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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00162097
Recruitment Status : Completed
First Posted : September 13, 2005
Results First Posted : August 25, 2010
Last Update Posted : September 14, 2010
Sponsor:
Information provided by:
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE September 9, 2005
First Posted Date  ICMJE September 13, 2005
Results First Submitted Date  ICMJE July 28, 2010
Results First Posted Date  ICMJE August 25, 2010
Last Update Posted Date September 14, 2010
Study Start Date  ICMJE November 2004
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2010)
  • 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. ]
    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. ]
    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. ]
    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. ]
    Tmax was obtained directly from the concentration-time data.
Original Primary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2010)
  • 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. ]
    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). ]
    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). ]
    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. ]
    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. ]
    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. ]
    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) ]
    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) ]
    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) ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
To assess the safety of efavirenz in HIV-1 infected subjects, with or without hepatic impairment, on stable antiretroviral regimen containing efavirenz.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
Official Title  ICMJE Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV Infections
  • Hepatic Impairment
Intervention  ICMJE Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
  • Sustiva
  • BMS-561525
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 28, 2010)
21
Original Enrollment  ICMJE
 (submitted: September 9, 2005)
24
Actual Study Completion Date  ICMJE March 2008
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United States
Removed Location Countries Spain
 
Administrative Information
NCT Number  ICMJE NCT00162097
Other Study ID Numbers  ICMJE AI266-917
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Study Director, Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date September 2010

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