PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB
Condition: HIV-1 Infection; Tuberculosis
MeSH terms: Tuberculosis
Intervention: Depot medroxyprogesterone acetate
Intervention description: Depot medroxyprogesterone acetate intramuscular injection
Intervention MeSH terms: Medroxyprogesterone Acetate; Medroxyprogesterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: Female
Minimum age: 18 Years
Maximum age: 46 Years
Healthy volunteers: No

Summary:

      This study was done to evaluate the effect of HIV and TB treatment on a commonly used birth
      control method. It enrolled women who were infected with HIV and TB and were taking efavirenz
      (EFV; Sustiva®; an anti-HIV medication), rifampicin (RIF; an anti-TB medication), and
      isoniazid (INH; an anti-TB medication). The purpose of this study was to find out the best
      frequency to give depot medroxyprogesterone acetate (DMPA; a hormonal birth control method
      that is given as a shot every 3 months) in these women. This study also tried to find out if
      a 150 mg injection of DMPA was effective in preventing ovulation, the process by which the
      ovaries (the ovaries are part of the female reproductive system) release an egg for
      fertilization, for 12 weeks in women who are taking EFV and RIF. Another purpose of this
      study was to find out if it is safe to take RIF, EFV and DMPA at the same time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection.

          -  Current tuberculosis infection, confirmed or probable diagnosis.

          -  Currently stable on EFV-based cART for at least 28 days with no intention to change
             the regimen during the 12-week study period.

          -  Currently receiving RIF and Isoniazid (INH)-based TB therapy on at least 5 days per
             week schedule after completion of the intensive phase of TB treatment (minimum of 8
             weeks of TB treatment) and expected to be on TB treatment for a minimum of 12 weeks
             after enrollment. [Does not exclude the use of ethambutol on study.]

          -  Premenopausal female with presumed normal ovarian function based on normal menstrual
             history and absence of previous ovarian dysfunction diagnosis.

          -  Last menstrual period (LMP) ≤35 days prior to study entry.

          -  Negative serum or urine-HCG pregnancy test within 30 days prior to study entry and
             negative pregnancy test at entry at any network-approved laboratory that operates in
             accordance with Good Clinical Practices and participates in appropriate external
             quality assurance programs.

          -  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 an additional reliable method of contraception
             while in the study. Acceptable forms of contraceptives include:

               -  Condoms (male or female) with or without a spermicidal agent

               -  Diaphragm or cervical cap with spermicide

               -  Non-hormonal IUD

               -  Bilateral tubal ligation

               -  Male partner vasectomy

          -  Laboratory values within 30 days prior to study entry:

               -  Absolute neutrophil count ≥500 cells/mm^3

               -  Platelet count ≥50,000 platelets/mm^3

               -  Hemoglobin ≥8.0 g/dL

               -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) <5 x upper limit
                  of normal (ULN)

               -  Creatinine ≤1.5 x ULN

               -  Total bilirubin ≤2.0 x ULN

          -  Ability and willingness to provide written informed consent.

        Exclusion Criteria:

          -  Receipt of DMPA or any other injectable contraceptive within 180 days prior to study
             entry.

          -  Receipt of 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 and to 2) inhibit the CYP3A4 system with one week prior to study entry. [Because
             ethambutol does not induce or inhibit the CYP3A4 system, its use is consistent with
             the language in the protocol.]

          -  ≤40 kg in weight.

          -  Bilateral oophorectomy.

          -  Less than 30 days postpartum at study entry.

          -  Hypersensitivity to DMPA, medroxyprogesterone acetate (MPA), or any of the other
             ingredients in DMPA.

          -  Any previous breast cancer diagnosis.

          -  Serious illness requiring systemic treatment and/or hospitalization within 21 days
             prior to study entry.

          -  Karnofsky performance score <70 within 14 days prior to study entry.

          -  Use of any immunosuppressant medication including systemic corticosteroids within 30
             days prior to study entry.

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements.

          -  History of deep venous thrombosis or pulmonary emboli.