Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment

HIV Infections Clinical Trial

Official title:

Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00162097
• Other study ID #: AI266-917
• Status: Completed
• Phase: Phase 1
• First received: September 9, 2005
• Last updated: September 7, 2010
• Start date: November 2004
• Est. completion date: March 2008

Study information

• Verified date: September 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Impairment
• HIV Infections
• Liver Diseases

Intervention

Drug:
• efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
• efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
• efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
• efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days

Locations

Country	Name	City	State
Italy	Local Institution	Milano
United States	Johns Hopkins University School Of Medicine	Baltimore	Maryland
United States	Virginia Commonwealth University Health Systems	Richmond	Virginia
United States	Uthscsa	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax)	Cmax was obtained directly from the concentration-time data.	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.	No
Primary	Minimum Plasma Concentration (Cmin)	Cmin was obtained directly from the concentration-time data.	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.	No
Primary	Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])	The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.	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.	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax was obtained directly from the concentration-time data.	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.	No
Secondary	Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)	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.	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.	Yes
Secondary	Number of Participants Who Experienced AEs	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.	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).	Yes
Secondary	Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation	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.	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).	Yes
Secondary	Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements	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	Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.	Yes
Secondary	Number of Participants With Serum Chemistry MAs	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	Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.	Yes
Secondary	Number of Participants With Urinalysis MAs	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+).	Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.	Yes
Secondary	Number of Participants With Identified Electrocardiogram (ECG) Abnormalities	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.	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)	Yes
Secondary	Number of Participants With Clinically Meaningful Vital Signs Measures	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.	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)	Yes
Secondary	Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)	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	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)	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form