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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00162097
First received: September 9, 2005
Last updated: September 7, 2010
Last verified: September 2010

September 9, 2005
September 7, 2010
November 2004
March 2008   (final data collection date for primary outcome measure)
  • Maximum Plasma Concentration (Cmax) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Cmax was obtained directly from the concentration-time data.
  • Minimum Plasma Concentration (Cmin) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Cmin was obtained directly from the concentration-time data.
  • Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Tmax was obtained directly from the concentration-time data.
To assess steady-state PK of efavirenz in HIV-1 infected subjects on stable antiretroviral regimens containing efavirenz, and having selected degrees of hepatic impairment or normal hepatic function.
Complete list of historical versions of study NCT00162097 on ClinicalTrials.gov Archive Site
  • Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
    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 Who Experienced AEs Leading to Study Drug Discontinuation [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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 With Clinically Meaningful Vital Signs Measures [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    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
To assess the safety of efavirenz in HIV-1 infected subjects, with or without hepatic impairment, on stable antiretroviral regimen containing efavirenz.
Not Provided
Not Provided
 
Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Hepatic Impairment
Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
  • Sustiva
  • BMS-561525
  • Experimental: EFV600mg Participants With Mild Hepatic Impairment
    Intervention: Drug: efavirenz containing antiretroviral regimen
  • Experimental: EFV600mg Participants With Moderate Hepatic Impairment
    Intervention: Drug: efavirenz containing antiretroviral regimen
  • Experimental: EFV600mg Participants With Severe Hepatic Impairment
    Intervention: Drug: efavirenz containing antiretroviral regimen
  • Active Comparator: EFV600mg Participants With Normal Hepatic Function
    Intervention: Drug: efavirenz containing antiretroviral regimen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
March 2008
March 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Italy
 
NCT00162097
AI266-917
No
Study Director, Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP