HIV PreventionPhase 1NCT01421368
Contraception and Menstrual Cycle Effect on Pharmacokinetics, Pharmacodynamics and Safety in Tenofovir Vaginal Gel Use
A Phase 1 study testing Tenofovir 1% vaginal gel, Depo-medroxyprogesterone acetate (DMPA) and Oral contraceptive: LNG 150 mcg and EE 30 mcg in people with HIV Prevention, run by CONRAD at 3 sites in 2 countries.
Trial summary
The purpose of the study is to examine the effects of two contraceptive methods and the menstrual cycle on the pharmacokinetics, pharmacodynamics of tenofovir 1% gel and the effect of the contraceptive methods on markers of mucosal safety. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Prevention
- What is being tested?
- Tenofovir 1% vaginal gel, Depo-medroxyprogesterone acetate (DMPA) and Oral contraceptive: LNG 150 mcg and EE 30 mcg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Mar 2012to Mar 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 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to use OCs or DMPA
- General good health (by volunteer history and investigator assessment) without any clinically significant systemic disease
- Currently having regular menstrual cycles of 25 to 35 days by volunteer report
- History of Pap smears and follow-up consistent with American Congress of Obstetricians and Gynecologists (ACOG) practice bulletin #99 or #109 or willing to undergo a Pap smear at Visit 1
- Willing to follow protocol requirements including abstinence, use of study condoms, and prohibited use of intravaginal products
- Willing to follow post-biopsy restrictions for at least 5 days following genital biopsies
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- Meets one of the following criteria:
- Sexually abstinent and planning to remain abstinent for the duration of the study.
- In a mutually monogamous relationship for at least the last 4 months with a male partner who is at least 18 years of age, willing to use condoms, and has no known HIV infection or risks for sexually transmitted infections (STIs)
- In a mutually monogamous same-sex relationship for at least the last 4 months with a partner who is at least 18 years of age and has no known HIV infection or risks for STIs
- Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
- Negative urine pregnancy test
- Willing to give voluntary consent, sign an informed consent form and comply with study procedures, as required by the protocol
Who cannot join
- History of hysterectomy
- Currently pregnant or within 2 calendar months from the last pregnancy outcome. (Note: If recently pregnant must have had at least 2 spontaneous menses since pregnancy outcome.)
- Use of any hormonal contraceptive method in the last 30 days (oral, transdermal, transvaginal, implant, or hormonal intrauterine contraceptive device)
- Injection of DMPA in the last 6 months
- Protection from pregnancy by presence of a copper IUD
- Currently breastfeeding or having breastfed an infant in the last 2 months, or planning to breastfeed during the course of the study
Show all 22Show fewer
- History of sensitivity/allergy to any component of the study product, or topical anesthetic, or allergy to both silver nitrate and Monsel's solution
- Diagnosed with or treated for any STI or pelvic inflammatory disease in the last 6 months. (Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least 6 months may be considered for eligibility.)
- Positive test for Trichomonas vaginalis, Neisseria gonorrhoeae or Chlamydia trachomatis
- Symptomatic vulvovaginal candidiasis, Nugent score greater than or equal to 7 at screening or bacterial vaginosis (BV) at Visit 2, or urinary tract infection (UTI)
- Deep epithelial genital findings such as abrasions, ulcerations, or lacerations, or vesicles suspicious for STIs
- Positive test for HIV
- Positive test for Hepatitis B surface antigen (HBsAg)
- Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy
- Chronic or acute vulvar or vaginal symptoms (e.g., pain, irritation, or spotting)
- Contraindications to the chosen contraceptive method
- Known current drug or alcohol abuse which could impact study compliance
- Grade 1 or higher laboratory abnormality, per the August 2009 update of the DAIDS Table for Grading the Severity of Adverse Events
- Participation in any other investigational trial (device, drug, or vaginal trial) in the last 30 days or planned participation in any other investigational trial during the study
- History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix in the last 14 days
- Abnormal finding on laboratory or physical examination or a social or medical condition which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
- Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, antifungals, antivirals or antiretrovirals
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Easter Virginia Medical School
Norfolk, Virginia, 23507
University of Pittsburgh School of Medicine, Center for Family Planning Research
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Assessing the Effect of Contraception and the Menstrual Cycle on Pharmacokinetics, Pharmacodynamics, and Vaginal Safety in Tenofovir Vaginal Gel Users
The purpose of the study is to examine the effects of two contraceptive methods and the menstrual cycle on the pharmacokinetics, pharmacodynamics of tenofovir 1% gel and the effect of the contraceptive methods on markers of mucosal safety.
Read the detailed description
Each woman will be seen in 6 visits and will be contacted by two scheduled follow-up telephone calls/visits. Volunteers will be consented at Visit 1 and undergo procedures to assess whether they are eligible to continue in the study. At Visit 2 (cycle days 20-25), after it has been confirmed that the participant meets all of the inclusion criteria and none of the exclusion criteria, genital samples will be taken and she will be given 2 applicators of tenofovir 1% gel to insert two hours apart. She will be instructed to return for Visit 3, approximately 3 or 11 hours after insertion of the second gel, as determined by randomization. The participant will retain this sampling assignment throughout the study.
At Visit 3 (cycle days 20-25), blood and genital samples will be collected. The participant will again be given 2 applicators of tenofovir 1% gel to insert two hours apart. She will be instructed to return approximately 3 or 11 hours after insertion of the second gel for Visit 4 (cycle days 5-10) and blood and genital samples will be taken. The participant will then start the contraceptive method that she has chosen from the two methods being evaluated in the study.
Each participant will be contacted about 4-5 weeks after Visit 4 to confirm the next visit date (Visit 5).
Visit 5 will take place about 6 weeks after starting contraception and will not have an associated gel use. Follow-up genital samples will be collected at Visit 5. The participant will be given 2 applicators of tenofovir 1% gel to insert two hours apart prior to Visit 6.
Visit 6 will take place about 10 weeks after starting contraception. Follow-up blood and genital samples will be collected approximately 3 or 11 hours after insertion of the second gel.
Each participant also will have a follow-up call or visit approximately 1-2 weeks after Visit 6 to confirm that there have been no adverse experiences. If necessary, she may be seen in an unscheduled visit for follow-up. She will then be exited from the study.
- Conditions
- HIV Prevention
- Being tested
- Tenofovir 1% vaginal gel, Depo-medroxyprogesterone acetate (DMPA), Oral contraceptive: LNG 150 mcg and EE 30 mcg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir 1% vaginal gelDrug
Tenofovir 1% gel is supplied as a clear, transparent, viscous gel packaged in pre-filled single use applicators. Each applicator contains 4.0 mL of tenofovir gel (equal to 4.4 gm) at a concentration of 1% (weight for weight) formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben and hydroxyethylcellulose, and is pH adjusted to 4-5
Depo-medroxyprogesterone acetate (DMPA)Drug
Also called Depo-Provera
DMPA is an intramuscular injectable contraceptive containing 150 mg of medroxyprogesterone acetate. It is FDA approved for 12 weeks of use per injection.
Oral contraceptive: LNG 150 mcg and EE 30 mcgDrug
Each pill contains LNG 150 mcg (the active levorotatory enantiomer of norgestrel) and EE 30 mcg. Each pack contains 21 active pills and 7 placebo pills
| Study group | Role | What they receive |
|---|---|---|
| DMPA and tenofovir 1% gel | Experimental | Not described Receives: Drug: Tenofovir 1% vaginal gel; Drug: Depo-medroxyprogesterone acetate (DMPA) |
| Oral contraceptive and tenofovir 1% gel | Experimental | Not described Receives: Drug: Tenofovir 1% vaginal gel; Drug: Oral contraceptive: LNG 150 mcg and EE 30 mcg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of oral contraceptives and DMPA on tenofovir PK, PD, and safety by comparing the following endpoints before initiation of contraceptive method and 10 weeks after initiation of contraceptive method
- composite of pharmacokinetics for TFV in plasma, vaginal aspirate \& genital tissue
- composite of pharmacokinetics for TFV-DP in PBMCs, endocervical cells \& genital tissue
- rates of HIV-1 infection in an explant challenge assay (one site only)
- immune cell activation \& mucosal histology in genital tissue
- genitourinary AEs
Measured: 3 and 11 hours after insertion of 2 doses of study gel
Secondary outcomes (2)
Effect of the menstrual cycle of the tenofovir PK, PD, and safety by comparing the following endpoints 3 and 1 hours after insertion of 2 doses of study gel, in the follicular and luteal phases before initiating contraception
- composite of pharmacokinetics for TFV in plasma, vaginal aspirate \& genital tissue
- composite of pharmacokinetics for TFV-DP in PBMCs, endocervical cells \& genital tissue
- rates of HIV-1 infection in an explant challenge assay (one site only)
- immune cell activation \& mucosal histology in genital tissue
- genitourinary AEs
Measured: 3 and 11 hours after insertion of 2 doses of study gel
To assess the effect of oral contraceptives and DMPA on markers of mucosal immunity by comparing the following endpoints (in the absence of tenofovir) before initiation of contraceptive method and 10 weeks after initiation of contraceptive method
- soluble immune markers in the CVL supernatant
- anti-HIV and anti-HSV in CVL
- immune cell characterization in the CVL cell pellet
- immune cell activation and mucosal histology in genital tissue
- rates of HIV-1 infection in an explant challenge assay (one site only)
- vaginal microflora
- genitourinary AEs
Measured: Before (baseline) and 10 weeks after contraceptive method start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2011 (estimated)
- Study startMar 2012
- Primary completionMar 2014
- Study completionMar 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 HIV PreventionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christine K. Mauck, M.D., Study director, CONRAD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01421368
- Sponsor's protocol ID
- A10-114
- Status last verified
- Apr 2015
- First submitted
- 9 Aug 2011
- Last updated
- 10 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Zalenskaya IA, Chandra N, Yousefieh N, Fang X, Adedipe OE, Jackson SS, Anderson SM, Mauck CK, Schwartz JL, Thurman AR, Doncel GF. Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity. J Clin Invest. 2018 Oct 1;128(10):4622-4638. doi: 10.1172/JCI120583. Epub 2018 Sep 17.
PubMed 30222141
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Effect of Contraception and the Menstrual Cycle on Pharmacokinetics, Pharmacodynamics, and Vaginal Safety in Tenofovir Vaginal Gel Users
- ClinicalTrials.gov ID
- NCT01421368
- Acronym / sponsor ID
- A10-114
- Conditions
- HIV Prevention
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 22 Aug 2011 (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.
The purpose of the study is to examine the effects of two contraceptive methods and the menstrual cycle on the pharmacokinetics, pharmacodynamics of tenofovir 1% gel and the effect of the contraceptive methods on markers of mucosal safety.
Detailed description
Each woman will be seen in 6 visits and will be contacted by two scheduled follow-up telephone calls/visits. Volunteers will be consented at Visit 1 and undergo procedures to assess whether they are eligible to continue in the study. At Visit 2 (cycle days 20-25), after it has been confirmed that the participant meets all of the inclusion criteria and none of the exclusion criteria, genital samples will be taken and she will be given 2 applicators of tenofovir 1% gel to insert two hours apart. She will be instructed to return for Visit 3, approximately 3 or 11 hours after insertion of the second gel, as determined by randomization. The participant will retain this sampling assignment throughout the study.
At Visit 3 (cycle days 20-25), blood and genital samples will be collected. The participant will again be given 2 applicators of tenofovir 1% gel to insert two hours apart. She will be instructed to return approximately 3 or 11 hours after insertion of the second gel for Visit 4 (cycle days 5-10) and blood and genital samples will be taken. The participant will then start the contraceptive method that she has chosen from the two methods being evaluated in the study.
Each participant will be contacted about 4-5 weeks after Visit 4 to confirm the next visit date (Visit 5).
Visit 5 will take place about 6 weeks after starting contraception and will not have an associated gel use. Follow-up genital samples will be collected at Visit 5. The participant will be given 2 applicators of tenofovir 1% gel to insert two hours apart prior to Visit 6.
Visit 6 will take place about 10 weeks after starting contraception. Follow-up blood and genital samples will be collected approximately 3 or 11 hours after insertion of the second gel.
Each participant also will have a follow-up call or visit approximately 1-2 weeks after Visit 6 to confirm that there have been no adverse experiences. If necessary, she may be seen in an unscheduled visit for follow-up. She will then be exited from the study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DMPA and tenofovir 1% gel | Experimental | Drug: Tenofovir 1% vaginal gel, Drug: Depo-medroxyprogesterone acetate (DMPA) |
| Oral contraceptive and tenofovir 1% gel | Experimental | Drug: Tenofovir 1% vaginal gel, Drug: Oral contraceptive: LNG 150 mcg and EE 30 mcg |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Willing and able to use OCs or DMPA
- General good health (by volunteer history and investigator assessment) without any clinically significant systemic disease
- Currently having regular menstrual cycles of 25 to 35 days by volunteer report
- History of Pap smears and follow-up consistent with American Congress of Obstetricians and Gynecologists (ACOG) practice bulletin #99 or #109 or willing to undergo a Pap smear at Visit 1
- Willing to follow protocol requirements including abstinence, use of study condoms, and prohibited use of intravaginal products
Key exclusion criteria (22 listed)
- History of hysterectomy
- Currently pregnant or within 2 calendar months from the last pregnancy outcome. (Note: If recently pregnant must have had at least 2 spontaneous menses since pregnancy outcome.)
- Use of any hormonal contraceptive method in the last 30 days (oral, transdermal, transvaginal, implant, or hormonal intrauterine contraceptive device)
- Injection of DMPA in the last 6 months
- Protection from pregnancy by presence of a copper IUD
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 |
|---|---|---|
| Tenofovir 1% vaginal gelTenofovir 1% gel is supplied as a clear, transparent, viscous gel packaged in pre-filled single use applicators. Each applicator contains 4.0 mL of tenofovir gel (equal to 4.4 gm) at a concentration of 1% (weight for weight) formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben and hydroxyethylcellulose, and is pH adjusted to 4-5 | Drug | DMPA and tenofovir 1% gel, Oral contraceptive and tenofovir 1% gel |
| Depo-medroxyprogesterone acetate (DMPA)Also: Depo-ProveraDMPA is an intramuscular injectable contraceptive containing 150 mg of medroxyprogesterone acetate. It is FDA approved for 12 weeks of use per injection. | Drug | DMPA and tenofovir 1% gel |
| Oral contraceptive: LNG 150 mcg and EE 30 mcgEach pill contains LNG 150 mcg (the active levorotatory enantiomer of norgestrel) and EE 30 mcg. Each pack contains 21 active pills and 7 placebo pills | Drug | Oral contraceptive and tenofovir 1% gel |
Primary outcome
Effect of oral contraceptives and DMPA on tenofovir PK, PD, and safety by comparing the following endpoints before initiation of contraceptive method and 10 weeks after initiation of contraceptive method
Time frame: 3 and 11 hours after insertion of 2 doses of study gel
* composite of pharmacokinetics for TFV in plasma, vaginal aspirate \& genital tissue * composite of pharmacokinetics for TFV-DP in PBMCs, endocervical cells \& genital tissue * rates of HIV-1 infection in an explant challenge assay (one site only) * immune cell activation \& mucosal histology in genital tissue * genitourinary AEs
2 secondary outcomes
Effect of the menstrual cycle of the tenofovir PK, PD, and safety by comparing the following endpoints 3 and 1 hours after insertion of 2 doses of study gel, in the follicular and luteal phases before initiating contraception
Time frame: 3 and 11 hours after insertion of 2 doses of study gel
To assess the effect of oral contraceptives and DMPA on markers of mucosal immunity by comparing the following endpoints (in the absence of tenofovir) before initiation of contraceptive method and 10 weeks after initiation of contraceptive method
Time frame: Before (baseline) and 10 weeks after contraceptive method start
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 10 Apr 2015.
- Derived from this study: PubMed 30222141Zalenskaya IA, Chandra N, Yousefieh N, Fang X, Adedipe OE, Jackson SS, Anderson SM, Mauck CK, Schwartz JL, Thurman AR, Doncel GF. Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity. J Clin Invest. 2018 Oct 1;128(10):4622-4638. doi: 10.1172/JCI120583. Epub 2018 Sep 17.
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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.
Christine K. Mauck, M.D. study director
CONRAD
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tenofovir 1% vaginal gel, Depo-medroxyprogesterone acetate (DMPA) and Oral contraceptive: LNG 150 mcg and EE 30 mcg in people with HIV Prevention, run by CONRAD at 3 sites in 2 countries.
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 13 inclusion and 22 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 10 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Dominican Republic. 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?
Effect of oral contraceptives and DMPA on tenofovir PK, PD, and safety by comparing the following endpoints before initiation of contraceptive method and 10 weeks after initiation of contraceptive method (time frame: 3 and 11 hours after insertion of 2 doses of study gel). 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 NCT01421368, 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 10 Apr 2015.