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

Study Overview
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Brief Summary
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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

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

Conditions
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Renal Insufficiency, Hepatic Insufficiency

Intervention / Treatment
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* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nevirapine<br>Single dose administration | Drug: Nevirapine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |