film-coated tablets containing 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil, are debossed with "GILEAD" and "4331" on one side and with "300" on the other side. The inactive ingredients in each tablet are croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. Viread® 300mg tablets are coated with Opadry II Y-30-10671-A, which contains FD\&C blue #2 aluminum lake, hypromellose 2910, lactose monohydrate, titanium dioxide, and triacetin.
DRUG	lamivudine oral tablet 300mg	Lamivudine (Epivir®, 3TC) is a nucleoside analogue reverse transcriptase inhibitor FDA-approved in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients at least 3 months of age. Lamivudine 300mg tablets \[Apotex Inc.\] are gray, modified diamond-shaped, film-coated, and engraved with "LMV 300" on one side and APO on the reverse side. Inactive ingredients are black iron oxide, colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose anhydrous, magnesium stearate, polyethylene glycol, and titanium dioxide.

Timeline

• Start date: 2020-08-31
• Primary completion: 2021-09-30
• Completion: 2021-09-30
• First posted: 2020-03-10
• Last updated: 2022-03-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study