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

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ClinicalTrials.gov Identifier: NCT03472963
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : May 3, 2018
Sponsor:
Collaborator:
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Colleen Kelley, Emory University

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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir® Phase 1

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  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Used for Future HIV Post-exposure Prophylaxis Regimens.
Actual Study Start Date : April 27, 2018
Estimated Primary Completion Date : January 15, 2019
Estimated Study Completion Date : January 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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




Primary Outcome Measures :
  1. Median Genvoya plasma concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Approximately 24 mL of blood will be drawn to obtain Genvoya plasma concentration (median + range; ng/mL)

  2. Median Darunavir plasma concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Approximately 24 mL of blood will be drawn to obtain Darunavir plasma concentration (median + range; ng/mL)

  3. Median Genvoya rectal tissue distribution [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Genvoya rectal tissue distribution (median + range; ng/mg of tissue).

  4. Median Darunavir rectal tissue distribution [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Darunavir rectal tissue distribution (median + range; ng/mg of tissue).


Secondary Outcome Measures :
  1. Median Genvoya rectal secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal swabs for Genvoya rectal secretion concentration (median + range; ng/swab)

  2. Median Darunavir rectal secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal swabs for Darunavir rectal secretion concentration (median + range; ng/swab)

  3. Median Genvoya urethral secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Urethral swab for Genvoya urethral secretion concentration (median + range; ng/swab)

  4. Median Darunavir urethral secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Urethral swab for Darunavir urethral secretion concentration (median + range; ng/swab)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472963


Contacts
Contact: Colleen Kelley, MD, MPH 404-712-1823 colleen.kelley@emory.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Colleen Kelley, MD, MPH    404-712-1823    colleen.kelley@emory.edu   
Sponsors and Collaborators
Emory University
Centers for Disease Control and Prevention
Investigators
Principal Investigator: Colleen Kelley, MD, MPH Emory University

Responsible Party: Colleen Kelley, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT03472963     History of Changes
Other Study ID Numbers: IRB00101179
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018

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

Keywords provided by Colleen Kelley, Emory University:
Post-Exposure Prophylaxis
Anti-Retroviral
Pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Anti-Retroviral Agents
Anti-HIV Agents
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents