Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant

Study Overview
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Brief Summary
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This study will evaluate the pharmacokinetic properties of rilpivirine and darunavir when used in combination with etonogestrel

Detailed Description
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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 study to describe etonogestrel (ENG) pharmacokinetic (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 ENG 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.

Official Title
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A Pharmacokinetic Evaluation of Etonogestrel Implant in HIV-infected Women on Darunavir Versus Ripilvirine-based Antiretroviral Therapy

Conditions
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HIV, Contraception

Intervention / Treatment
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* Drug: Etonogestrel 68Mg Implant
* Drug: rilpivirine
* Drug: darunavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 ENG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use 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. - Exclusion Criteria: 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 ENG, 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 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 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. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, non-randomized, open-label, parallel, two-group, sparse-sampling pharmacokinetic study to describe etonogestrel (ENG) pharmacokinetic parameters in two treatment groups (rilpivirine or darunavir- based antiretroviral therapy) in 60 HIV-1 infected women. The primary endpoint is the comparison of the mean ENG concentrations at month 6 between the rilpivirine or darunavir treatment groups versus historical controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ripivirine arm<br>All subjects will be administered oral ripilvirine 25mg once daily together with the rest of their oral antiretroviral combination and an etonogestrel single-rod subdermal implant (68mg/rod). Study participants will have both interventions for a period of one year. | Drug: Etonogestrel 68Mg Implant<br>* Etonogestrel single-rod subdermal implant (68mg/rod) will be administered to all study participants<br>* Other names: Implanon;Drug: rilpivirine<br>* Oral rilpvirine 25mg<br>* Other names: Edurant;|
| Other: Darunavir arm<br>All subjects will be administered oral DRV/r 600/100mg twice daily together with the rest of their oral antiretroviral combination and an etonogestrel single-rod subdermal implant (68mg/rod). Study participants will have both interventions for a period of one year. | Drug: Etonogestrel 68Mg Implant<br>* Etonogestrel single-rod subdermal implant (68mg/rod) will be administered to all study participants<br>* Other names: Implanon;Drug: darunavir<br>* Oral darunavir+ritonavir 600/100mg<br>* Other names: DRV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of etonogestrel | Comparison of the mean etonogestrel concentrations at month 6 between rilpivirine and darunavir treatment groups versus historical controls. | Six months of combined use. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of rilpivirine and darunavir | Rilpivirine and darunavir mean concentration changes prior to implant placement and then over the duration of the study time period. | 12 months | 
| Number and severity of adverse events | Any signs and symptoms related to hormone exposure, including abnormal vaginal bleeding and local or systemic adverse events observed during the study period in both study groups. | 12 months |