ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence

• Status: Completed
• Trial end date: 2018-12-07
• Target enrollment: 0
• Participant gender: All

Summary

Purpose: Perform a 3-phase (single dose, multi dose, dose proportionality) study in healthy volunteers using daily tenofovir+emtricitabine, dolutegravir, and maraviroc dosing to quantify intra- and inter-subject variability and dose proportionality. The influence of covariates on ARV hair distribution (e.g., hair growth rate, race, hair color, hair treatment) will also be measured. Using both population PK modeling and physiologic based PK (PBPK) approaches, a statistical model to quantify ARV adherence patterns based on signal intensity/pattern will be developed.

Participants: Healthy volunteers, aged 18 to 70 years of age, inclusive on the date of screening, with an intact gastrointestinal system and at least 1cm caput hair.

Procedures (methods): Participants will be sequentially assigned to enroll in a dosing arm, beginning with maraviroc (MVC), then dolutegravir (DTG), and ending with tenofovir/emtricitabine (TFV/FTC). All participants will take a single observed dose of study product in Phase 1, with blood and hair samples obtained on Days 3, 7, 14, 21 and 28 days post-dose. In Phase 2, all participants take 28 days straight of daily dosing, observed, of the same study product. Blood and hair samples obtained on the same days post-dose. In Phase 3, participants will be randomized to stop their drug, or decrease dosing to one or three doses weekly. Hair and blood samples will again be obtained on the same days post-dose. All participants will complete a follow-up safety visit with 14 days of completing study sampling.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Dolutegravir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Maraviroc; Tenofovir

Criteria

Inclusion Criteria

• Healthy volunteer between the ages of 18 and 70, inclusive on the date of screening, with an intact gastrointestinal tract. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, and clinical laboratory tests

• Recent medical history in good medical standing, without evidence of fever five days prior to enrollment

• HIV-negative

• Able to swallow pills

• Has minimum hair required to provide study samples

• Not allergic to any component of the study drug

• Signed and dated informed consent indicating that they have been informed of all pertinent details of the trial and are willing to participate

• Willing and able to comply with scheduled visits, laboratory tests and trial procedures

• Willing to use at least one form of acceptable birth control throughout the duration of the study

• Negative, or receiving treatment, for syphilis at screening

• Hemoglobin Grade 2 or lower, with no clinically significant medical issues that would preclude blood sampling

Exclusion Criteria

• Age outside of desired range

• Confirmed positive results for HIV, Hepatitis B or C at screening

• Subjects of all genders actively involved in the conception process, in addition to cisgender female subjects who are in the immediate post-partum period or breastfeeding

• Insufficient amount of hair or unwilling to keep hair length at least 1 centimeter throughout duration of study

• Unable or unwilling to comply with all lifestyle measures and/or visits

• Impaired renal function, as documented by a creatinine clearance <80 mL/min with the Cockcroft-Gault equation

• Has donated blood within the past 56 days in the amount greater than 500 mL

• Has taken an investigational drug in the past 4 months

• Clinical, laboratory, or surgical abnormalities that would preclude sample collection

• Has a condition, which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately

• Any clinically significant laboratory result Grade 2 or greater according to the Division of AIDS (DAIDS) Laboratory Grading Tables

• History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week