Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women

Sponsor

Catherine Chappell (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03282799

Collaborator

Infectious Disease Institute, Kampala, Uganda (Other), University of Nebraska (Other)

Enrollment

Location

Arms

46.4

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV/AIDS Contraception	Drug: etonogestrel implant	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan

Actual Study Start Date :

Feb 19, 2019

Actual Primary Completion Date :

Dec 22, 2020

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard Dose Etonogestrel Implant Single 68 mg etonogestrel implant	Drug: etonogestrel implant The etonogestrel implant is an contraceptive implant that is placed into the upper arm. Other Names: Nexplanon Implanon
Experimental: Increased Dose Etonogestrel Implant Two 68 mg (136 mg total) etonogestrel implants	Drug: etonogestrel implant The etonogestrel implant is an contraceptive implant that is placed into the upper arm. Other Names: Nexplanon Implanon

Arm

Intervention/Treatment

Active Comparator: Standard Dose Etonogestrel Implant

Single 68 mg etonogestrel implant

Drug: etonogestrel implant

The etonogestrel implant is an contraceptive implant that is placed into the upper arm.

Other Names:

Nexplanon

Implanon

Experimental: Increased Dose Etonogestrel Implant

Two 68 mg (136 mg total) etonogestrel implants

Drug: etonogestrel implant

The etonogestrel implant is an contraceptive implant that is placed into the upper arm.

Other Names:

Nexplanon

Implanon

Outcome Measures

Primary Outcome Measures

Ovulation [weekly at months 3, 6, and 12]
Ovulation evaluated by endogenous progesterone concentrations of >3ng/mL

Secondary Outcome Measures

Cervical mucus quality [weekly at months 3, 6, and 12]
World Health Organization Cervical Mucus Scores
Etonogestrel pharmacokinetics [Week 1, 4, 12, 24, 36, and 48]
Etonogestrel serum concentrations
Adverse events [up to months 12]
Safety

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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 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.

Exclusion Criteria:

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 labeling15.
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.