Pharmacokinetic Study to Evaluate Double-Dose Levonorgestrel Emergency Contraception in Combination With Efavirenz-Based Antiretroviral Therapy or Rifampicin-Containing Anti-Tuberculosis Therapy

• Status: Completed
• Trial end date: 2020-11-30
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this pharmacokinetic (PK) study is to evaluate if a double dose (3 mg) of levonorgestrel (LNG) emergency contraception (EC) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of double-dose (3.0 mg) LNG EC versus standard-dose (1.5 mg) will also be compared.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Clinical Trials Group; National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Anti-Retroviral Agents; Antitubercular Agents; Efavirenz; Levonorgestrel; Rifampin

Criteria

Inclusion Criteria:

• Postmenarcheal female.

• Note: Participant report and clinician's opinion are acceptable.

• The following laboratory values obtained within 30 days prior to study entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance (EQA) programs.

• Absolute neutrophil count (ANC) greater than or equal to 500 cells/mm^3

• Platelet count greater than or equal to 50,000 platelets/mm^3

• Hemoglobin greater than or equal to 8.0 g/dL

• Aspartate transaminase (AST) less than 5 x upper limit of normal (ULN)

• Alanine aminotransferase (ALT) less than 5 x ULN

• Creatinine less than or equal to 1.5 x ULN

• Total bilirubin less than or equal to 2.0 x ULN

• Negative serum or urine pregnancy test within 30 days prior to study entry and within 48 hours prior to entry (if screening occurs more than 48 hours prior to entry) by any US clinic or US laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or non-US clinic that operates in accordance with GCLP and participates in appropriate EQA programs. The serum or urine pregnancy test must have a sensitivity of at least 25 mIU/mL.

• Has not had sex that could lead to pregnancy without contraception within 14 days prior to study entry as defined in the criteria below, according to participant self-report.

• Contraception requirements

• All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) for the duration of the study. Women of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while in the study. Acceptable forms of contraceptives include:

• Male condom with or without a spermicidal agent

• Diaphragm or cervical cap with spermicide

• Non-hormonal intrauterine device (IUD)

• Bilateral tubal ligation

• Male partner vasectomy

• Women and girls 16 years of age and older.

• Ability and willingness of participant or legal guardian/representative to provide informed consent.

• Body mass index (BMI) (kg/m^2) available at entry. See the study protocol for BMI calculation instructions.

• Note: A maximum of 5 participants with BMI greater than or equal to 30 kg/m^2 will be allowed in each arm B-D and a maximum of 3 participants in Arm A.

• For women living with HIV: HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

• Note: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all investigational new drug (IND) studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies.

• World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.

• For women living with HIV: Receiving a stable qualifying concomitant ART regimen containing either once-daily DTG 50 mg or EFV 600 mg with no changes in the components of their ART for at least 30 days prior to study entry.

• For women who are being treated for TB: HIV-negative at screening, documented within the prior 6 months by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.

• Note: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies.

• WHO and CDC guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.

• For women who are HIV-negative and being treated for TB: Receiving RIF and INH on a once daily dosing (7 days per week) schedule at study entry, after completion of the intensive phase of TB treatment.

• Note: Inclusion of ethambutol as part of continuation phase of TB therapy is allowed.

• Ability and willingness of participant to be contacted remotely for study visits.

Exclusion Criteria

• Known allergy/sensitivity or any hypersensitivity to LNG or components of the formulation.

• Bilateral oophorectomy, hysterectomy, or postmenopausal

• Note: Postmenopausal is defined as amenorrhea for at least 12 consecutive months prior to study entry (in the absence of medications known to induce amenorrhea), and have a documented follicle stimulated hormone-release factor (FSH) measurement greater than 40 mIU/mL or a result in the testing laboratory's menopausal range. If an FSH level is not available, 24 consecutive months of amenorrhea prior to study entry (in the absence of medications known to induce amenorrhea).

• Note: Clinical assessment and clinician's opinion are acceptable.

• Currently pregnant, within 6 weeks of delivery, or currently breastfeeding an infant under 6 months of age.

• Note: For recent pregnancy resolution during the first or second trimester, the participant is only eligible when the pregnancy test result is negative.

• Receipt of LNG within 30 days prior to study entry.

• Receipt of depo-medroxyprogesterone for 90 days prior to study entry, or norethisterone enanthate (NET-EN) within 60 days prior to study entry, or other hormonal contraceptives within 30 days prior to study entry.

• Use of any drugs other than RIF and EFV known to: 1) induce CYP3A4 system within 30 days prior to study entry, and 2) inhibit the CYP3A4 system within 7 days prior to study entry. See the study protocol for prohibited and precautionary medications.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• Acute or serious illness requiring systemic treatment and/or hospitalization within 14 days prior to study entry.

• Other medical, psychiatric, or psychological condition that, in the opinion of the site investigator, would interfere with completion of study procedures and or adherence to study drug.

• For women living with HIV: Currently receiving medications for TB infection.

• For women living with HIV: Has missed one or more of the prescribed doses of HIV medications within 3 days prior to study entry.

• Note: The entry visit may be rescheduled within the screening period once the participant has taken all prescribed doses within 3 days prior to study entry.

• For women who are HIV-negative and being treated for TB: Has missed one or more of the prescribed doses of TB medication within 3 days prior to study entry.

• Note: The entry visit may be rescheduled within the screening period once the participant has taken all prescribed doses within 3 days prior to study entry.