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HIV-1 InfectionPhase 2NCT01296152

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

A Phase 2 study testing depo-medroxyprogesterone acetate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 14 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 13 years and older, women only
Conditions the study is for
HIV-1 Infection
What is being tested?
depo-medroxyprogesterone acetate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
14 sitesin 2 countries
Study dates
May 2011to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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.

Who cannot join

  • 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)
Show all 50Show fewer
  • 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.

Trial locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

United States13 sites
  • Unc Aids Crs (3201)

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

  • Rush University Cook County Hospital Chicago NICHD CRS (5083)

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 45267-0405

  • Univ. of Cincinnati CRS (2401)

    Cincinnati, Ohio, 45267

  • South Florida Childrens Diagnostic & Treatment Cen (5055)

    Fort Lauderdale, Florida, 33316

  • University of Southern California LA (5048)

    Los Angeles, California, 90033

  • Tulane University New Orleans NICHD CRS (5095)

    New Orleans, Louisiana, 70112

  • Univ. of Rochester ACTG CRS (1101)

    Rochester, New York, 14642

  • University of Washington AIDS CRS (1401)

    Seattle, Washington, 98104

  • SUNY Stony Brook NICHD CRS (5040)

    Stony Brook, New York, 11794

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

    Washington D.C., District of Columbia, 20010

  • Washington Hospital Center NICHD CRS (5023)

    Washington D.C., District of Columbia, 20010

Other trials in United States

Puerto Rico1 site
  • San Juan Hospital PR NICHD CRS (5031)

    San Juan, 00936

Other trials in Puerto Rico

About this study

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

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.

Read the 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
Being tested
depo-medroxyprogesterone acetate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • depo-medroxyprogesterone acetateDrug

    Also called DMPA, Depo-Provera

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

Study groups in NCT01296152
Study groupRoleWhat they receive
Depo-medroxyprogesterone acetate (DMPA)ExperimentalAt study entry/ Day 0, subjects will receive depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Receives: Drug: depo-medroxyprogesterone acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Day 0 and Week 4

Secondary outcomes (22)
  1. 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.

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

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

    This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmin based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.

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

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

    This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.

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

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

    This evaluates the effect of LPV/r on the secondary MPA PK parameter Tmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.

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

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

    This evaluates the effect of LPV/r on the secondary MPA PK parameter CL/F based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.

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

  6. MPA PK Parameter Half-Life (T1/2) Determined Based on MPA Levels.

    This evaluates the effect of LPV/r on the secondary MPA PK parameter T1/2 based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.

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

  7. LPV PK Parameter Cmin.

    This evaluates the effect of MPA on the secondary LPV PK parameter Cmin obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  8. LPV PK Parameter Cmax.

    This evaluates the effect of MPA on the secondary LPV PK parameter Cmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  9. LPV PK Parameter Tmax.

    This evaluates the effect of MPA on the secondary LPV PK parameter Tmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  10. LPV PK Parameter CL/F.

    This evaluates the effect of MPA on the secondary LPV PK parameter CL/F obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  11. LPV PK Parameter T1/2.

    This evaluates the effect of MPA on the secondary LPV PK parameter T1/2 obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  12. Ritonavir (RTV) PK Parameter AUC0-12h.

    This evaluates the effect of MPA on the PK parameter AUC0-12h of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. Blood samples were drawn for RTV 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.

    Measured: Day 0 and Week 4

  13. RTV PK Parameter Cmin.

    This evaluates the effect of MPA on the PK parameter Cmin of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  14. RTV PK Parameter Cmax.

    This evaluates the effect of MPA on the PK parameter Cmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  15. RTV PK Parameter Tmax.

    This evaluates the effect of MPA on the PK parameter Tmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  16. RTV PK Parameter CL/F.

    This evaluates the effect of MPA on the PK parameter CL/F of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  17. RTV PK Parameter T1/2.

    This evaluates the effect of MPA on the PK parameter T1/2 of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.

    Measured: Day 0 and Week 4

  18. Percentage of Participants With Menstrual Irregularities of Grade 1 and Higher Deemed Possibly, Probably or Definitely Related to Study Treatment.

    This evaluates toxicity and safety of concomitant medication of DMPA and LPV/r, focusing specifically on the adverse event (AE) menstrual irregularities with abnormal vaginal bleeding. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the study's co-chairs.

    Measured: From day 0 to week 12

  19. Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL.

    This evaluates the short-term impact of MPA on virologic suppression in participants taking LPV/r who have received a dose of DMPA by measuring percentage of participants with HIV-1 RNA levels <400 copies/mL at day 0 (prior to DMPA injection) and at weeks 2, 4, 8 and 12 (after DMPA injection). An FDA-approved HIV-1 RNA assay with a lower limit of detection of 75 copies/mL or less was required and the same HIV-1 RNA assay was required to be performed for each participant across all study visits. The Roche COBAS AmpliPrep/TaqMan HIV-1 and Abbott RealTime HIV-1 tests were used.

    Measured: Day 0, Weeks 2, 4, 8, and 12

  20. Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay.

    This evaluates the effect of MPA on CMI to HIV and VZV at baseline before DMPA (day 0) and after DMPA (weeks 4 and 12) . Cytokines are interferon-gamma (IFN-gamma) and interleukin 2 (IL-2), and Stimuli are HIV and VZV. Summary of adjusted ELISPOT assay results is in spot forming cells (SFC)/10^6 peripheral blood mononuclear cells (PBMC) by study weeks 0, 4 and 12. The outcome measures of IFN-gamma and IL-2 measured for HIV and VZV are presented here together to provide all results pertaining to the same objective in a single data table.

    Measured: Day 0, Weeks 4 and 12

  21. CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA).

    This evaluates the effect of MPA on CMI to HIV and VZV. This outcome was measured at Baseline Before DMPA (Day 0) and After DMPA (Weeks 4 and 12) using the Lymphocyte Proliferation Assay (LPA). The data table shows a summary of LPA assay results by study week with stimuli HIV and VZV. Proliferation results are reported as a stimulation index (SI) which represents the ratio of the stimulated counts per minute to unstimulated control counts per minute.

    Measured: Day 0, Weeks 4 and 12

  22. Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs.

    This evaluates the effect of MPA on Tregs at baseline (Day 0), week 4 and week 12 using flow cytometry in freshly thawed PBMCs. A summary of CD4+ and cluster of differentiation 8 (CD8+) anchored T-cell subsets by study week, in percent that express the marker of interest, is presented here together to provide all results pertaining to this objective in a single data table.

    Measured: Day 0, Weeks 4 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionOct 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01296152
Sponsor's protocol ID
ACTG A5283
Other IDs
1U01AI068636
Status last verified
Nov 2015
First submitted
14 Feb 2011
Last updated
22 Dec 2015
Data monitoring committee
Yes

Publications

  • 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)

  • 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.

    PubMed 25624326

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing depo-medroxyprogesterone acetate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 14 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 50 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Medroxyprogesterone Acetate (MPA) Pharmacokinetic Parameter (PK) Area Under the Concentration-time Curve (AUC0-12weeks) (time frame: Day 0, Weeks 2, 4, 6, 8, 10 and 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01296152, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2015.

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