Assessment of a New "Boosting" Strategy for HIV Pre-exposure Prophylaxis in Healthy Volunteers

NCT ID: NCT03202511

Last Updated: 2021-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-23
• Study Completion Date: 2018-07-02

Brief Summary

The study will be a randomized, open-label, cross-over clinical pharmacokinetic trial to investigate a strategy for probenecid "boosting" in the setting of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP). The study will be conducted at the Indiana University Clinical Research Center. All samples will be processed and the amount of tenofovir/FTC in plasma, blood, and urine, and tenofovir diphosphate and emtricitabine in peripheral blood mononuclear cells will be determined using validated analytical methods developed by the investigators at the University of Colorado. Probenecid plasma and urine concentrations will also be measured using an in-house assay. Following completion of the study, the secondary aim will be accomplished via analysis of selected samples collected at baseline and following treatment. Those selected samples will be assessed for urinary markers of proximal tubulopathy (urine total protein, albumin, creatinine, phosphorus, retinol binding protein, and beta-2-microglobulin) and serum alkaline phosphatase, osteocalcin, procollagen type 1 N propeptide, cystatin C, and creatinine to determine if the probenecid boosting strategy does indeed lead to less potential renal and bone toxicity.

Conditions

Pre-Exposure Prophylaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Control

The control phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on day 1 (2 tablets) followed by 300/200 mg (1 tablet) doses on days 2 and 3.

Group Type: ACTIVE_COMPARATOR

Tenofovir disoproxil fumarate/Emtricitabine

Intervention Type: DRUG

Included in arm/group descriptions.

Treatment

The treatment phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (2 tablets) along with a 2 gram oral probenecid (PRO) dose (4 tablets, 500 mg each) on day 1.

Group Type: EXPERIMENTAL

Probenecid Oral Tablet

Intervention Type: DRUG

Included in arm/group descriptions.

Tenofovir disoproxil fumarate/Emtricitabine

Intervention Type: DRUG

Included in arm/group descriptions.

Interventions

Probenecid Oral Tablet

Included in arm/group descriptions.

Intervention Type: DRUG

Tenofovir disoproxil fumarate/Emtricitabine

Included in arm/group descriptions.

Intervention Type: DRUG

Other Intervention Names

TDF/FTC, Truvada

Eligibility Criteria

Inclusion Criteria

1. 18 to 55 years old healthy (as decided from a pre-enrollment screening session described above) male participants within 32% of their ideal body weight.

2. Individuals who agree to refrain from taking any prescriptions medications, over-the-counter medications (including salicylates/aspirin), hormonal agents, and herbal, dietary, and alternative supplements that may interact with the metabolism of those study drugs at least 2 weeks prior to the start of the study and until study completion.

3. Nonsmoker or individuals willing to refrain from smoking or use of tobacco or marijuana for at least one month prior to and until the completion of the study (the entire study lasts for approximately 49 days).

Exclusion Criteria

• 1. Are underweight (weigh less than 52 kg or 114 lb) or overweight [body mass index (BMI) greater than 32].

2. Females will be excluded to reduce study variability for this first proof of concept study.

3. Have insufficient renal function (estimated Creatinine Clearance ≤ 90 mL/min).

4. Have history of current alcohol or drug abuse (more than 4 alcoholic drinks per day on a regular basis).

5. Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tenofovir disoproxil fumarate/ emtricitabine, probenecid).

6. Have taken TDF or FTC as part of pre-exposure prophylaxis within the past 6 weeks.

7. Any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, gout, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, chronic active hepatitis B virus (HBV) infection, or HIV.

8. History of anemia or any other significant hematologic disorder. 9. Have history or current gastrointestinal disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs.

10. Have a serious infection within the last week before study enrollment. 11. Have donated blood within the past two months. 12. Have blood results that do not fall in a healthy range (e.g., blood hemoglobin less than 12.0 mg/dl).

13. Are taking on regular basis substances that may interfere with the metabolism (breakdown) of study medications by the body, including prescription medications, over-the-counter, herbal or dietary supplements, alternative medications, or hormonal agents (i.e. oral contraceptives, intra-uterine device with hormones).

14. Have a life style that places subjects at a higher risk for contracting HIV during the study period (e.g. active illicit drug use, excessive alcohol drinking, sexually transmitted infection (including gonorrhea, chlamydia, syphilis, herpes, human papilloma virus) within the past one year, or having more than one sexual partner in the past 6 months).

15. Positive HIV antibody test. 16. Positive HBV surface antigen test. 17. Have participation in a research study or use of an investigational drug in the last one month.

18. Are employed or are student under supervision of any of the investigators of this study.

19. Cannot state a good understanding of this study including risks and requirements; are unable to follow the rules of this study.

20. Cannot commit the time requested for this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Zeruesenay Desta

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brandon T Gufford, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana Unversity School of Medicine

Locations

Indiana University Clinical Research Center at University Hospital

Indianapolis, Indiana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1705315090

Identifier Type: -

Identifier Source: org_study_id