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

NCT04302896 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: STUDY19100009R01AI122301
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Medication Adherence; HIV

Keywords

Antiretroviral; Pharmacokinetics; Urine Test; HIV negative

Outcome Measures

Primary Outcomes (5)

• Maximum concentration (Cmax) of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites

  Cmax of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites in plasma, whole blood (dried spot), saliva, and urine as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)

  Pre-dose; 24, 168, and 336 after the first dose; then 24, 48, 72, 98, 168, and 336 hours after the final dose

• Time to maximum concentration (Tmax) of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites

  Tmax of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites in plasma, whole blood (dried spot), saliva, and urine as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)

  Pre-dose; 24, 168, and 336 after the first dose; then 24, 48, 72, 98, 168, and 336 hours after the final dose

• Minimum concentration (Cmin) of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites

  Cmin of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites in plasma, whole blood (dried spot), saliva, and urine as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)

  Pre-dose; 24, 168, and 336 after the first dose; then 24, 48, 72, 98, 168, and 336 hours after the final dose

• Area under the concentration-time curve (AUC) of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites

  AUC of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, tenofovir alafenamide, and metabolites in plasma, whole blood (dried spot), saliva, and urine as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)

  Pre-dose; 24, 168, and 336 after the first dose; then 24, 48, 72, 98, 168, and 336 hours after the final dose

• Half-life (t½) of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, and tenofovir alafenamide

  Estimated t½ of dolutegravir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, and tenofovir alafenamide as measured in plasma, whole blood (dried spot), saliva, and urine

  Pre-dose; 24, 168, and 336 after the first dose; then 24, 48, 72, 98, 168, and 336 hours after the final dose

Study Arms (2)

dolutegravir + emtricitabine/tenofovir alafenamide

EXPERIMENTAL

Tivicay® (dolutegravir 50 mg tablet) + Descovy® (emtricitabine 200 mg/tenofovir alafenamide 25 mg combination tablet), one tablet of each taken by mouth once daily for 15 days

Drug: dolutegravir oral tablet 50mg; Drug: emtricitabine/tenofovir alafenamide oral tablet 200mg/25mg

dolutegravir + tenofovir disoproxil fumarate + lamivudine

EXPERIMENTAL

Tivicay® (dolutegravir 50 mg tablet) + Viread® (tenofovir disoproxil fumarate 300 mg tablet) + lamivudine 300 mg tablet, one tablet of each taken by mouth once daily for 15 days

Drug: dolutegravir oral tablet 50mg; Drug: tenofovir disoproxil fumarate oral tablet 300mg; Drug: lamivudine oral tablet 300mg

Interventions

dolutegravir oral tablet 50mg DRUG

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.

Also known as: Tivicay®, DTG

dolutegravir + emtricitabine/tenofovir alafenamide; dolutegravir + tenofovir disoproxil fumarate + lamivudine

emtricitabine/tenofovir alafenamide oral tablet 200mg/25mg DRUG

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.

Also known as: Descovy®, FTC/TAF

dolutegravir + emtricitabine/tenofovir alafenamide

tenofovir disoproxil fumarate oral tablet 300mg DRUG

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.

Also known as: Viread®, tenofovir DF, TDF

dolutegravir + tenofovir disoproxil fumarate + lamivudine

lamivudine oral tablet 300mg DRUG

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.

Also known as: Epivir®, 3TC

dolutegravir + tenofovir disoproxil fumarate + lamivudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at screening, verified per site standard operating procedure (SOP)
• Not pregnant or breastfeeding
• Availability to return for all study visits, barring unforeseen circumstances
• Willing and able to
• communicate in English
• provide written informed consent to take part in the study
• provide adequate locator information, as defined in site SOP
• follow the assigned dosing protocol and maintain an accurate dosing log
• Must agree not to participate in other concurrent interventional and/or drug trials
• Understands and agrees to local sexually transmitted infections (STI) reporting requirements
• HIV-1 seronegative at screening
• Must be in general good health in the opinion of the investigator
• For female participants of reproductive potential: Using an effective method of contraception and intending to continue use of an effective method for the duration of study participation and for 8 weeks after the last dose of study drug. Acceptable methods include:
• hormonal methods
• IUD (intrauterine device)

You may not qualify if:

• Participant reports any of the following at Screening:
• Has plans to relocate away from the study site area during the period of study participation
• Pregnant, less than 3 months post-partum, or lactating
• Intends to become pregnant during the period of study participation
• History of adverse reaction to study drugs
• History of osteoporosis or osteopenia
• PrEP (pre-exposure prophylaxis) or (PEP) post-exposure prophylaxis for HIV exposure within 3 months - prior to screening
• Participating in another research study involving drugs or medical devices within 3 months or 5 half-lives (if known) prior to enrollment
• History of gastric bypass
• History of inflammatory bowel disease
• Currently taking or anticipation of taking any medications on list of prohibited medications as specified in section 4.10.
• Unwilling or unable to comply with study procedures, medications and visits
• Allergies to dyes, excipients and components of drugs
• Condomless insertive or receptive anal intercourse with more than one partner in the past six months
• Known HIV-positive sexual partner within the last 6 months

Sponsors & Collaborators

• Rhonda Brand: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

HIV/AIDS Clinical Research Unit / University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Else LJ, Dickinson L, Edick S, Zyhowski A, Ho K, Meyn L, Dilly-Penchala S, Thompson B, Shaw V, Khoo S, Brand RM. Tenofovir, emtricitabine, lamivudine and dolutegravir concentrations in plasma and urine following drug intake cessation in a randomized controlled directly observed pharmacokinetic trial to aid point-of-care testing. J Antimicrob Chemother. 2024 Jul 1;79(7):1597-1605. doi: 10.1093/jac/dkae147.

  PMID: 38758205 DERIVED

MeSH Terms

Conditions

Medication Adherence

Interventions

dolutegravir; Emtricitabine; tenofovir alafenamide; emtricitabine tenofovir alafenamide; Tenofovir; Lamivudine

Condition Hierarchy (Ancestors)

Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Zalcitabine; Dideoxynucleosides

Study Officials

• Rhonda Brand, PhD

  University of Pittsburgh

  STUDY CHAIR

• Ken Ho, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: randomized, open-label

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: August 31, 2020
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)