Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
- Conditions
- HIV InfectionsHepatic Impairment
- Interventions
- Registration Number
- NCT00162097
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of the study was to assess the steady-state pharmacokinetics (PK) of efavirenz (EFV) in human immunodeficiency virus type 1 (HIV-1) infected subjects on stable antiretroviral regimens containing EFV, and having selected degrees of hepatic impairment or normal hepatic function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- HIV-1 infection with or without Hepatitis B or C infection
- Stable antiretroviral regimen containing efavirenz and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) for at least 1 month
- Mild, moderate or severe hepatic impairment with hepatic cirrhosis
- Acute flare of hepatitis
- Positive pregnancy test for a female
- Significant acute medical illness in past 2 months
- Use of agents known to significantly affect liver metabolism
- Change in medications to treat a chronic disease in the past 2 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EFV600mg Participants With Normal Hepatic Function efavirenz containing antiretroviral regimen - EFV600mg Participants With Moderate Hepatic Impairment efavirenz containing antiretroviral regimen - EFV600mg Participants With Severe Hepatic Impairment efavirenz containing antiretroviral regimen - EFV600mg Participants With Mild Hepatic Impairment efavirenz containing antiretroviral regimen -
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose. The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
Maximum Plasma Concentration (Cmax) Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose. Cmax was obtained directly from the concentration-time data.
Minimum Plasma Concentration (Cmin) Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose. Cmin was obtained directly from the concentration-time data.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose. Tmax was obtained directly from the concentration-time data.
- Secondary Outcome Measures
Name Time Method Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing). AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product. Participants who discontinued the study due to an AE were recorded.
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Low platelet count: \<0.85 x lower limit of normal (LLN) (or if pre-treatment value \<LLN, then \<0.85 x pre-treatment value). Low leukocytes: \<0.9 x LLN (or if pre-treatment value \<LLN, then \<0.85 x pre-treatment value. If pre-treatment value \>upper limit of normal \[ULN\], then \<LLN). Low neutrophils+bands (absolute): \<=1.500 10\^3 cells/microliter (uL). Low lymphocytes (absolute): \<0.750 10\^3 cells/uL.
Number of Participants With Serum Chemistry MAs Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify the criteria for MAs in the data presented. High bilirubin (total): \>1.1 x ULN (or if pre-treatment value \>ULN, then \>1.25 x pre-treatment value). High creatinine: \>1.33 x pre-treatment value. Low albumin: \<0.9 x LLN (or if pre-treatment value \<LLN, then \<0.9 x pre-treatment value). High amylase (total): \>2 x pre-treatment value.
Number of Participants With Urinalysis MAs Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following urinalysis MA definitions specify the criteria for MAs in the data presented. The presence of white blood cells (WBCs) and red blood cells (RBCs) in the urine was graded on a scale: 0 = no cells present (negative); trace =a small number of cells present; then 1+, 2+, 3+ and 4+, denoting increasingly "positive" urine results (ie, WBCs/RBCs present in the urine). The MA for both WBCs and RBCs was \>= 2+ (or, if pre-treatment value \>=2+, then \>= 4+).
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing) ECG abnormalities are findings that are clinically meaningful by the judgment of the investigator. A 12-lead ECG was performed and all ECG recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed.
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing). Participants were monitored for SAEs up to 30 days after study discharge. An SAE was defined as any adverse event (AE) occurring at any dose that; resulted in death; was life threatening; resulted in a persistent or significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was a cancer; or was an overdose.
Number of Participants Who Experienced AEs From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing). AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product.
Number of Participants With Clinically Meaningful Vital Signs Measures From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing) Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. The investigator used his/her clinical judgement to decide whether or not abnormalities in vital signs were clinically meaningful.
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1) From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing) The physical examination included an evaluation of the participant's height and body mass index (BMI) (at screening only), and weight. Abnormal physical examination are findings that are clinically meaningful by the judgment of the investigator
Trial Locations
- Locations (4)
Local Institution
🇮🇹Milano, Italy
Uthscsa
🇺🇸San Antonio, Texas, United States
Johns Hopkins University School Of Medicine
🇺🇸Baltimore, Maryland, United States
Virginia Commonwealth University Health Systems
🇺🇸Richmond, Virginia, United States