Study to Evaluate the Effects of Underlying Renal or Hepatic Dysfunction on the Pharmacokinetics of Nevirapine

An Open-Label, Single Dose Study to Evaluate the Effects of Underlying Renal or Hepatic Dysfunction on the Pharmacokinetics of Nevirapine (VIRAMUNE®)

Study to assess the effects of varying degrees of renal dysfunction and hepatic insufficiency on the single-dose pharmacokinetics of nevirapine and nevirapine metabolites in order to establish an appropriate dose and/or dosing frequency for renally- and hepatically-impaired patients

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Renal Insufficiency
• Intervention / Treatment: Drug: Nevirapine

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients of any race between the ages of 18 and 75 years with weight within 30% of normal for gender, height and frame as specified by the Metropolitan Life Insurance Table

• For patients in the renal group: stable creatinine clearance based on two estimations taken at least 3 days apart, corresponding to one of four groups:

  • Group 1 (mild dysfunction) = 50 ml/min <= Creatinine Clearance (CLcr) < 80 ml/min
  • Group 2 (moderate dysfunction) = 30 ml/min <= CLcr < 50 ml/min
  • Group 3 (severe dysfunction) = CLcr < 30 ml/min and
  • Group 4 = end-stage renal disease (ESRD) requiring dialysis

• For patients in the hepatic group

  • Two baseline creatinine clearances (taken at least 3 days apart) > 80 ml/min
  • clinically diagnosed with hepatic insufficiency and Class A or B liver disease according to Child-Pugh's Classification; subjects must have a Child-Pugh score of 5-9 points

• For patients in the normal group, i.e. normal with respect to hepatic and renal function

  • matched with hepatic group regarding gender, age (+- 10 years), weight (+- 30 pounds) and smoking history
  • Two baseline creatinine clearances (taken at least 3 days apart) > 80 ml/min
  • No abnormalities on clinical or laboratory evaluations
• Female patients of childbearing potential must be willing to use a reliable form of contraception which must include a medically approved form of barrier contraception
• Patients who are able to provide written consent and comply with study requirements

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Seated systolic blood pressure either < 100 mmHg or > 150 mmHg and/or heart rate either < 50 beats/min or > 90 beats/min
• History of any illness or drug allergy that in the opinion of the investigator might confound the results of the study or pose additional risk in administering nevirapine to the subject
• Patients who have had an acute illness or hospitalization other than for routine dialysis within 2 weeks prior to study initiation
• Patients who are currently taking any over-the-counter drug within 3 days prior to study initiation, or who are currently taking any prescription drug that in the opinion of the investigator in consultation with Boehringer Ingelheim Pharmaceuticals Incorporated (BIPI) medical monitor and pharmacokineticist might interfere with the absorption, distribution or metabolism on the test drug
• Significant electrocardiogram (ECG) abnormalities

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nevirapine; Single dose administration	Drug: Nevirapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC (Area under the plasma concentration time curve)	up to 7 days
Cmax (Maximum observed concentration of the analyte in plasma)	up to 7 days
Tmax (Time of maximum concentration of the analyte in plasma)	up to 7 days
T1/2 (Terminal half-life of the analyte in plasma)	up to 7 days
Vss/F (Volume of Distribution)	up to 7 days
MRT (Mean residence time of the analyte)	up to 7 days
CL/F (Apparent clearance of the analyte in plasma)	up to 7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 21 days
Number of patients with abnormal changes in laboratory parameters	Screening, Day 0, Day 7

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 1999
• Primary Completion (Actual): July 1, 1999
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 9, 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: Digestive System Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Renal Insufficiency; 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: 1100.1259

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