PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB

NCT02412436 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A5338UM1AI068636
• Study Type: interventional
• Target: 62
• Locations: 4 countries
• Sites: 5

Brief 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.

Conditions

HIV-1 Infection; Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Week 12

  The percent of participants with plasma DMPA concentrations below 0.1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Suppression of ovulation generally occurs as long as the DMPA level is =\> 0.1 ng/mL.

  Week 12

• Percent of Participants With Progesterone Levels Above 1 ng/mL at Week 12

  The percent of participants with plasma progesterone levels above 1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Ovulation generally occurs when the progesterone level is \> 5 ng/mL. If there were participants with plasma progesterone levels \> 1 ng/mL, then the percent of participants with plasma progesterone levels \> 5 ng/mL would have been calculated by study week.

  Week 12

Secondary Outcomes (9)

• Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Weeks 2, 4, 6, 8, and 10

  Weeks 2, 4, 6, 8, and 10

• Cumulative Percentage of Participants With DMPA < 0.1 ng/mL

  Weeks 0, 2, 4, 6, 8, 10, and 12

• DMPA AUC

  Weeks 0, 2, 4, 6, 8, 10, and 12

• DMPA Cmin

  Weeks 0, 2, 4, 6, 8, 10, and 12

• DMPA Cmax

  Weeks 0, 2, 4, 6, 8, 10, and 12

Study Arms (1)

Arm A: Depot medroxyprogesterone acetate

EXPERIMENTAL

At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).

Drug: Depot medroxyprogesterone acetate

Interventions

Depot medroxyprogesterone acetate DRUG

Depot medroxyprogesterone acetate intramuscular injection

Also known as: DMPA

Arm A: Depot medroxyprogesterone acetate

Eligibility Criteria

• Age: 18 Years - 46 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (5)

Gaborone Prevention/Treatment Trials CRS (12701)

Gaborone, Botswana

Location

Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)

Kisumu, 40100, Kenya

Location

Durban Adult HIV CRS (11201)

Durban, 4013 SF, South Africa

Location

Univ. of Witwatersrand CRS (11101)

Johannesburg, South Africa

Location

UZ-Parirenyatwa CRS (30313)

Harare, Zimbabwe

Location

Related Publications (2)

• Haas DW, Mngqibisa R, Francis J, McIlleron H, Robinson JA, Kendall MA, Baker P, Mawlana S, Badal-Faesen S, Angira F, Omoz-Oarhe A, Samaneka WP, Denti P, Cohn SE; AIDS Clinical Trials Group A5338 Study Team. Pharmacogenetics of interaction between depot medroxyprogesterone acetate and efavirenz, rifampicin, and isoniazid during treatment of HIV and tuberculosis. Pharmacogenet Genomics. 2022 Jan 1;32(1):24-30. doi: 10.1097/FPC.0000000000000448.

  PMID: 34369424 DERIVED

• Mngqibisa R, Kendall MA, Dooley K, Wu XS, Firnhaber C, Mcilleron H, Robinson J, Cramer Y, Rosenkranz SL, Roa J, Coughlin K, Mawlana S, Badal-Faesen S, Schnabel D, Omoz-Oarhe A, Samaneka W, Godfrey C, Cohn SE; A5338 Study Team. Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency. Clin Infect Dis. 2020 Jul 27;71(3):517-524. doi: 10.1093/cid/ciz863.

  PMID: 31504342 DERIVED

Related Links

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004; Clarification, August 2009
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

Tuberculosis

Interventions

N,N-dimethyl-4-anisidine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Rosie Mngqibisa, MBChB, MPH

  Durban Adult HIV CRS

  STUDY CHAIR

• Susan E. Cohn, MD, MPH

  Northwestern University

  STUDY CHAIR

• Jennifer Robinson, MD, MPH

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: April 9, 2015
• Study Start: November 3, 2015
• Primary Completion: June 15, 2017
• Study Completion: June 15, 2017
• Last Updated: July 1, 2019
• Results First Posted: September 25, 2018

Record last verified: 2019-06

Locations

ZI (1); BO (1); KE (1); ZA (2)