Pharmacokinetic Interactions Between DMPA and LPV/Rit Among HIV-Infected Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01296152
First received: February 14, 2011
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

This study is being done to look at the level of Depo-Provera, an injectable birth control, in the blood to see whether it is affected by the anti-HIV drug Kaletra (lopinavir/ritonavir [LPV/r]). It is not known whether taking Depo-Provera together with Kaletra changes the amount of Kaletra in blood. Therefore, this study will also look at the levels of HIV and Kaletra before and after receiving a shot of Depo-Provera. This study will take a look at the safety of Depo-Provera and Kaletra when they are used together. In addition to what is stated above, this study will also explore any effect of Depo-Provera on the immune system.


Condition Intervention Phase
HIV-1 Infection
Drug: depo-medroxyprogesterone acetate
Drug: Depo-medroxyprogesterone Acetate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Between Depo-Medroxyprogesterone Acetate (DMPA) and Lopinavir/Ritonavir (LPV/r) and of the Effects of DMPA on Cellular Immunity and Regulation in HIV-Infected Women

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Natural log-transformed medroxyprogesterone acetate (MPA) pharmacokinetic parameter area under the concentration-time curve (AUC) obtained from this study and natural log-transformed MPA PK AUC0-12wk from the study control arm in ACTG A5093 [ Time Frame: Day 0 to Week 12 ] [ Designated as safety issue: Yes ]
    This will evaluate the effect of lopinavir/ritonavir (LPV/r) on pharmacokinetic parameter AUC of MPA. This evaluation will be performed using two-sample nonparametric Wilcoxon test by comparing the PK AUCs of MPA from this current study with the PK AUCs of MPA from individual subjects enrolled into the study control arm (MPA administered alone, N=14) in ACTG A5093.

  • Determine the effect of MPA on the PK of lopinavir (LPV) among HIV-infected subjects using the AUC for LPV at baseline (day 0) before MPA administration and at week 4 [ Time Frame: Day 0 to Week 4 ] [ Designated as safety issue: Yes ]
    This will evaluate the effect of DMPA on LPV PK parameter AUC. This evaluation will be performed using the paired-sample nonparametric Wilcoxon test by comparing PK AUCs of LPV obtained on study Day 0 (before DMPA is administered) with PK AUCs of LPV on study Week 4 (4 weeks after DMPA is administered).


Secondary Outcome Measures:
  • Progesterone levels obtained at study weeks 0, 2, 4, 6, 8, 10, and 12 from both this current study and the study control arm in ACTG A5093 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    This evaluates the suppression of ovulation due to the potential PK interaction between DMPA and LPV/r.

  • Natural log-transformed MPA PK parameters Cmin, Cmax. Tmax, T1/2, and Cl/F determined based on MPA levels obtained at study weeks 0, 2, 4, 6, 8, 10, and 12 from this current study and those from the study control arm in ACTG A5093 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    This evaluates the effect of LPV/r on the secondary MPA PK parameters.

  • Natural log-transformed LPV PK parameters Cmin, Cmax, Tmax, T1/2, and Cl/F obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    This evaluates the effect of MPA on the secondary LPV PK parameters.

  • Natural log-transformed RTV PK parameters AUC0-12h, Cmin, Cmax, Tmax, and Cl/F obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    This evaluates the effect of MPA on the PK parameters of RTV.

  • Laboratory toxicities and signs and symptoms with toxicity grades recorded while on study. HIV-1 RNA copies at study entry and study week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    This evaluates toxicity and safety of concomitant medication of DMPA and LPV/r and also evaluates the short-term virologic suppression.

  • CMI to HIV and two common opportunistic agents C. albicans (candida) and varicella-zoster virus (VZV) measured at baseline before DMPA and after DMPA at week 4 and at week 12 using flow cytometry [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    This evaluates the effect of MPA on cell-mediated immunity to HIV and the common opportunistic agents.

  • Tregs at baseline, week 4, and week 12 using flow cytometry in freshly thawed and in antigen-stimulated PBMCs measured at baseline before DMPA and after DMPA at week 4 and week 12 using flow cytometry [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    This evaluates the effect of MPA on Tregs.


Enrollment: 25
Study Start Date: May 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Depo-medroxyprogesterone acetate (DMPA)
At study entry/ Day 0, subjects will receive depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Drug: depo-medroxyprogesterone acetate
At study entry/ Day 0, participants will receive Depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Other Name: DMPA
Drug: Depo-medroxyprogesterone Acetate
Other Names:
  • DMPA
  • Depo-Provera

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection
  • Documentation of plasma HIV-1 RNA </= 400 copies/mL within 30 days prior to study entry.
  • Last menstrual period </= 35 days prior to study entry.
  • If last menstrual period >35 days prior to study entry, serum follicle-stimulating hormone (FSH) must be </= 40 MIU/mL
  • Stable ARV regimen consisting of BID LPV/r plus 2 or more NRTIs for at least 30 days if postpartum or for at least the previous 14 days if on a previously stable antiretroviral regimen without modifications prior to study entry
  • CD4+ cell count ≥200 cells/mm3 within 30 days prior to study entry
  • Certain laboratory values within 30 days prior to study entry
  • Premenopausal females with normal ovarian function
  • Negative serum or urine-HCG pregnancy test within 72 hours prior to study entry
  • All subjects 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.Subjects 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.
  • Ability and willingness to give written informed consent
  • Documentation of Pap smear within one year prior to study entry.
  • Documentation of hepatitis B (surface antigen) and hepatitis B (core antibody) and hepatitis C (antibody) status prior to study entry.
  • Documentation of VZV status by history of varicella or herpes zoster, or history of varicella or herpes zoster vaccination or documentation of anti-VZV antibodies.
  • Willingness to abstain from alcohol 24 hours prior to and during the 10-hour PK specimen draws.
  • Willingness to abstain from any grapefruit product or supplement for 24 hours prior to entry and for the duration of the study.

Exclusion Criteria:

  • Received DMPA within 180 days prior to study entry.
  • Received other hormonal therapies within the 30 days prior to study entry.
  • Concurrent dual nucleoside therapy of ZDV and d4T within 30 days prior to study entry.
  • Use of any prohibited medications within 30 days prior to study entry. A list of prohibited medications is on the study's protocol specific web page.
  • Breastfeeding.
  • Less than 30 days postpartum at study entry.
  • Bilateral oophorectomy.
  • Hypersensitivity to DMPA, MPA, or any of the other ingredients in DMPA.
  • More than a 50% change in tobacco smoking within the 30 days prior to study entry or plans to significantly change tobacco use during the study.
  • Invasive cancer of the reproductive tract; known or suspected malignancy of the breast, or known increased risk for breast cancer; undiagnosed vaginal bleeding; liver tumors; or serious ocular disorders at any time prior to study entry.
  • Uncontrolled hypothyroidism or hyperthyroidism within 30 days of study entry.
  • Acute infections or other opportunistic diseases requiring medication within 14 days prior to study entry.
  • Receipt of any immunizations within 2 weeks prior to enrollment.
  • Use of any immunosuppressant medication including systemic corticosteroids within 30 days prior to study entry.
  • Chronic immunosuppressive conditions other than HIV.
  • Initiated, discontinued, or changed doses of drugs that are CYP 3A4 substrates within 30 days of study entry.
  • History of deep venous thrombosis or pulmonary emboli.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296152

Locations
United States, Alabama
Univ. of Alabama Birmingham NICHD CRS (5096)
Birmingham, Alabama, United States, 35233
United States, California
University of Southern California LA (5048)
Los Angeles, California, United States, 90033
University of California, San Francisco (5091)
San Francisco, California, United States, 94143
United States, District of Columbia
Washington Hospital Center NICHD CRS (5023)
Washington, District of Columbia, United States, 20010
United States, Florida
South Florida Childrens Diagnostic & Treatment Cen (5055)
Ft. Lauderdale, Florida, United States, 33316
United States, Illinois
Rush University Cook County Hospital Chicago NICHD CRS (5083)
Chicago, Illinois, United States, 60612
Northwestern University CRS (2701)
Chicago, Illinois, United States, 60611
Chicago Children's CRS (4001)
Chicago, Illinois, United States, 60612
United States, Massachusetts
WNE Maternal Pediatric Adolescent AIDS CRS (7301)
Worcester, Massachusetts, United States, 01605
United States, New Jersey
NJ Med School CRS (2802)
Newark, New Jersey, United States, 07103
United States, New York
Univ. of Rochester ACTG CRS (1101)
Rochester, New York, United States, 14642
AIDS Care CRS (1108)
Rochester, New York, United States, 14642
SUNY Stony Brook NICHD CRS (5040)
Stony Brook, New York, United States, 11794
United States, North Carolina
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27516
Duke Univ. Med. Ctr. Adult CRS (1601)
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267-0405
Puerto Rico
San Juan Hospital PR NICHD CRS (5031)
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Susan E Cohn, M.D., M.P.H. Northwestern University CRS
Study Chair: Amneris E Luque, M.D. University of Rochester ACTG CRS
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01296152     History of Changes
Other Study ID Numbers: ACTG A5283, 1U01AI068636
Study First Received: February 14, 2011
Last Updated: June 5, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Medroxyprogesterone Acetate
Medroxyprogesterone
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral

ClinicalTrials.gov processed this record on September 29, 2014