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Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women

Primary Purpose

HIV/AIDS, Contraception

Status

Completed

Phase

Phase 2

Locations

Uganda

Study Type

Interventional

Intervention

etonogestrel implant

About this trial

This is an interventional treatment trial for HIV/AIDS focused on measuring etonogestrel, efavirenz, antiretroviral therapy, HIV

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept 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.

Sites / Locations

Infectious Disease Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard Dose Etonogestrel Implant

Increased Dose Etonogestrel Implant

Arm Description

Single 68 mg etonogestrel implant

Two 68 mg (136 mg total) etonogestrel implants

Outcomes

Primary Outcome Measures

Ovulation

Ovulation evaluated by endogenous progesterone concentrations of >3ng/mL

Secondary Outcome Measures

Cervical mucus quality

World Health Organization Cervical Mucus Scores

Etonogestrel pharmacokinetics

Etonogestrel serum concentrations

Adverse events

Safety

Full Information

NCT ID

NCT03282799

First Posted

September 12, 2017

Last Updated

March 10, 2023

Sponsor

Catherine Anne Chappell

Collaborators

Infectious Disease Institute, Kampala, Uganda, University of Nebraska

1. Study Identification

Unique Protocol Identification Number

NCT03282799

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

February 19, 2019 (Actual)

Primary Completion Date

December 22, 2020 (Actual)

Study Completion Date

October 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Catherine Anne Chappell

Collaborators

Infectious Disease Institute, Kampala, Uganda, University of Nebraska

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV/AIDS, Contraception

Keywords

etonogestrel, efavirenz, antiretroviral therapy, HIV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard Dose Etonogestrel Implant

Arm Type

Active Comparator

Arm Description

Single 68 mg etonogestrel implant

Arm Title

Increased Dose Etonogestrel Implant

Arm Type

Experimental

Arm Description

Two 68 mg (136 mg total) etonogestrel implants

Intervention Type

Drug

Intervention Name(s)

etonogestrel implant

Other Intervention Name(s)

Nexplanon, Implanon

Intervention Description

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

Primary Outcome Measure Information:

Title

Ovulation

Description

Ovulation evaluated by endogenous progesterone concentrations of >3ng/mL

Time Frame

weekly at months 3, 6, and 12

Secondary Outcome Measure Information:

Title

Cervical mucus quality

Description

World Health Organization Cervical Mucus Scores

Time Frame

weekly at months 3, 6, and 12

Title

Etonogestrel pharmacokinetics

Description

Etonogestrel serum concentrations

Time Frame

Week 1, 4, 12, 24, 36, and 48

Title

Adverse events

Description

Safety

Time Frame

up to months 12

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

Infectious Disease Institute

City

Kampala

Country

Uganda

12. IPD Sharing Statement

Plan to Share IPD

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Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women

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