HIV InfectionsNCT00016601
Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) Use With Certain Anti-HIV Drugs in HIV-Infected Women
A study testing Indinavir sulfate, Ritonavir and Nelfinavir mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 32 sites in 2 countries.
Trial summary
The purpose of this study is to look at the level of depo-medroxyprogesterone acetate (DMPA or Depo-Provera) in the blood to see if is affected by certain anti-HIV drugs (nelfinavir [NFV], efavirenz [EFV], indinavir [IDV] in combination with ritonavir [RTV], and nevirapine [NVP]). Read more about this study
- Who is it for?
- Ages 13 years and older, women only
- Conditions the study is for
- HIV Infections
- What is being tested?
- Indinavir sulfate, Ritonavir and Nelfinavir mesylate
- How many people
- 76 participants
- Where
- 32 sitesin 2 countries
- Study dates
- Jun 2001to May 2004
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients may be eligible for this study if they:
- Are HIV-positive.
- Have plasma HIV-1 RNA (level of HIV in the blood) below 10,000 copies/ml within 30 days before study entry.
- Had their last menstrual period (LMP) less than 35 days before study entry.
- Have serum follicle-stimulating hormone below 40 MIU/ml if their LMP occurred more than 35 days before study entry.
- Have been on the same anti-HIV drugs for at least 30 days before study entry, if taking anti-HIV drugs. If not taking anti-HIV drugs, patients must have been told about anti-HIV drugs within the 3 months before study entry and have chosen not to take them now or in the future.
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- Intend to continue on their anti-HIV drugs, if taking them, for at least 3 months after study entry.
- Have a CD4 cell count above 200 cells/mm3 if taking anti-HIV drugs, or a CD4 cell count above 350 cells/mm3 if not taking anti-HIV drugs, within 30 days before study entry.
- Have not had menopause (change of life) and have a normal reproductive system.
- Have not had any infections or AIDS-related diseases requiring drugs within 14 days before study entry.
- Are 13 years of age or older.
- Are female.
- Have a negative pregnancy test within 30 days before study entry.
- Agree to avoid becoming pregnant for the entire study. If sexually active, agree to use at least 1 barrier method of birth control (male or female condom with or without spermicide [a cream or gel that kills sperm] or diaphragm or cervical cap with spermicide) while receiving DMPA in this study.
- Have consent of a parent or guardian if under 18 years of age.
- Weigh at least 40 kg (88 lbs) and are within a certain range of their ideal body weight.
Who cannot join
- Patients will not be eligible for this study if they:
- Have taken anti-HIV drugs within 30 days before study entry but have chosen not to take them.
- Are taking only 1 NRTI.
- Are taking anti-HIV drugs other than those listed in the treatment groups, including tenofovir, amprenavir, and lopinavir/ritonavir, or have taken tenofovir, amprenavir, or lopinavir/ritonavir within 30 days before study entry.
- Have taken ZDV and d4T together within 30 days before study entry.
- Are not able to take the anti-HIV drugs properly while on the study, in the opinion of the investigator.
Show all 21Show fewer
- Are allergic to DMPA, MPA, or any of the other ingredients in DMPA.
- Have received DMPA within 180 days before study entry.
- Have received other hormones (Provera, oral contraceptives, hormonal replacement therapy, or anabolic drugs [e.g., nandrolone decanoate, megestrol acetate]) within 30 days before study entry.
- Are taking any of the following: amiodarone, astemizole, bepridil, buspirone, carbamazepine, cimetidine, cisapride, clarithromycin, cyclosporine, dihydroergotamine, diltiazem, ergotamine, erythromycin, flecainide, glucocorticoids, grapefruit juice, St. John's wort, itraconazole, ketoconazole, lovastatin, midazolam, nefazodone, phenobarbital, phenytoin, pimozide, pioglitazone, propafenone, propofol, quinidine, rifabutin, rifampin, rosiglitazone, simvastatin, tacrolimus, terfenadine, ticlopidine, triazolam, or verapamil.
- Have taken any of the following drugs within 30 days before study entry: amiodarone, astemizole, bepridil, buspirone, carbamazepine, cisapride, clarithromycin, cyclosporine, dihydroergotamine, ergotamine, erythromycin, flecainide, glucocorticoids, St. John's wort, itraconazole, ketoconazole, lovastatin, midazolam, nefazodone, phenobarbital, phenytoin, pimozide, pioglitazone, propafenone, propofol, quinidine, rifabutin, rifampin, rosiglitazone, simvastatin, tacrolimus, terfenadine, ticlopidine, or triazolam.
- Have started, stopped, or changed doses, within 30 days before study entry, of certain drugs including: benzodiazepines, except midazolam and triazolam; bupropion; calcium channel blockers, except diltiazem and verapamil; fluconazole; lipid-lowering drugs except pravastatin (i.e., atorvastatin, cerivastatin, and fluvastatin, but not lovastatin and simvastatin); isoniazid; mexiletine; zaleplon; and zolpidem. The patient can, however, remain on stable doses of these drugs during the study.
- Are receiving methadone maintenance treatment for less than 60 days before study entry.
- Are breast-feeding.
- Have had a baby within 30 days before study entry.
- Have had their uterus or both ovaries removed.
- Abuse drugs or alcohol.
- Cannot stop drinking alcohol 1 day before and during the testing at entry and at Week 4.
- Have had a change in smoking habits within 6 weeks before study entry. Patients may have either stopped or started smoking more than 6 weeks before study entry.
- Have cancer of the reproductive system, vaginal bleeding of unknown cause, thyroid problems, liver tumors, or serious eye problems at any time before study entry.
- Are taking investigational drugs without approval of the protocol chair.
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
United States31 sites
Univ of Maryland, Institute of Human Virology
Baltimore, Maryland, 21201
Univ of Alabama at Birmingham
Birmingham, Alabama, 35294
Boston Med Ctr (Pediatric)
Boston, Massachusetts, 02118
Univ of North Carolina
Chapel Hill, North Carolina, 27514
Mt Sinai Hosp Med Ctr / Dept of Pediatrics
Chicago, Illinois, 60608
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, 60612
Chicago Childrens Memorial Hosp (Pediatric)
Chicago, Illinois, 60614-3394
The Univ of Chicago Childrens Hosp
Chicago, Illinois, 60637
Univ of Cincinnati
Cincinnati, Ohio, 452670405
Case Western Reserve Univ
Cleveland, Ohio, 44106-5083
MetroHealth Med Ctr
Cleveland, Ohio, 44109-1998
Children's Hosp of Denver
Denver, Colorado, 802181088
Children's Hosp of Michigan
Detroit, Michigan, 48201
Univ of Texas Galveston
Galveston, Texas, 775550435
Indiana Univ Hosp
Indianapolis, Indiana, 46202-5250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, 46202
Wishard Hosp
Indianapolis, Indiana, 46202
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, 32209
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, 900331079
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033
Univ of Miami (Pediatric)
Miami, Florida, 33161
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, 701122699
Beth Israel Med Ctr
New York, New York, 10003
Columbia Presbyterian Med Ctr
New York, New York, 10032
Univ of Pennsylvania
Philadelphia, Pennsylvania, 19104
Community Health Network, Inc
Rochester, New York, 14642-0001
St Mary's Hosp (Univ of Rochester/Infectious Diseases)
Rochester, New York, 14642
Univ of Rochester Medical Center
Rochester, New York, 14642
Univ of Washington
Seattle, Washington, 98104
Children's Hospital & Medical Center / Seattle ACTU
Seattle, Washington, 981050371
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, 13210
About this study
Official title: An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Between Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) and Selected Protease Inhibitor (PI) and Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) Therapies Among HIV-Infected Women
The purpose of this study is to look at the level of depo-medroxyprogesterone acetate (DMPA or Depo-Provera) in the blood to see if is affected by certain anti-HIV drugs (nelfinavir [NFV], efavirenz [EFV], indinavir [IDV] in combination with ritonavir [RTV], and nevirapine [NVP]). This study will also look at the levels of these anti-HIV drugs to see if they are affected by DMPA.
DMPA is a hormonal birth control method that is given as an injection. It is not known if taking DMPA together with anti-HIV drugs changes the amount of DMPA and/or the amount of anti-HIV drugs in the blood. If higher levels of DMPA occur, side effects may increase. If lower levels of anti-HIV drugs occur, the drugs may become less effective against HIV. This study will look at the levels of anti-HIV drugs and DMPA in the blood when these medications are used together.
Read the detailed description
DMPA, an injectable depot formulation of medroxyprogesterone (MPA), is a commonly used form of "progestin-only" contraception. Information is limited on the specific P450 isozymes that metabolize MPA; however, it appears that CYP3A4 is 1 pathway of hepatic clearance. Drugs known to be inhibitors of the CYP3A4 pathway (such as protease inhibitors [PIs]) may lead to elevated concentrations of MPA. Secondly, MPA given as DMPA injections has been shown to induce the activity of CYP3A4 by 25 percent. It is possible that this action may result in enhanced clearance of the substrates of CYP3A4, including PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), which in turn may result in reduced drug exposure and possible ARV failure. This study is designed to address the lack of information on potential interactions between PIs or NNRTIs and DMPA.
Patients are enrolled into 1 of 5 arms based on their current ARV regimen:
Arm A (control group): No current ARVs or receiving nucleoside reverse transcriptase inhibitors (NRTIs) only.
Arm B: NFV (1250 mg bid or 750 mg tid) in combination with NRTIs. Arm C: EFV (600 mg qd) in combination with NRTIs. Arm D: IDV (800 mg bid) and RTV (100 mg bid or 200 mg bid) in combination with NRTIs.
Arm E: NVP (200 mg bid) in combination with NRTIs. Acceptable NRTIs and any fixed combination of these medications include: zidovudine (ZDV), lamivudine, didanosine, stavudine (d4T), zalcitabine, and abacavir; concurrent therapy using ZDV and d4T is not allowed. ARV therapy is not provided by this study. One dose of DMPA is provided to all patients at entry (Day 0) and an optional dose of DMPA will be available at the final visit (Week 12) for those who are interested in continuing with DMPA outside of the protocol and who do not experience adverse events from the first DMPA injection. Patients in Arms B, C, D, and E have intensive pharmacokinetic sampling done at entry and at Week 4 to measure ARV levels. All patients have blood tests at Weeks 2, 4, 6, 8, 10, and 12 to measure levels of DMPA and progesterone. In addition, tests to monitor HIV-1 RNA levels, CD4 and CD8 counts, hematology, blood chemistries, and liver function are performed periodically.
- Conditions
- HIV Infections
- Being tested
- Indinavir sulfate, Ritonavir, Nelfinavir mesylate, Efavirenz, Nevirapine
- Keywords
- Delayed-Action Preparations, Drug Interactions, Drug Therapy, Combination, Nevirapine, HIV Protease Inhibitors, Ritonavir, Indinavir, Nelfinavir, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Pharmacokinetics, Medroxyprogesterone 17-Acetate, efavirenz
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indinavir sulfateDrug
RitonavirDrug
Nelfinavir mesylateDrug
EfavirenzDrug
NevirapineDrug
Medroxyprogesterone acetateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study startJun 2001
- Study completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Enrolment
- 76 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Investigators
- Susan Cohn, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00016601
- Sponsor's protocol ID
- A5093
- Other IDs
- ACTG A5093
- Status last verified
- Oct 2012
- First submitted
- 18 May 2001
- Last updated
- 2 Nov 2012
- Results posted
- No
Publications
Watts DH, Park JG, Cohn SE, Yu S, Hitti J, Stek A, Clax PA, Muderspach L, Lertora JJ. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008 Feb;77(2):84-90. doi: 10.1016/j.contraception.2007.10.002. Epub 2007 Dec 21.
PubMed 18226670
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Between Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) and Selected Protease Inhibitor (PI) and Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) Therapies Among HIV-Infected Women
- ClinicalTrials.gov ID
- NCT00016601
- Acronym / sponsor ID
- A5093
- Conditions
- HIV Infections
- Keywords
- Delayed-Action Preparations, Drug Interactions, Drug Therapy, Combination, Nevirapine, HIV Protease Inhibitors, Ritonavir, Indinavir, Nelfinavir
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jun 2001
- Study completion
- May 2004 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look at the level of depo-medroxyprogesterone acetate (DMPA or Depo-Provera) in the blood to see if is affected by certain anti-HIV drugs (nelfinavir [NFV], efavirenz [EFV], indinavir [IDV] in combination with ritonavir [RTV], and nevirapine [NVP]). This study will also look at the levels of these anti-HIV drugs to see if they are affected by DMPA.
DMPA is a hormonal birth control method that is given as an injection. It is not known if taking DMPA together with anti-HIV drugs changes the amount of DMPA and/or the amount of anti-HIV drugs in the blood. If higher levels of DMPA occur, side effects may increase. If lower levels of anti-HIV drugs occur, the drugs may become less effective against HIV. This study will look at the levels of anti-HIV drugs and DMPA in the blood when these medications are used together.
Detailed description
DMPA, an injectable depot formulation of medroxyprogesterone (MPA), is a commonly used form of "progestin-only" contraception. Information is limited on the specific P450 isozymes that metabolize MPA; however, it appears that CYP3A4 is 1 pathway of hepatic clearance. Drugs known to be inhibitors of the CYP3A4 pathway (such as protease inhibitors [PIs]) may lead to elevated concentrations of MPA. Secondly, MPA given as DMPA injections has been shown to induce the activity of CYP3A4 by 25 percent. It is possible that this action may result in enhanced clearance of the substrates of CYP3A4, including PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), which in turn may result in reduced drug exposure and possible ARV failure. This study is designed to address the lack of information on potential interactions between PIs or NNRTIs and DMPA.
Patients are enrolled into 1 of 5 arms based on their current ARV regimen:
Arm A (control group): No current ARVs or receiving nucleoside reverse transcriptase inhibitors (NRTIs) only.
Arm B: NFV (1250 mg bid or 750 mg tid) in combination with NRTIs. Arm C: EFV (600 mg qd) in combination with NRTIs. Arm D: IDV (800 mg bid) and RTV (100 mg bid or 200 mg bid) in combination with NRTIs.
Arm E: NVP (200 mg bid) in combination with NRTIs. Acceptable NRTIs and any fixed combination of these medications include: zidovudine (ZDV), lamivudine, didanosine, stavudine (d4T), zalcitabine, and abacavir; concurrent therapy using ZDV and d4T is not allowed. ARV therapy is not provided by this study. One dose of DMPA is provided to all patients at entry (Day 0) and an optional dose of DMPA will be available at the final visit (Week 12) for those who are interested in continuing with DMPA outside of the protocol and who do not experience adverse events from the first DMPA injection. Patients in Arms B, C, D, and E have intensive pharmacokinetic sampling done at entry and at Week 4 to measure ARV levels. All patients have blood tests at Weeks 2, 4, 6, 8, 10, and 12 to measure levels of DMPA and progesterone. In addition, tests to monitor HIV-1 RNA levels, CD4 and CD8 counts, hematology, blood chemistries, and liver function are performed periodically.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Are HIV-positive.
- Have plasma HIV-1 RNA (level of HIV in the blood) below 10,000 copies/ml within 30 days before study entry.
- Had their last menstrual period (LMP) less than 35 days before study entry.
- Have serum follicle-stimulating hormone below 40 MIU/ml if their LMP occurred more than 35 days before study entry.
- Have been on the same anti-HIV drugs for at least 30 days before study entry, if taking anti-HIV drugs. If not taking anti-HIV drugs, patients must have been told about anti-HIV drugs within the 3 months before study entry and have chosen not to take them now or in the future.
Key exclusion criteria (21 listed)
- Have taken anti-HIV drugs within 30 days before study entry but have chosen not to take them.
- Are taking only 1 NRTI.
- Are taking anti-HIV drugs other than those listed in the treatment groups, including tenofovir, amprenavir, and lopinavir/ritonavir, or have taken tenofovir, amprenavir, or lopinavir/ritonavir within 30 days before study entry.
- Have taken ZDV and d4T together within 30 days before study entry.
- Are not able to take the anti-HIV drugs properly while on the study, in the opinion of the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indinavir sulfate | Drug | – |
| Ritonavir | Drug | – |
| Nelfinavir mesylate | Drug | – |
| Efavirenz | Drug | – |
| Nevirapine | Drug | – |
| Medroxyprogesterone acetate | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2012.
- Results publication: PubMed 18226670Watts DH, Park JG, Cohn SE, Yu S, Hitti J, Stek A, Clax PA, Muderspach L, Lertora JJ. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008 Feb;77(2):84-90. doi: 10.1016/j.contraception.2007.10.002. Epub 2007 Dec 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Cohn study chair
32 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Indinavir sulfate, Ritonavir and Nelfinavir mesylate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 32 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 21 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 2 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00016601, which also lists 1 linked publication.
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 2 Nov 2012.