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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Hepatic Impairment
Drug: efavirenz containing antiretroviral regimen
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 21
Study Start Date: November 2004
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EFV600mg Participants With Mild 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 Moderate 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 Severe Hepatic Impairment Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
  • Sustiva
  • BMS-561525
Active Comparator: EFV600mg Participants With Normal Hepatic Function Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
  • Sustiva
  • BMS-561525

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00162097

Locations
United States, Maryland
Johns Hopkins University School Of Medicine
Baltimore, Maryland, United States, 21287
United States, Texas
Uthscsa
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University Health Systems
Richmond, Virginia, United States, 23298
Italy
Local Institution
Milano, Italy, 20127
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00162097     History of Changes
Other Study ID Numbers: AI266-917
Study First Received: September 9, 2005
Results First Received: July 28, 2010
Last Updated: September 7, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Liver Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Digestive System Diseases
Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014