Drug Interactions Between Lopinavir/Ritonavir and Oral or Patch Contraceptives in HIV Infected Women - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00125983

Purpose

The purpose of this study is to examine the drug interactions between a protease inhibitor (PI)-based regimen including lopinavir/ritonavir (LPV/r) and two forms of contraceptive medications in HIV infected women.

Condition	Intervention	Phase
HIV Infections Pregnancy	Drug: Lopinavir/ritonavir Drug: Ortho Novum 1/35 Drug: Ortho Evra	Phase II

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study
Official Title:	A Phase II Pharmacokinetic Study of the Transdermal Contraceptive System and Oral Contraceptive in HIV-1 Infected Women on Lopinavir/Ritonavir

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS and Pregnancy

Drug Information available for: Modicon Ritonavir Lopinavir Ortho Evra Norinyl

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Days 17, 18, 19, and 24 Ortho Evra transdermal contraceptive ethinyl estradiol (EE) area under the concentration-time curve (AUC)

Secondary Outcome Measures:

Intensive EE AUC pharmacokinetics (PK) after single dose Ortho Novum (ON) 1/35 and after Ortho Evra administration on Days 17, 18, 19, and 24
Day 1 intensive EE AUC PK after single dose ON 1/35
Days 17, 18, 19, and 24 norelgestromin (NGMN) AUC
changes in HIV RNA viral load, CD4 and CD8 counts and their respective percentages, sex hormone binding globulin levels, and liver enzymes from baseline to Days 17, 18, 19, and 24
occurrence of nausea and vomiting, breast tenderness, headache, skin irritation, vaginal bleeding, change in weight, change in blood pressure, change in appetite, mood changes, vaginal infection, and gallbladder disease
PK parameters of LPV in Arm A at baseline and on Days 17, 18, 19, and 24

Estimated Enrollment:	54
Study Completion Date:	January 2007

Detailed Description:

Both PIs and oral contraceptives are metabolized by the same pathway, which significantly decreases the effectiveness of oral contraceptives and limits the contraceptive choices available to HIV infected women. More effective hormonal contraceptive methods are necessary for preventing unintended pregnancy in women taking highly active antiretroviral therapy (HAART). Ortho Evra is a contraceptive patch that was approved by the FDA in 2001; it uses a transdermal contraceptive system, and higher rates of compliance have been associated with its use, compared to oral contraceptives. Because Ortho Evra is administered as a contraceptive patch worn on the skin, it may bypass the metabolic pathway common to both PIs and oral contraceptives, making it a viable contraceptive option for HIV infected women on PI-based regimens. The purpose of the study is to examine the interaction between a PI-based regimen containing LPV/r and two forms of contraceptive medications, Ortho Evra and an oral contraceptive, Ortho Novum (ON 1/35), in HIV infected women.

Participants will be enrolled in this study for 6 weeks and will be assigned to one of two study arms, depending on their HAART regimen at study entry. Participants in both arms will also be stratified by age. Arm A participants will receive 400 mg/100 mg LPV/r twice daily along with two or more nucleoside reverse transcriptase inhibitors (NRTIs). Arm B participants will receive a regimen containing only NRTIs or no HAART. HAART will not be provided by this study. All patients will receive a single dose of ON 1/35 on Day 1 and will start the Ortho Evra contraceptive patch on Day 3. A physical exam, pap smear, pregnancy test, viral load test, CD4 and CD8 counts, and blood collection will occur at or before study entry and on Day 24. Pharmacokinetic analyses will occur on Days 1 through 3, 17 through 19, and 24.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for All Participants:

HIV infected
CD4 count of 200 cells/mm3 or more within 45 days of study entry
HIV-1 RNA viral load less than 55,000 copies/ml within 45 days of study entry
Parent or guardian willing to provide informed consent
Negative pregnancy test within 45 days of study entry
Willing to use acceptable forms of contraception
Agrees not to change current smoking or non-smoking habits
Agrees not to consume caffeine on Day 1, Days 17 through 19, and Day 24 until after the last blood sample of that day is drawn
Agrees not to consume alcohol within 48 hours of PK sampling periods
Patients on methadone maintenance therapy should be on a stable methadone dose for at least 60 days prior to study entry and continue maintenance therapy throughout the study

Inclusion Criteria for Arm A Participants:

Have taken LPV/r for at least 60 consecutive days prior to study entry and taken the same dose twice daily for at least 14 days prior to study entry. Women switching from capsule formulation LPV/r to new tablet formulation of 200mg/50 mg LPV/r must be taking twice-daily doses of this formulation, for a total daily dose of 800 mg/200 mg LPV/r, for at least 7 days prior to study entry.

Inclusion Criteria for Arm B Participants:

Have not taken or currently not taking a PI- or non-nucleoside reverse transcriptase inhibitors (NNRTI-) based regimen for at least 30 days prior to study entry, and not planning on starting PIs or NNRTIs during the 6-week study period. Women who have not been on HAART for at least 30 days prior to study entry are also eligible.
For patients not receiving HAART, documentation that they have been counseled about the benefits of HIV treatment within 90 days of study entry and have elected not to initiate therapy

Exclusion Criteria for All Participants:

Use of systemic hormonal therapies containing estrogens, progestins, or anabolic steroids (e.g., estrogen, progesterone, oral contraceptives, Mirena [levonorgestrol] intrauterine device [IUD], Progestasert [progesterone] IUD) within 60 days of study entry
Anabolic therapies (nandrolone decanoate or megestrol) within 60 days of study entry
Systemic glucocorticoids within 14 days of study entry
Certain medical conditions. More information on this criterion can be found in the protocol.
Need for prolonged bedrest after major surgery
Smokers of ages 35 or older
NNRTIs within 30 days of study entry
Nausea, vomiting, or abdominal pain of Grade 3 or higher within 30 days of study entry
Known allergy or sensitivity to ethinyl estradiol (EE), norelgestromin (NGMN), or components of the Ortho Evra contraceptive patch
Known allergy or sensitivity to norethindrone or components of the ON 1/35 oral contraceptive pill
Serious illness requiring systemic treatment or hospitalization within 14 days of study entry
Undiagnosed abnormal vaginal bleeding
Depo-Provera (medroxyprogesterone acetate) within 180 days of study entry
Lunelle (estradiol cypionate and medroxyprogesterone acetate) within 90 days of study entry
Use of certain medications within 30 days of study entry
Current drug or alcohol use or dependence that, in the opinion of the investigator, may interfere with the study
Unable to adhere to HAART, the Ortho Evra contraceptive patch, or single dose ON 1/35 regimens

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125983

Locations

United States, California
Los Angeles County Medical Center/USC
Los Angeles, California, United States, 90033
University of Southern California
Los Angeles, California, United States, 90033-1079
United States, Colorado
University of Colorado Health Sciences Center, Denver
Denver, Colorado, United States, 80262-3706
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06504
United States, Florida
University of Florida - Health Science Center
Jacksonville, Florida, United States, 32209
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96816-2396
United States, Illinois
Womens & Childrens HIV Program
Chicago, Illinois, United States, 60608-1797
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202-5250
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8106
United States, New York
The Cornell Clinical Trials Unit
New York, New York, United States, 10021
Chelsea Clinic
New York, New York, United States, 10011
Beth Israel Medical Center
New York, New York, United States, 10003
Weill Med. College of Cornell Univ.
New York, New York, United States, 10021
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Washington
University of Washington (Seattle)
Seattle, Washington, United States, 98104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:

Lori Kamemoto, MD, MPH

Hawaii AIDS Clinical Research Program, University of Hawaii School of Medicine

More Information

Additional Information:

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

Publications:

Mildvan D, Yarrish R, Marshak A, Hutman HW, McDonough M, Lamson M, Robinson P. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):471-7.

Ouellet D, Hsu A, Qian J, Locke CS, Eason CJ, Cavanaugh JH, Leonard JM, Granneman GR. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Br J Clin Pharmacol. 1998 Aug;46(2):111-6.

Audet MC, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, Creasy GW; ORTHO EVRA/EVRA 004 Study Group. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA. 2001 May 9;285(18):2347-54.

Study ID Numbers:	ACTG A5188, DAIDS-ES ID 10011
Study First Received:	July 29, 2005
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00125983 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Birth Control Pills
Oral Contraceptives
Contraceptive Patch
Pharmacokinetics
Antiretroviral Therapy, Highly Active

Protease Inhibitor
Treatment Experienced
Treatment Naive
Contraception

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Modicon
Molecular Mechanisms of Pharmacological Action
Contraceptive Agents
Contraceptives, Oral
Physiological Effects of Drugs
Contraceptive Agents, Female
Reproductive Control Agents
Infection
Contraceptives, Oral, Sequential
Anti-Retroviral Agents
Lopinavir
Therapeutic Uses

Contraceptives, Oral, Synthetic
Ortho Evra
Retroviridae Infections
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Norinyl
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2009