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

NCT ID: NCT01296152

Last Updated: 2015-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2012-10-31

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.

Detailed Description

The primary study objective was addressed by calculating the Area Under the Concentration-Time Curve (AUC) from week 0 (prior to DMPA injection) to week 12 (twelve weeks after DMPA injection) in our study participants.

DMPA was supplied and administered as part of the protocol, however Kaletra was not. It was required that participants already be on a Kaletra based regimen prior to entering the study, as described in the eligibility criteria.

Arm A of AIDS Clinical Trial Group (ACTG) A5093, which consisted of 14 participants who were administered DMPA without Kaletra, was used as reference data.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Depo-medroxyprogesterone acetate (DMPA)

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

Group Type: EXPERIMENTAL

depo-medroxyprogesterone acetate

Intervention Type: DRUG

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

Interventions

depo-medroxyprogesterone acetate

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

Intervention Type: DRUG

Other Intervention Names

DMPA; Depo-Provera

Eligibility 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 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.
• 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 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)
• glucocorticoids
• Hypericum perforatum (St. John's wort)
• itraconazole (Sporanox)
• ketoconazole (Nizoral)
• lovastatin (Mevacor)
• midazolam (Versed)
• nefazadone (Serzone)
• phenobarbital (Luminal)
• phenytoin (Dilantin)
• pimozide (Orap)
• pioglitazone (Actos)
• propafenone (Rythmol)
• propofol (Diprivan)
• quinidine (Quinidex)
• rifabutin (Mycobutin)
• rifampin (Rifadin, Rifamate, Rifater, Rimactane)
• rosiglitazone (Avandia)
• simvastatin (Zocor)
• tacrolimus (Prograf)
• terfenadine
• ticlopidine (Ticlid), and
• triazolam (Halcion)
• 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 cytochrome P450 3A4 (CYP3A4) substrates within 30 days of study entry.
• History of deep venous thrombosis or pulmonary emboli.

• Minimum Eligible Age: 13 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan E Cohn, M.D., M.P.H.

Role: STUDY_CHAIR

Northwestern University CRS

Amneris E Luque, M.D.

Role: STUDY_CHAIR

University of Rochester ACTG CRS

Locations

University of Southern California LA (5048)

Los Angeles, California, United States

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

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

Washington Hospital Center NICHD CRS (5023)

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

South Florida Childrens Diagnostic & Treatment Cen (5055)

Fort Lauderdale, Florida, United States

Northwestern University CRS (2701)

Chicago, Illinois, United States

Rush University Cook County Hospital Chicago NICHD CRS (5083)

Chicago, Illinois, United States

Tulane University New Orleans NICHD CRS (5095)

New Orleans, Louisiana, United States

Univ. of Rochester ACTG CRS (1101)

Rochester, New York, United States

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, United States

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

University of Washington AIDS CRS (1401)

Seattle, Washington, United States

San Juan Hospital PR NICHD CRS (5031)

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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)

Reference Type: 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.

Reference Type: RESULT

PMID: 25624326 (View on PubMed)

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5283

Identifier Type: -

Identifier Source: org_study_id