Pharmacokinetics of 1% Tenofovir Gel Following CoitusPhase 1NCT01687205
Coital Pharmacokinetics/Pharmacodynamics (PK/PD) of Tenofovir Gel
A Phase 1 study testing 1% Tenofovir Gel in people with Pharmacokinetics of 1% Tenofovir Gel Following Coitus and Pharmacodynamics of 1% Tenofovir Gel Following Coitus, run by CONRAD at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 46 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of 1% Tenofovir Gel Following Coitus, Pharmacodynamics of 1% Tenofovir Gel Following Coitus
- What is being tested?
- 1% Tenofovir Gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2012to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 46 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women must meet the following criteria to be eligible for inclusion in the study:
- 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
Show all 23Show fewer
- 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
- Per participant report, regular menstrual cycles with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera)
- Note: This criterion is not applicable to participants using continuous combination oral contraceptive pills, as the absence of regular menstrual cycles is an expected, normal consequence in this context.
- Anatomy sufficient for performing pelvic examinations and for collecting vaginal and cervical specimens
- Female participants must also agree to abstain from intercourse (oral, anal, or penile-vaginal) and other vaginal practices (e.g., masturbation, douching, tampon use, application of lubricants/spermicides or other related practices) 72 hours prior to each follow-up visit.
- Men must also meet the following criteria:
- Age 21 or older at Screening, verified per site SOPs
- Agree to abstain from intercourse (oral, anal, or penile-vaginal) and other penile practices (e.g., masturbation, application of lubricants/spermicides or other related practices) 72 hours prior to each follow-up visit.
Who cannot join
- 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
Show all 35Show fewer
- 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
- Note: For female participants, cervical bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the IoR/designee is considered expected non-menstrual bleeding and is not exclusionary.
- Note: Otherwise eligible participants with exclusionary genital findings may be enrolled after the findings have improved to a non-exclusionary severity grading or resolved as long as treatment is completed and all symptoms have resolved within 30 days of obtaining informed consent for Screening/Enrollment.
- 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
- Women who meet any of the following criteria will be excluded from the study:
- Participant report (or clinical finding) of the following:
- Last pregnancy outcome 90 days or less prior to Enrollment
- Currently pregnant
- Note: Self-reported pregnancy is adequate for exclusion from the study. A documented negative pregnancy test performed by study staff is required for inclusion.
- Currently breastfeeding
- Intends to become pregnant in the next 4 months
- Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage) within the prior 30 days to Enrollment
- Note: This does not include biopsy for the evaluation of an abnormal pap result or endometrial biopsy that occurred more than 7 days prior to Enrollment.
- Any of the following laboratory abnormalities at Screening:
- Hemoglobin less than 10.0 g/dl
- Platelet count less than 100,000/mm3
- Note: Otherwise eligible participants with an exclusionary test may be re-tested during the screening process
- Use of a vaginal douche or other intravaginal products (excluding tampon use) in the 30 days prior to Enrollment
- Currently menopausal or perimenopausal
- Men who meet any of the following criteria will be excluded from the study:
- Participant report of penile procedures (e.g. biopsy, circumcision) within 42 days prior to Enrollment
- For uncircumcised men, per participant report, treatment of candidal balanoposthitis/ balanitis within 30 days prior to Enrollment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Case Western Reserve University
Cleveland, Ohio, 44106
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase 1 Evaluation of the Impact of Coitus on Pharmacokinetics and Pharmacodynamics of Tenofovir 1% Gel Following Pericoital or Daily Gel Dosing
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
Read more
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
- Being tested
- 1% Tenofovir Gel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1% Tenofovir GelDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Single Dose/1 hour before and 1 hour after sex (BAT) Cohort Receives: Drug: 1% Tenofovir Gel |
| Group 2 | Active comparator | Multiple Dose Cohort Receives: Drug: 1% Tenofovir Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Visits 2b, 3b, 4b, 5b, 6b and 7b.
Secondary outcomes (1)
Acceptability
To assess the acceptability of the MTN-011 trial to male and female participants
Measured: Visit 7b.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2012 (estimated)
- Study startNov 2012
- Primary completionJun 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pharmacokinetics of 1% Tenofovir Gel Following CoitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Betsy Herold, MD, Study chair, Albert Einstein College of MedicineBeatrice A. Chen, MD, MPH, Principal investigator, University of PittsburghRobert A. Salata, MD, Principal investigator, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687205
- Sponsor's protocol ID
- MTN-011
- Other IDs
- 3UM1AI068633, UM1AI068615, 11825
- Status last verified
- Jun 2021
- First submitted
- 27 Aug 2012
- Last updated
- 28 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26508513
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Evaluation of the Impact of Coitus on Pharmacokinetics and Pharmacodynamics of Tenofovir 1% Gel Following Pericoital or Daily Gel Dosing
- ClinicalTrials.gov ID
- NCT01687205
- Acronym / sponsor ID
- MTN-011
- Conditions
- Pharmacokinetics of 1% Tenofovir Gel Following Coitus, Pharmacodynamics of 1% Tenofovir Gel Following Coitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Nov 2012
- Primary completion
- Jun 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 18 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: 1% Tenofovir GelSingle Dose/1 hour before and 1 hour after sex (BAT) Cohort |
| Group 2 | Active comparator | Drug: 1% Tenofovir GelMultiple Dose Cohort |
Who may qualify
- Ages
- 21 to 46 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Able and willing to provide the following:
- Per participant report, at low risk for HIV/STI. Low risk is defined as:
- 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
Key exclusion criteria (35 listed)
- Men and women who meet any of the following criteria will be excluded from the study.
- Participant report of any of the following:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1% Tenofovir Gel | Drug | Group 1, Group 2 |
Primary outcome
Pharmacokinetics of tenofovir 1% gel
Time frame: Visits 3b, 4b, 5b, 6b and 7b.
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
Pharmacodynamics of luminal drug
Time frame: Visits 2b, 3b, 4b, 5b, 6b and 7b.
To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples
1 secondary outcome
Acceptability
Time frame: Visit 7b.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2021.
- Results publication: PubMed 26508513Herold 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Betsy Herold, MD study chair
Albert Einstein College of Medicine
Beatrice A. Chen, MD, MPH principal investigator
University of Pittsburgh
Robert A. Salata, MD principal investigator
Case Western Reserve University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 1% Tenofovir Gel in people with Pharmacokinetics of 1% Tenofovir Gel Following Coitus and Pharmacodynamics of 1% Tenofovir Gel Following Coitus, run by CONRAD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of tenofovir 1% gel (time frame: Visits 3b, 4b, 5b, 6b and 7b.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01687205, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2021.