Coital Pharmacokinetics/Pharmacodynamics (PK/PD) of Tenofovir Gel

NCT01687205 | Completed Phase 1 DMC

• 4 other identifiers: MTN-0113UM1AI068633UM1AI06861511825
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

Study Objectives:

• To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel in female genital tract secretions, vaginal and cervical tissue and rectal tract secretions
• To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples Study Summary: MTN-011 will enroll heterosexual monogamous, sexually active couples, in which both partners are healthy and HIV-negative. The female participants must be between the ages of 21-46 (inclusive) and currently using effective non-barrier contraception. Male participants must be 21 years of age or older. This Phase 1 expanded safety study will assess tenofovir PK in the genital tract secretions (CVL), rectal (rectal sponge) and both intracellular and extracellular tissue compartments (vaginal biopsy) in the absence of, or following coitus. Pharmacodynamics (antiviral activity) will also be assessed in CVL. MTN-011 will study the timing in which coitus might have the greatest impact on these variables, which is when gel is applied shortly prior to coitus in the absence of a drug reservoir. MTN-011 will examine PK/PD in response to a single dose of 1% tenofovir gel applied shortly before sex and compare to PK/PD assessments following a single gel application without sex. Additionally, data obtained from a visit in which participants do not dose with gel and do not have sex will serve as an additional control for the pharmacodynamic (PD) studies of the antiviral activity in CVL. If tenofovir retains its antiviral activity following sex, then the anti-HIV activity in CVL collected at the visit in which female participants dose with gel and have sex should be comparable to that of CVL collected at the visit in which females dose with gel and then do not engage in intercourse and significantly greater than the endogenous anti-HIV activity in CVL obtained at the visit in which participants do not dose with gel but do have sex and the visit in which no gel is administered and sex does occur. Data analysis performed after the completion of enrollment and follow-up procedures will demonstrate if there is an impact of coitus and semen on PK/PD when a single 1% tenofovir dose is applied shortly prior to sex.

Conditions

Pharmacokinetics of 1% Tenofovir Gel Following Coitus; Pharmacodynamics of 1% Tenofovir Gel Following Coitus

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics of tenofovir 1% gel

  To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel in female genital tract secretions, vaginal and cervical tissue and rectal tract secretions

  Visits 3b, 4b, 5b, 6b and 7b.

• Pharmacodynamics of luminal drug

  To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples

  Visits 2b, 3b, 4b, 5b, 6b and 7b.

Secondary Outcomes (1)

• Acceptability

  Visit 7b.

Other Outcomes (3)

• Impact of coitus and/or tenofovir on the genital tract mucosal environment

  Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.

• Semen biomarker

  Visits 1, 2b, 3b, 5b and 7b.

• Retained drug levels in the lumen

  Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Single Dose/1 hour before and 1 hour after sex (BAT) Cohort

Drug: 1% Tenofovir Gel

Group 2

ACTIVE COMPARATOR

Multiple Dose Cohort

Drug: 1% Tenofovir Gel

Interventions

1% Tenofovir Gel DRUG

Group 1; Group 2

Eligibility Criteria

• Age: 21 Years - 46 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide the following:
• Written informed consent to be screened for and take part in the study
• Adequate locator information, as defined in site SOPs
• Per participant report, at low risk for HIV/STI. Low risk is defined as:
• No sexually transmitted infections (STIs) in the 6 months prior to Screening
• No non-therapeutic intravenous drug use in the 18 months prior to Screening
• In a mutually monogamous relationship with a partner of the opposite sex for 6 months prior to Screening and the intent to stay in this relationship for the next 4 months
• At Screening and Enrollment, both partners independently report not using barrier contraception and/or barrier protection as part of normal coital routine and report the intent to continue said sexual practice for the duration of study participation
• HIV-uninfected based upon testing performed by study staff at Screening (per protocol algorithm)
• Agrees not to participate in other research studies involving drugs, medical devices, or genital and rectal products, or large blood draw studies during study participation
• Women must also meet the following criteria:
• Age 21 through 46 years (inclusive) at Screening, verified per site SOPs
• Pap result in the 12 calendar months prior to Screening consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009), or satisfactory evaluation with no treatment required of non-Grade 0 Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to the Screening Visit
• Note: Women with a documented normal result within the 12 months prior to screening need not have a Pap smear during the screening period. Women with abnormal Pap smears can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology). Need for a repeat Pap within 6 months does not preclude enrollment prior to that result becoming available.
• Must be currently using effective non-barrier contraception, other than a contraceptive vaginal ring, for at least three months prior to Screening (i.e., oral contraceptive, patch, injectable hormones, subdermal implants, intrauterine device, female or male sterilization) and intending to use this method for the course of the study

You may not qualify if:

• Men and women who meet any of the following criteria will be excluded from the study.
• Participant report of any of the following:
• Known allergy to the study product (ever)
• Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to Screening
• Participation in any other research study involving drugs, medical devices, or genital products 30 days or less prior to Enrollment
• Plans to relocate away from the study site in the next 4 months
• History of domestic violence with current partner (ever)
• Systemic or topical antimicrobials within the last 7 days prior to Enrollment
• Currently using or planning to use pharmacologic immune modulator(s)
• At Screening or Enrollment, symptomatic urinary tract infection (UTI)
• Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved as long as treatment is completed and all symptoms have resolved within 30 days of obtaining informed consent for Screening/Enrollment.
• At Screening, has a positive hepatitis B surface antigen (HBsAg) test result
• At Screening or Enrollment, has an STI or reproductive tract infection (RTI) requiring treatment per current Centers for Disease Control (CDC) guidelines
• Genital signs and/or symptoms of Grade 2 or higher
• Has any other condition that, in the opinion of the Investigator of Record (IoR)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Sponsors & Collaborators

• CONRAD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute of Mental Health (NIMH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Herold BC, Chen BA, Salata RA, Marzinke MA, Kelly CW, Dezzutti CS, McGowan I, Galaska B, Levy L, Piper JM, Hillier S, Hendrix CW. Impact of Sex on the Pharmacokinetics and Pharmacodynamics of 1% Tenofovir Gel. Clin Infect Dis. 2016 Feb 1;62(3):375-382. doi: 10.1093/cid/civ913. Epub 2015 Oct 27.

  PMID: 26508513 RESULT

Study Officials

• Betsy Herold, MD

  Albert Einstein College of Medicine

  STUDY CHAIR

• Beatrice A. Chen, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Robert A. Salata, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: September 18, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: November 1, 2014
• Last Updated: June 28, 2021

Record last verified: 2021-06

Locations

US (2)