Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Proportion of Participants That Ovulate During Month 3
研究概览
简要总结
This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected women on efavirenz (EFV)-based antiretroviral therapy (ART) using either a single etonogestrel (ENG) implant or two ENG implants for at least one year.
详细描述
Due to drug-drug interactions between efavirenz (EFV) and progestins, HIV-infected women on EFV-based antiretroviral therapy (ART) and using the etonogestrel implant have significantly lower systemic ENG concentrations than HIV-infected women not on ART. This finding has raised concerns regarding the contraceptive efficacy of the ENG implant for women on EFV-based ART and clinical studies have an increased rate of pregnancies for women on EFV-based ART and using a contraceptive implant. This study a randomized, open-label, longitudinal pharmacodynamic study to compare frequency of ovulation between a control group of HIV-infected women on efavirenz-based antiretroviral therapy receiving standard dose etonogestrel (ENG) implant and a treatment group receiving increased dose ENG implant. The overall goal is to assess the pharmacodynamic significance of the known drug-drug interaction between EFV and ENG and to determine if the increased dose will overcome this interaction. Overall, this study will improve long-acting reversible contraceptive treatment options for women living with HIV and prevent unintended pregnancy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- •Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Women age 18 years to 40 years
- •Diagnosed with HIV infection
- •Medically eligible for the ENG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use20
- •Receiving EFV-based ART for a minimum of 3 months prior to screening
- •Must agree to have concurrent highly effective non-hormonal contraception with a copper IUD, if not previously medically sterilized.
- •Participants must report regular menses (bleeding for 4-8 days at 21 to 35 day intervals) for the preceding 2 month
- •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.
排除标准
- •HIV RNA > 50 copies/mL at screening visit
- •Serum hemoglobin < 10.0 g/dl
- •Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
- •Elevations in serum creatinine above 2.5 times the upper limit of normal
- •Use of drugs known to be contraindicated with ENG or EFV within 30 days of study entry. Due to the dynamic nature of drug interactions related to ART, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table45 and the ENG implant product labeling
- •Currently pregnant or postpartum <30 days at study entry.
- •Breastfeeding women within 6 months of delivery.
- •Use of hormonal contraception in the preceding 3 months prior to entry
- •Participants determined to be ineligible for IUD placement by the WHO Medical Eligibility Criteria for Contraceptive Use46
- •Patients with a history of hypersensitivity to ENG implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.
- •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.
研究组 & 干预措施
Standard Dose Etonogestrel Implant
Single 68 mg etonogestrel implant
干预措施: etonogestrel implant (Drug)
Increased Dose Etonogestrel Implant
Two 68 mg (136 mg total) etonogestrel implants
干预措施: etonogestrel implant (Drug)
结局指标
主要结局
Proportion of Participants That Ovulate During Month 3
时间窗: 3 months
Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
Proportion of Participants That Ovulate During Month 6
时间窗: 6 months
Proportion of participants that experience at least one ovulation during month 6 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 6 (weeks 21-24). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
Proportion of Participants That Ovulate During Month 12
时间窗: 12 months
Proportion of participants that experience at least one ovulation during month 12 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 12 (weeks 45-48). Ovulation is defined as endogenous progesterone concentrations of \>3 ng/mL.
次要结局
- Median Efavirenz Concentration at Enrollment(Day 0)
- Proportion of Cervical Mucus Scores Greater Than 10(12 months)
- Median Efavirenz Concentration at Week 4(4 weeks)
- Median Efavirenz Concentration at Week 12(12 weeks)
- Median Efavirenz Concentration at Week 24(24 weeks)
- Median Efavirenz Concentration at Week 36(36 weeks)
- Median Efavirenz Concentration at Week 48(48 weeks)
- Median Etonogestrel Concentration at Week 1(1 week)
- Median Etonogestrel Concentration at Week 4(4 weeks)
- Median Etonogestrel Concentration at Week 12(12 weeks)
- Median Etonogestrel Concentration at Week 24(24 weeks)
- Median Etonogestrel Concentration at Week 36(36 weeks)
- Median Etonogestrel Concentration at Week 48(48 weeks)
研究者
Catherine Anne Chappell
Assistant Professor
University of Pittsburgh