PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02412436
• Date of registration: 17/03/2015
• Prospective Registration: Yes
• Primary sponsor: AIDS Clinical Trials Group
• Public title: PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB PRIDE-HT
• Scientific title: An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Among Depot Medroxyprogesterone Acetate (DMPA), Rifampicin (RIF), and Efavirenz (EFV) in Women Co-infected With Human Immunodeficiency Virus (HIV) and Tuberculosis (TB)
• Date of first enrolment: November 3, 2015
• Target sample size: 62
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02412436
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Botswana, Kenya, South Africa, Zimbabwe

Contacts

• Name: Rosie Mngqibisa, MBChB, MPH
• Affiliation: Durban Adult HIV CRS

• Name: Susan E. Cohn, MD, MPH
• Affiliation: Northwestern University

• Name: Jennifer Robinson, MD, MPH
• Affiliation: Johns Hopkins University

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 46 Years
Gender: Female

Health Condition(s) or Problem(s) studied

HIV-1 Infection

Tuberculosis

Intervention(s)

Drug: Depot medroxyprogesterone acetate

Primary Outcome(s)

Percent of Participants With Progesterone Levels Above 1 ng/mL at Week 12 [Time Frame: Week 12]

Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Week 12 [Time Frame: Week 12]

Secondary Outcome(s)

Time at Which Participant-specific Estimated Elimination Slopes for DMPA Level Cross the Threshold of 0.1 ng/mL [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

Percent of Participants Who Experienced a Grade 3 or Higher Sign/Symptom or Laboratory Abnormality [Time Frame: Weeks 2, 4, 6, 8, 10, and 12]

DMPA Cmax [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

Cumulative Percentage of Participants With DMPA < 0.1 ng/mL [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

DMPA AUC [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

DMPA Cmin [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

DMPA CL/F [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Weeks 2, 4, 6, 8, and 10 [Time Frame: Weeks 2, 4, 6, 8, and 10]

DMPA Half-life [Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12]

Secondary ID(s)

UM1AI068636

ACTG A5338

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Allergy and Infectious Diseases (NIAID)

Results

• Results available: Yes
• Date Posted: 25/09/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02412436