Effects of Nevirapine on the Steady State Pharmacokinetics of Fluconazole in HIV Positive Patients

An Open-label Study in HIV+ Patients to Determine the Effects of Nevirapine (VIRAMUNE®) on the Steady State Pharmacokinetics of Fluconazole (DIFLUCAN®)

The purpose of this study was to determine the effects of nevirapine on the steady state pharmacokinetics of fluconazole and to assess the steady-state pharmacokinetics of nevirapine when given in combination with fluconazole.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients between the ages of 18 and 65 years who are seropositive for HIV-1 antibody by an ELISA test and confirmed by an alternative method, e.g. Western Blot
• CD4 + cell count ≥ 100 cells/mm3

• Patients who meet the following laboratory parameters

  • Granulocyte count > 1000 cells/mm3
  • Hemoglobin > 9.0 g/dl (men and women)
  • Platelet count > 75,000 cells/mm3
  • Alkaline phosphatase < 3.0 times the upper limit of normal
  • Aspartame Transaminase (AST) and Alanine Transaminase (ALT) < 3.0 times the upper limit of normal
  • Total bilirubin < 1.5 times the upper limit of normal
• Female patients of childbearing potential must be willing to use a reliable form of contraception which must include a medically approved from of barrier contraception
• Patients able to provide written informed consent and comply with study requirements

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Seated systolic blood pressure below 100 mmHg, or greater than 160 mmHg, and/or heart rate less than 50 or greater than 100 beats/min
• History of drug allergy or known drug hypersensitivity
• Patients receiving any investigational drug, antineoplastic agent or radiotherapy other than local skin radiotherapy treatment within 12 weeks before starting study medication
• Patients requiring systemic treatment with corticosteroids or drugs known to be hepatic enzyme inducers or inhibitors within 28 days of study entry (Study Day 1). Such substances in these categories include: macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin, dirithromycin), azole antifungals (e.g. itraconazole), rifabutin and phenytoin
• Patients requiring systemic treatment with CYP3A4 (cytochrome P450 3A4) substrates such as terfenadine, astemizole, cisapride, triazolam and midazolam during the course of the trial
• Use of protease inhibitors or non-nucleoside reverse transcriptase inhibitors within 28 days of Study Day 1 or during the trial
• Patients with a current history of intravenous drug abuse, alcohol or substance abuse (within the last year)
• History of any clinically important disease including hepatic, renal, cardiovascular or gastrointestinal disease
• Patients with malabsorption, severe chronic diarrhea or patients unable to maintain adequate oral intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fluconazole with and without Nevirapine	Drug: Nevirapine; Drug: Fluconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration of the analyte in plasma (Cmax)	up to day 40
Minimum concentration of the analyte in plasma (Cmin)	up to day 40
Area under the plasma concentration time curve over the dosing interval (AUCτ)	up to day 40

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 40 days
Time of Cmax (Tmax)	up to day 40
Oral clearance (Cl/F)	up to day 40
Number of patients with abnormal changes in laboratory parameters	up to day 40
Number of patients with clinically significant changes in vital signs	up to day 39

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (ACTUAL): July 1, 2001

Study Registration Dates

• First Submitted: July 2, 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; Physiological Effects of Drugs; 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Nevirapine; Fluconazole
• Other Study ID Numbers: 1100.1361