Body Compartment Pharmacokinetics of Anti- Retroviral Agents That May be Used for Future HIV Post- Exposure Prophylaxis.

NCT03472963 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00101179
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to determine if the uptake of anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues.

Conditions

HIV Infections

Keywords

Post-Exposure Prophylaxis; Anti-Retroviral; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• Median Genvoya plasma concentration

  Approximately 24 mL of blood will be drawn to obtain Genvoya plasma concentration (median + range; ng/mL)

  2 to up to 96 hours after time of dose

• Median Darunavir plasma concentration

  Approximately 24 mL of blood will be drawn to obtain Darunavir plasma concentration (median + range; ng/mL)

  2 to up to 96 hours after time of dose

• Median Genvoya rectal tissue distribution

  Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Genvoya rectal tissue distribution (median + range; ng/mg of tissue).

  2 to up to 96 hours after time of dose

• Median Darunavir rectal tissue distribution

  Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Darunavir rectal tissue distribution (median + range; ng/mg of tissue).

  2 to up to 96 hours after time of dose

Secondary Outcomes (4)

• Median Genvoya rectal secretion concentration

  2 to up to 96 hours after time of dose

• Median Darunavir rectal secretion concentration

  2 to up to 96 hours after time of dose

• Median Genvoya urethral secretion concentration

  2 to up to 96 hours after time of dose

• Median Darunavir urethral secretion concentration

  2 to up to 96 hours after time of dose

Study Arms (8)

Pre- drug

NO INTERVENTION

Participants will not receive any drug. They will be asked to return 1-6 weeks after the screening visit for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, rectal swabs, urine sample, and rectal biopsy via rigid sigmoidoscopy.

Group A.1

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 2 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group A.2

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 24 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group A.3

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 72 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group B.1

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 4 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group B.2

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 48 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group B.3

EXPERIMENTAL

Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 96 hours after dosing.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Group C

EXPERIMENTAL

Participants will be given a one- day supply of with Genvoya and Darunavir®. Participants return 8 hours (+/- 30min window), 24 hours (+/- 1 hr), and 48 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 8 hours after taking the medication.

Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Interventions

Single dose of Genvoya® and a single 800 mg dose of Darunavir® DRUG

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Group A.1; Group A.2; Group A.3; Group B.1; Group B.2; Group B.3; Group C

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-negative man who reports receptive anal sex with another man in the last 6 months
• Aged 18-49 years
• Not currently taking PrEP and no plans to initiate during study
• Not currently taking PEP
• Able to provide informed consent in English
• No plans for relocation in the next 3 months
• Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling
• Willing to use study products as directed
• Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure.

You may not qualify if:

• History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
• Significant laboratory abnormalities at baseline visit, including but not limited to:
• Hgb ≤ 10 g/dL
• PTT \> 1.5x ULN or INR \> 1.5x ULN
• Platelet count \<100,000
• Creatinine clearance \<60
• Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:
• Uncontrolled or severe cardiac arrhythmia
• Recent major abdominal, cardiothoracic, or neurological surgery
• History of uncontrolled bleeding diathesis
• History of colonic, rectal, or vaginal perforation, fistula, or malignancy
• History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement
• Continued need for, or use during the 14 days prior to enrollment, of the following medications:
• Aspirin or more than 4 doses of NSAIDs
• Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents

Sponsors & Collaborators

• Emory University: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Colleen Kelley, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 21, 2018
• Study Start: April 27, 2018
• Primary Completion: March 29, 2019
• Study Completion: March 29, 2019
• Last Updated: August 28, 2020

Record last verified: 2020-08

Locations

US (1)