Drug Interactions Between Lopinavir/Ritonavir and Oral or Patch Contraceptives in HIV Infected Women

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00125983
First received: July 29, 2005
Last updated: May 17, 2012
Last verified: May 2012
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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:


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

Enrollment: 32
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Usc La Nichd Crs
Los Angeles, California, United States, 90033
USC CRS
Los Angeles, California, United States, 90033-1079
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816-2396
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202-5250
United States, New York
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, United States, 10021
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico
Sponsors and Collaborators
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:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00125983     History of Changes
Other Study ID Numbers: A5188, 10011, AACTG A5188
Study First Received: July 29, 2005
Last Updated: May 17, 2012
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Contraceptive Agents
Contraceptives, Oral
Ethynylestradiol mixture with norethindrone
Lopinavir
Norinyl
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Contraceptive Agents, Female
Contraceptives, Oral, Combined
Contraceptives, Oral, Hormonal
Contraceptives, Oral, Sequential
Contraceptives, Oral, Synthetic
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 29, 2014