Clinical trial NCT03282799: Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women
Official title: Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV/AIDS
Contraception
Keywords: etonogestrel
efavirenz
antiretroviral therapy
HIV
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Infectious Disease Institute, Kampala, Uganda
name: University of Nebraska
First posted: 2017-09-14
Enrollment: 72
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected Ugandan women on efavirenz-based antiretroviral therapy using either a single etonogestrel implant or two etonogestrel implants for at least one year.

Detailed description: This study is being done to compare the rate of ovulation when women receive two subdermal implant contraception devices containing the hormone etonogestrel (instead of only one device) while taking the HIV drug efavirenz. The etonogestrel implant is a device that is inserted under the skin on the upper arm and releases a small amount of drug into the body every day over a long period of time to prevent pregnancy for 3 years. A total of 72 non-pregnant women in Uganda, who agree to use the copper intrauterine device throughout the study, will participate in this study. Half will be assigned by chance to use one implant and half will be assigned to use two implants at the entry visit. After the entry visit to place the implant, visits will be scheduled 1 week, 4 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 21 weeks, 22, weeks, 23 weeks, 24 weeks, 36 weeks, 45 weeks, 46 weeks, 47 weeks, and 48 weeks after the implant(s) were placed. The rate of ovulation (determined by weekly endogenous progesterone concentrations in the blood during months 3, 6, and 12) will be compared between women that receive two 68 mg etonogestrel implants compared to one 68 mg etonogestrel implant in combination with efavirenz-based antiretroviral therapy. Cervical mucus quality (from cervical mucus samples collected weekly at months 3, 6, and 12), the blood concentration of etonogestrel (from blood samples collected at day 3 and weeks 1, 4, 12, 24, 36, 48) and efavirenz (from blood samples collected at enrollment and weeks 4, 12, 24, 36, 48, and the number of adverse events deemed related to etonogestrel implant use through 48 weeks will also be compared between the one- and two-implant study arms.

Eligibility criteria: Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Women aged 18 years to 40 years.
4. Diagnosed with HIV infection.
5. Medically eligible for the etonogestrel subdermal implant as a contraceptive method.
6. Receiving efavirenz-based anti-retroviral therapy for a minimum of 3 months prior to screening.
7. Must agree to have concurrent highly effective non-hormonal contraception with a copper intrauterine device, if not previously medically sterilized.
8. Participants must report regular menses (bleeding for 4-8 days at 21- to 35-day intervals) for the preceding 2 months.
9. Participants must have a negative urine pregnancy test at entry and report no unprotected sex since the last menstrual period or in the last two weeks.

Exclusion Criteria:

1. HIV RNA \> 50 copies/mL at screening visit.
2. Serum hemoglobin \< 10.0 g/dL.
3. Elevations in serum levels of alanine transaminase above 5 times the upper limit of normal.
4. Elevations in serum creatinine above 2.5 times the upper limit of normal.
5. Use of drugs known to be contraindicated with etonogestrel or efavirenz within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, the study team will review all concomitant medications at screening for drug interactions with efavirenz and the etonogestrel implant.
6. Currently pregnant or postpartum less than 30 days at study entry.
7. Breastfeeding women within 6 months of delivery.
8. Use of hormonal contraception in the preceding 3 months prior to entry
9. Participants determined to be ineligible for intrauterine device placement.
10. Patients with a history of hypersensitivity to etonogestrel implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.
11. Presence of any active clinically significant disease or life-threatening disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.

Primary outcomes:
measure: Proportion of Participants That Ovulate During Month 3
timeFrame: 3 months
measure: Proportion of Participants That Ovulate During Month 6
timeFrame: 6 months
measure: Proportion of Participants That Ovulate During Month 12
timeFrame: 12 months
Secondary outcomes:
measure: Proportion of Cervical Mucus Scores Greater Than 10
timeFrame: 12 months
measure: Median Efavirenz Concentration at Enrollment
timeFrame: Day 0
measure: Median Efavirenz Concentration at Week 4
timeFrame: 4 weeks
measure: Median Efavirenz Concentration at Week 12
timeFrame: 12 weeks
measure: Median Efavirenz Concentration at Week 24
timeFrame: 24 weeks
measure: Median Efavirenz Concentration at Week 36
timeFrame: 36 weeks
measure: Median Efavirenz Concentration at Week 48
timeFrame: 48 weeks
measure: Median Etonogestrel Concentration at Week 1
timeFrame: 1 week
measure: Median Etonogestrel Concentration at Week 4
timeFrame: 4 weeks
measure: Median Etonogestrel Concentration at Week 12
timeFrame: 12 weeks
measure: Median Etonogestrel Concentration at Week 24
timeFrame: 24 weeks
measure: Median Etonogestrel Concentration at Week 36
timeFrame: 36 weeks
measure: Median Etonogestrel Concentration at Week 48
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infectious Disease Institute
Study officials:
affiliation: University of Pittsburgh
name: Catherine A Chappell, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: