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

NCT01296152 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52831U01AI068636
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 14

Brief Summary

This study was 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 also looked at the levels of HIV and Kaletra before and after receiving a shot of Depo-Provera. This study evaluated the safety of Depo-Provera and Kaletra when they are used together. In addition to what is stated above, this study also explored any effect of Depo-Provera on the immune system.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (2)

• Medroxyprogesterone Acetate (MPA) Pharmacokinetic Parameter (PK) Area Under the Concentration-time Curve (AUC0-12weeks)

  This evaluates the effect of lopinavir/ritonavir (LPV/r) on pharmacokinetic parameter AUC of MPA by looking at the MPA AUC from day 0 to week 12. AUC0-12weeks was calculated using single MPA concentrations sampled immediately prior to DMPA administration on day 0, and at 2, 4, 6, 8, 10 and 12 weeks after administration of the single DMPA dose.

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

• AUC0-12hour for LPV at Baseline (Day 0) Before DMPA Administration and at Week 4 (Four Weeks After DMPA Administration)

  This evaluates the effect of DMPA on LPV PK parameter AUC by comparing PK AUCs of LPV from 0 to 12 hours obtained at study Day 0 (before DMPA was administered) with PK AUCs of LPV from 0 to 12 hours at study Week 4 (4 weeks after DMPA was administered). Blood samples were drawn for LPV concentration levels at time zero (before LPV/r dosing) and at 30 minutes and 1, 2, 3, 4, 5, 6, 8 and 10 hours after LPV/r dosing at day 0 and week 4.

  Day 0 and Week 4

Secondary Outcomes (22)

• Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ).

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

• MPA PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on MPA Levels.

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

• MPA PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on MPA Levels.

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

• MPA PK Parameter Time to Cmax (Tmax) Determined Based on MPA Levels.

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

• MPA PK Parameter Clearance (CL/F) Determined Based on MPA Levels.

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

Study Arms (1)

Depo-medroxyprogesterone acetate (DMPA)

EXPERIMENTAL

At study entry/ Day 0, subjects will receive depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.

Drug: depo-medroxyprogesterone acetate

Interventions

depo-medroxyprogesterone acetate DRUG

At study entry/ Day 0, participants will receive Depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.

Also known as: DMPA, Depo-Provera

Depo-medroxyprogesterone acetate (DMPA)

Eligibility Criteria

• Age: 13 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Milli-International units per Milliliter (MIU/mL)
• Stable anti-retroviral (ARV) regimen consisting of BID LPV/r plus 2 or more nucleoside reverse transcriptase inhibitors (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
• Cluster of Differentiation 4 (CD4+) cell count ≥200 cells/mm\^3 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-Human Chorionic Gonadotropin (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 varicella-zoster virus (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 pharmacokinetic (PK) specimen draws.

You may not qualify if:

• 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 zidovudine (ZDV) and stavudine (d4T) within 30 days prior to study entry.
• Use of any prohibited medications within 30 days prior to study entry. Prohibited Medications were:
• amiodarone (Cordarone)
• astemizole (Hismanal)
• bepridil (Vascor)
• carbamazepine (Tegretol)
• cisapride (Propulsid)
• clarithromycin (Biaxin)
• cyclosporine (Sandimmune, Neoral)
• dihydroergotamine (Migranal and others)
• ergotamine (Ergostat, Gotamine, and others)
• erythromycin (E-mycin, erythromycin ethylsuccinate (EES) and others)
• flecainide (Tambocor)

Sponsors & Collaborators

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

Study Sites (14)

University of Southern California LA (5048)

Los Angeles, California, 90033, United States

Location

Children's National Medical Center Washington DC NICHD CRS (5015)

Washington D.C., District of Columbia, 20010, United States

Location

Washington Hospital Center NICHD CRS (5023)

Washington D.C., District of Columbia, 20010, United States

Location

South Florida Childrens Diagnostic & Treatment Cen (5055)

Fort Lauderdale, Florida, 33316, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Rush University Cook County Hospital Chicago NICHD CRS (5083)

Chicago, Illinois, 60612, United States

Location

Tulane University New Orleans NICHD CRS (5095)

New Orleans, Louisiana, 70112, United States

Location

Univ. of Rochester ACTG CRS (1101)

Rochester, New York, 14642, United States

Location

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, 11794, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

San Juan Hospital PR NICHD CRS (5031)

San Juan, 00936, Puerto Rico

Location

Related Publications (2)

• The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)

  BACKGROUND

• Luque AE, Cohn SE, Park JG, Cramer Y, Weinberg A, Livingston E, Klingman KL, Aweeka F, Watts DH. Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study. Antimicrob Agents Chemother. 2015 Apr;59(4):2094-101. doi: 10.1128/AAC.04701-14. Epub 2015 Jan 26.

  PMID: 25624326 RESULT

MeSH Terms

Interventions

Medroxyprogesterone Acetate; N,N-dimethyl-4-anisidine

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

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

• Susan E Cohn, M.D., M.P.H.

  Northwestern University CRS

  STUDY CHAIR

• Amneris E Luque, M.D.

  University of Rochester ACTG CRS

  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: February 14, 2011
• First Posted: February 15, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 22, 2015
• Results First Posted: December 22, 2015

Record last verified: 2015-11

Locations

PR (1); US (13)