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

Completed · Phase 2

Conditions studied: HIV Infections, Tuberculosis

In brief

The purpose of this pharmacokinetic (PK) study was to evaluate if a double dose (3 mg) of levonorgestrel (LNG) 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 versus standard-dose (1.5 mg) was also compared.

Key facts

Study ID

NCT03819114

Run by

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

People needed

122

Starts

2019-05-06

Expected to finish

2020-11-30

Last updated by the study team

2021-12-27

Who can join

Age: 16 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Postmenarcheal female.
• Note: Participant report and clinician's opinion were acceptable.
• The following laboratory values obtained within 30 days prior to study entry by any US laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any ACTG network-approved non-US laboratory that operated in accordance with Good Clinical Laboratory Practices (GCLP) and participated 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 occurred more than 48 hours prior to entry) by any US clinic or US laboratory that had a CLIA certification or its equivalent, or used a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or non-US clinic that operated in accordance with GCLP and participated in appropriate EQA programs. The serum or urine pregnancy test must have had a sensitivity of at least 25 mIU/mL.
• Had 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 agreed 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 were participating in sexual activity that could lead to pregnancy, agreed to use at least one reliable method of contraception while in the study. Acceptable forms of contraceptives included:
• 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
• Ability and willingness of participant or legal guardian/representative to have provided 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 were allowed in each arm B-D and a maximum of 3 participants in Arm A.
• For participants 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" referred to a US Food and Drug Administration (FDA)-approved kit, which was required for all investigational new drug (IND) studies, or for sites located in countries other than the United States, a kit that had been certified or licensed by an oversight body within that country and validated internally. Non-US sites were encouraged to use US FDA-approved methods for IND studies.
• World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandated that confirmation of the initial test result must have used a test that was different from the one used for the initial assessment. A reactive initial rapid test was confirmed by either another type of rapid assay or an E/CIA that was 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.

You may not qualify if…

• Known allergy/sensitivity or any hypersensitivity to LNG or components of the formulation.
• Bilateral oophorectomy, hysterectomy, or postmenopausal
• Note: Postmenopausal was defined as amenorrhea for at least 12 consecutive months prior to study entry (in the absence of medications known to induce amenorrhea), and had 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 was 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 were acceptable.
• Was currently pregnant, was within 6 weeks of delivery, or was currently breastfeeding an infant under 6 months of age.
• Note: For recent pregnancy resolution during the first or second trimester, the participant was only eligible when the pregnancy test result was 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.
• Used 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 have interfered with adherence to study requirements.
• Acute or serious illness that required 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 have interfered with completion of study procedures and or adherence to study drug.
• For participants with HIV: Was currently receiving medications for TB infection.
• For participants with HIV: Had missed one or more of the prescribed doses of HIV medications within 3 days prior to study entry.
• Note: The entry visit could have been rescheduled within the screening period once the participant had taken all prescribed doses within 3 days prior to study entry.
• For participants who were not living with HIV and were being treated for TB: Had missed one or more of the prescribed doses of TB medication within 3 days prior to study entry.
• Note: The entry visit could have been rescheduled within the screening period once the participant had taken all prescribed doses within 3 days prior to study entry.

Where it is running

• 2701 Northwestern University CRS — Chicago, Illinois, United States
• Rush Univ. Med. Ctr. ACTG CRS (2702) — Chicago, Illinois, United States
• Weill Cornell Upton CRS (7803) — New York, New York, United States
• Unc Aids Crs (3201) — Chapel Hill, North Carolina, United States
• Hosp. of the Univ. of Pennsylvania CRS (6201) — Philadelphia, Pennsylvania, United States
• Pitt CRS (1001) — Pittsburgh, Pennsylvania, United States
• Trinity Health and Wellness Center CRS (31443) — Dallas, Texas, United States
• Gaborone CRS (12701) — Gaborone, Botswana
• 12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS — Rio de Janeiro, Brazil
• Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (12501) — Kericho, Kenya
• Blantyre CRS (30301) — Blantyre, Malawi
• Malawi CRS (12001) — Lilongwe, Malawi
• University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101) — Johannesburg, Gauteng, South Africa
• Family Clinical Research Unit (FAM-CUR) CRS (8950) — Cape Town, West Cape, South Africa
• Durban Adult HIV CRS (11201) — Durban, South Africa
• Soweto ACTG CRS (12301) — Johannesburg, South Africa
• 31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS — Bangkok, Patumwan, Thailand
• 31784 Chiang Mai University HIV Treatment CRS — Chiang Mai, Thailand

Full record on ClinicalTrials.gov

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