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

NCT00125983 | Completed Phase 2

• 3 other identifiers: A518810011AACTG A5188
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

HIV Infections; Pregnancy

Keywords

Birth Control Pills; Oral Contraceptives; Contraceptive Patch; Pharmacokinetics; Antiretroviral Therapy, Highly Active; Protease Inhibitor; Treatment Experienced; Treatment Naive; Contraception

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (6)

• 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

Interventions

Lopinavir/ritonavir DRUG

Ortho Novum 1/35 DRUG

Ortho Evra DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (9)

USC CRS

Los Angeles, California, 90033-1079, United States

Location

Usc La Nichd Crs

Los Angeles, California, 90033, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816-2396, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202-5250, United States

Location

Beth Israel Med. Ctr., ACTU

New York, New York, 10003, United States

Location

Weill Med. College of Cornell Univ., The Cornell CTU

New York, New York, 10021, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, United States

Location

San Juan City Hosp. PR NICHD CRS

San Juan, Puerto Rico

Location

Related Publications (4)

• 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. doi: 10.1097/00126334-200204150-00007.

  PMID: 11981363 BACKGROUND

• 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. doi: 10.1046/j.1365-2125.1998.00749.x.

  PMID: 9723818 BACKGROUND

• 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. doi: 10.1001/jama.285.18.2347.

  PMID: 11343482 BACKGROUND

• Vogler MA, Patterson K, Kamemoto L, Park JG, Watts H, Aweeka F, Klingman KL, Cohn SE. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010 Dec;55(4):473-82. doi: 10.1097/QAI.0b013e3181eb5ff5.

  PMID: 20842042 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir; ovcon 35; Ortho Evra

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lori Kamemoto, MD, MPH

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2005
• First Posted: August 2, 2005
• Study Completion: January 1, 2007
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (8); PR (1)