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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

February 14, 2011
June 5, 2014
May 2011
October 2012   (final data collection date for primary outcome measure)
  • 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).
Same as current
Complete list of historical versions of study NCT01296152 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Pharmacokinetic Interactions Between DMPA and LPV/Rit Among HIV-Infected Women
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

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-1 Infection
  • 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
Experimental: Depo-medroxyprogesterone acetate (DMPA)
At study entry/ Day 0, subjects will receive depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Interventions:
  • Drug: depo-medroxyprogesterone acetate
  • Drug: Depo-medroxyprogesterone Acetate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
October 2012
October 2012   (final data collection date for primary outcome measure)

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.
Female
13 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01296152
ACTG A5283, 1U01AI068636
Yes
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
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
AIDS Clinical Trials Group
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP