Body Compartment Pharmacokinetics of Anti- Retroviral Agents That May be Used for Future HIV Post- Exposure Prophylaxis. (PEP2)

Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Used for Future HIV Post-exposure Prophylaxis Regimens.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Detailed Description

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of MSM acquire HIV after exposure to the rectal mucosa through unprotected receptive anal intercourse. Post-exposure-prophylaxis (PEP) is an intervention that is used to prevent HIV infection soon (72 hours) after a potential exposure. HIV-negative people with a possible exposure to HIV are instructed to take 28 days of a combination anti-HIV medication regimen, Truvada® + Raltegravir. This study is being conducted to determine if the uptake of other anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues. These other medications might be considered for PEP regimens in the future.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. HIV-negative man who reports receptive anal sex with another man in the last 6 months
2. Aged 18-49 years
3. Not currently taking PrEP and no plans to initiate during study
4. Not currently taking PEP
5. Able to provide informed consent in English
6. No plans for relocation in the next 3 months
7. Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling
8. Willing to use study products as directed
9. 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.

Exclusion Criteria:

1. 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

2. Significant laboratory abnormalities at baseline visit, including but not limited to:

   1. Hgb ≤ 10 g/dL
   2. PTT > 1.5x ULN or INR > 1.5x ULN
   3. Platelet count <100,000
   4. Creatinine clearance <60

3. 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:

   1. Uncontrolled or severe cardiac arrhythmia
   2. Recent major abdominal, cardiothoracic, or neurological surgery
   3. History of uncontrolled bleeding diathesis
   4. History of colonic, rectal, or vaginal perforation, fistula, or malignancy
   5. History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement

4. Continued need for, or use during the 14 days prior to enrollment, of the following medications:

   1. Aspirin or more than 4 doses of NSAIDs
   2. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
   3. Any form of rectally administered agent besides lubricants or douching used for sexual intercourse

5. Continued need for, or use during the 90 days prior to enrollment, of the following medications:

   1. Systemic immunomodulatory agents
   2. Supraphysiologic doses of steroids
   3. Experimental medications, vaccines, or biologicals
6. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures
7. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
8. Current use of hormonal therapy
9. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Pre- drug; 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.
Experimental: Group A.1; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group A.2; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group A.3; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group B.1; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group B.2; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group B.3; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral
Experimental: Group C; 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®; Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Genvoya rectal secretion concentration	Rectal swabs for Genvoya rectal secretion concentration (median + range; ng/swab)	2 to up to 96 hours after time of dose
Median Darunavir rectal secretion concentration	Rectal swabs for Darunavir rectal secretion concentration (median + range; ng/swab)	2 to up to 96 hours after time of dose
Median Genvoya urethral secretion concentration	Urethral swab for Genvoya urethral secretion concentration (median + range; ng/swab)	2 to up to 96 hours after time of dose
Median Darunavir urethral secretion concentration	Urethral swab for Darunavir urethral secretion concentration (median + range; ng/swab)	2 to up to 96 hours after time of dose

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Centers for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): March 29, 2019
• Study Completion (Actual): March 29, 2019

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Anti-Retroviral; Post-Exposure Prophylaxis
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Darunavir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: IRB00101179

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No