Hepatic Insufficiency, Renal Insufficiency
Conditions
Brief summary
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
Interventions
DRUGNevirapine
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CL/F (Apparent clearance 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| Number of patients with abnormal changes in laboratory parameters | Screening, Day 0, Day 7 |
| Number of patients with adverse events | up to 21 days |
Outcome results
None listed