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Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women

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ClinicalTrials.gov Identifier: NCT03282799
Recruitment Status : Not yet recruiting
First Posted : September 14, 2017
Last Update Posted : June 1, 2018
Sponsor:
Collaborators:
Infectious Disease Institute, Kampala, Uganda
University of Nebraska
Information provided by (Responsible Party):
Catherine Chappell, University of Pittsburgh

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 Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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




Primary Outcome Measures :
  1. Ovulation [ Time Frame: weekly at months 3, 6, and 12 ]
    Ovulation evaluated by endogenous progesterone concentrations of >3ng/mL


Secondary Outcome Measures :
  1. Cervical mucus quality [ Time Frame: weekly at months 3, 6, and 12 ]
    World Health Organization Cervical Mucus Scores

  2. Etonogestrel pharmacokinetics [ Time Frame: Week 1, 4, 12, 24, 36, and 48 ]
    Etonogestrel serum concentrations

  3. Adverse events [ Time Frame: up to months 12 ]
    Safety



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Women age 18 years to 40 years
  4. Diagnosed with HIV infection
  5. Medically eligible for the ENG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use20
  6. Receiving EFV-based ART for a minimum of 3 months prior to screening
  7. Must agree to have concurrent highly effective non-hormonal contraception with a copper IUD, if not previously medically sterilized.
  8. Participants must report regular menses (bleeding for 4-8 days at 21 to 35 day intervals) for the preceding 2 month
  9. 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:

  1. HIV RNA > 50 copies/mL at screening visit
  2. Serum hemoglobin < 10.0 g/dl
  3. Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
  4. Elevations in serum creatinine above 2.5 times the upper limit of normal
  5. 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.
  6. Currently pregnant or postpartum <30 days at study entry.
  7. Breastfeeding women within 6 months of delivery.
  8. Use of hormonal contraception in the preceding 3 months prior to entry
  9. Participants determined to be ineligible for IUD placement by the WHO Medical Eligibility Criteria for Contraceptive Use46
  10. 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.
  11. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03282799


Contacts
Contact: Catherine A Chappell, MD MSc 412-641-1403 chappellca@upmc.edu
Contact: Dionne Best 412-641-5496 bestdm@mail.magee.edu

Locations
Uganda
Infectious Disease Institute Not yet recruiting
Kampala, Uganda
Contact: Mohammed Lamorde, MRCP PhD    +256414307291    mlamorde@idi.co.ug   
Contact: Shadia Nakalema, MBChB, DTMH    +256414307238    snakalema@idi.co.ug   
Principal Investigator: Catherine A Chappell, MD, MSc         
Principal Investigator: Mohammed Lamorde, MRCP PhD         
Principal Investigator: Kim Scarsi, PharmD, MSc         
Sponsors and Collaborators
Catherine Chappell
Infectious Disease Institute, Kampala, Uganda
University of Nebraska

Responsible Party: Catherine Chappell, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03282799     History of Changes
Other Study ID Numbers: PRO17080453
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: June 1, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Catherine Chappell, University of Pittsburgh:
etonogestrel
efavirenz
antiretroviral therapy
HIV

Additional relevant MeSH terms:
Efavirenz
Etonogestrel
Desogestrel
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists