Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine (VIRAMUNE) and Ethinyl Estradiol/Norethindrone in HIV-1 Infected Women

An Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine (VIRAMUNE® ) and Ethinyl Estradiol/Norethindrone [ORTHO-NOVUM® 1/35 (21 Pack)] in HIV-1 Infected Women

Study to determine the effects of nevirapine treatment on the pharmacokinetics of ethinyl estradiol (EE)/norethindrone (NET).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: EE/NET

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female patients between the ages of 18 and 65 years
• Plasma HIV-1 RNA <= 400 copies/mL, documenting HIV-1 infection, within 28 days prior to Study Day 0
• Lymphocytes Expressing CD4+ Surface Marker (CD4+ cell count) >= 100 cells/mm³ within 28 days prior to Study Day 0

• Patients who meet the following laboratory parameter:

  • Lymphocyte count >= 1000 cells/mm³
  • Hemoglobin >= 9.0 g/dl (men and women)
  • Platelet count >= 75000 cells/mm3
  • Alkaline Phosphatase <= 3.0 times the upper limit of normal
  • Serum Glutamic-Oxaloacetic Transaminase (SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) <= 3.0 times the upper limit of normal
  • Total bilirubin <= 1.5 times the upper limit of normal
  • Creatinine <= 2mg/dL
• Female patients of reproductive potential must be willing to use a reliable method of double-barrier contraception (such as diaphragm with spermicidal cream or jelly, or condoms with spermicidal foam)
• Patients who are informed of and willing and able to comply with the investigational nature of the study and had signed a written consent in accordance with institutional and federal guidelines
• Patients who have been on stable antiretroviral therapy (no changes in medication or dose) for at least thirty days prior to study entry and who will continue on background during study participation

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Patients requiring systemic treatment with corticosteroids or drugs known to be hepatic enzyme inducers or inhibitors within 14 days of stud entry (Study Day 0). Such substances in these categories include: macrolide antibiotics (erythromycin, clarithromycin), azole antifungals (ketoconazole, fluconazole, itraconazole) rifampin, rifabutin, and phenytoin
• Patients receiving any investigational drug within 30 days of the first dose of study medication and any antineoplastic agent or radiotherapy other than local skin radiotherapy treatment within 12 weeks before starting study medication
• Patients with malabsorption, severe chronic diarrhea or patients unable to maintain adequate oral intake
• Patients with a history of intravenous drug abuse, alcohol or substance abuse considered by the Investigator and Boehringer Ingelheim Pharmaceutical Incorporated (BIPI) Medical Monitor to be a significant impairment to health and compliance
• Patients undergoing treatment for an active infection
• Patients with hepatic insufficiency due to cirrhosis
• Patients with renal insufficiency
• Patients who are heavy smokers (e.g. > 20 cigarettes per day)
• Patients currently taking Norvir® (Ritonavir) or Rescriptor® (Delavirdine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nevirapine tablets; once a day (q.d.) Day 2-15, twice a day (b.i.d.) Study day 16-30	Drug: Nevirapine
Active Comparator: EE/NET tablets; Single dose on Study Day 0 and 30	Drug: EE/NET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC (Area under the plasma concentration time curve) of ethinyl estradiol/norethindrone (EE/NET)	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 0 and day 30
Cmax (maximum observed concentration) of EE/NET	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 0 and day 30
Tmax (Time of maximum concentration) of EE/NET	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 0 and day 30
AUCss (Area under the concentration time curve at steady state) of nevirapine	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 30
Cmax (maximum observed concentration) of nevirapine	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 30
Cmin (minimum observed concentration) of nevirapine	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 30
Cl/F (Oral clearance) of nevirapine	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 24, and 34 hours post dose on day 30

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 59 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): April 1, 1999
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 3, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 1100.1245

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No