PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB

• Status: Completed
• Trial end date: 2017-06-15
• Target enrollment: 0
• Participant gender: Female

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.

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

Details

• Lead Sponsor: AIDS Clinical Trials Group
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Medroxyprogesterone; Medroxyprogesterone Acetate; Rifampin

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.