A Pharmacokinetic Evaluation of Levonorgestrel Implant in HIV-Infected Women on Darunavir Versus Rilpivirine-based Antiretroviral Therapy
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Levonorgestrel concentrations: Change in mean levonorgestrel (LNG) concentrations
研究概览
简要总结
This study will evaluate the pharmacokinetic properties of Rilpivirine and Darunavir when used in combination with Levonorgestrel
详细描述
Despite the benefits of hormonal contraceptives, significant drug-drug interactions (DDIs) with some antiretroviral therapies (ART) represent a barrier to effective family planning methods for HIV-infected women. It is therefore critical to generate data on the combined use of hormonal contraceptives and ART. This study is a prospective, non-randomized, open-label, parallel, two-group, sparse-sampling pharmacokinetic (PK) study to describe levonorgestrel (LNG) PK parameters in two treatment groups (rilpivirine or darunavir- based ART) in 60 HIV-1 infected women. The primary endpoint is the comparison of the mean LNG concentrations at month 6 between the rilpivirine or darunavir treatment groups versus historical controls. This study will provide information on effective ART options for HIV positive women who opt for the contraceptive implant as a family planning method of choice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 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 45 years
- •Diagnosed with HIV infection
- •Medically eligible for the LNG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use11
- •Receiving EFV- or LPV/r-based ART for a minimum of 1 year
- •If not abstinent, must agree to use an effective non-hormonal method of contraception for the duration of the study including male and female condoms or the copper-T intrauterine device.
- •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 greater than 50 copies/mL at the screening visit
- •CD4 count below 200 cells/mm3 at the screening visit
- •History of virologic failure on the current regimen (two consecutive viral load results equal to or greater than 400 copies/mL)
- •Serum hemoglobin less than 9.0 g/dl at screening
- •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 LNG, RPV (for women taking EFV-based ART), or DRV (for women taking LPV-based ART) 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 based on the US Department of Health and Human Services drug interaction table 14 and the University of Liverpool HIV drug interaction tables (www.hiv-druginteractions.org)
- •Currently pregnant or postpartum <30 days at study entry.
- •Breastfeeding women within 6 months of delivery.
- •Patients with a history of hypersensitivity to LNG 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
Rilpivirine arm
All subjects will be administered oral rilpivirine 25mg once daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
干预措施: Rilpivirine (Drug)
Rilpivirine arm
All subjects will be administered oral rilpivirine 25mg once daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
干预措施: Levonorgestrel two rod sub-dermal implant (Drug)
Darunavir arm
All subjects will be administered oral darunavir/ritonavir 600/100mg twice daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
干预措施: Levonorgestrel two rod sub-dermal implant (Drug)
Darunavir arm
All subjects will be administered oral darunavir/ritonavir 600/100mg twice daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
干预措施: Darunavir+Ritonavir (Drug)
结局指标
主要结局
Levonorgestrel concentrations: Change in mean levonorgestrel (LNG) concentrations
时间窗: 6 months
Comparison of the mean levonorgestrel (LNG) concentrations at month 6 between the rilpivirine (RPV) or darunavir (DRV) treatment groups versus historical controls
次要结局
- Adverse events(12 months)
- Change in mean rilpivirine concentration(12 months)
- Change in mean darunavir concentration(12 months)
研究者
Infectious Diseases Institute
Head of Department, Prevention Care and Treatment Infectious Diseases Institute, Makerere University College of Health Sciences
Makerere University