NCT01296152 - Pharmacokinetic Interactions Between DMPA and LPV/r Among HIV-Infected Women | Crick

Eligibility

Sex: FEMALEMin age: 13 Years

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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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Day 0 and Week 4

Secondary Outcomes

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

This evaluates the suppression of ovulation due to the potential PK interaction between DMPA and LPV/r. The LLQ of progesterone is 0.5ng/mL. The threshold for suppression of ovulation is 5ng/mL.