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
Results First Received: July 28, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infections
Hepatic Impairment
Intervention: Drug: efavirenz containing antiretroviral regimen

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
21 participants were enrolled in the study; 5 discontinued prior to study drug administration (1 adverse event, 1 enrollment completed, 1 screen failure, 1 no longer met study criteria and 1 withdrew consent).

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Participant Flow:   Overall Study
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
STARTED     6 [1]   2 [1]   1 [1]   7 [2]
COMPLETED     6     2     1     6  
NOT COMPLETED     0     0     0     1  
Participant no longer met study criteria                 0                 0                 0                 1  
[1] Treated on Day 1
[2] Treated on Day 1. One participant enrolled twice in the study and is hence counted twice



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group
Total Total of all reporting groups

Baseline Measures
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function     Total  
Number of Participants  
[units: participants]
  6     2     1     7     16  
Age  
[units: years]
Mean ± Standard Deviation
  50  ± 11     51  ± 1     47     49  ± 4     49  ± 7  
Age, Customized  
[units: participants]
         
< 65 years     5     2     1     7     15  
>= 65 years     1     0     0     0     1  
Gender  
[units: participants]
         
Female     4     0     1     0     5  
Male     2     2     0     7     11  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     1     0     1     0     2  
Not Hispanic or Latino     5     2     0     6     13  
Unknown or Not Reported     0     0     0     1     1  
Race/Ethnicity, Customized  
[units: participants]
         
American Indian     1     0     0     0     1  
Black     3     1     0     5     9  
White     2     1     0     2     5  
Hispanic/Latino     0     0     1     0     1  
Body mass index (BMI) Continuous [1]
[units: kg/m^2]
Mean ± Standard Deviation
  26.3  ± 3.7     24.6  ± 0.1     24.0     22.8  ± 2.2     24.4  ± 3.0  
Height Continuous  
[units: cm]
Mean ± Standard Deviation
  165.5  ± 11.9     173.4  ± 3.7     160.0     175.6  ± 7.2     170.6  ± 10.0  
Weight, Continuous  
[units: kilogram]
Mean ± Standard Deviation
  71.5  ± 7.2     73.9  ± 2.9     61.5     70.4  ± 9.6     70.7  ± 7.9  
[1] BMI is defined as the individual's body weight divided by the square of his or her height.



  Outcome Measures
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1.  Primary:   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. ]

Measure Type Primary
Measure Title Maximum Plasma Concentration (Cmax)
Measure Description Cmax was obtained directly from the concentration-time data.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed per protocol.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     6  
Maximum Plasma Concentration (Cmax)  
[units: micrograms (mcg)/mL]
Geometric Mean ( Full Range )
  5.303  
  ( 2.730 to 16.000 )  
  8.964  
  ( 4.900 to 16.400 )  
  6.750  
  ( 6.750 to 6.750 )  
  6.515  
  ( 2.680 to 25.300 )  

No statistical analysis provided for Maximum Plasma Concentration (Cmax)



2.  Primary:   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. ]

Measure Type Primary
Measure Title Minimum Plasma Concentration (Cmin)
Measure Description Cmin was obtained directly from the concentration-time data.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed per protocol.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     6  
Minimum Plasma Concentration (Cmin)  
[units: mcg/mL]
Geometric Mean ( Full Range )
  2.599  
  ( 0.688 to 11.500 )  
  4.885  
  ( 1.850 to 12.900 )  
  3.780  
  ( 3.780 to 3.780 )  
  2.405  
  ( 0.611 to 17.900 )  

No statistical analysis provided for Minimum Plasma Concentration (Cmin)



3.  Primary:   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. ]

Measure Type Primary
Measure Title Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])
Measure Description The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed per protocol.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     1     1     6  
Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])  
[units: mcg*h/mL]
Geometric Mean ( Full Range )
  83.422  
  ( 29.84 to 323.06 )  
  75.425  
  ( 75.425 to 75.425 )  
  101.912  
  ( 101.912 to 101.912 )  
  93.516  
  ( 36.51 to 486.43 )  

No statistical analysis provided for Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])



4.  Primary:   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. ]

Measure Type Primary
Measure Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measure Description Tmax was obtained directly from the concentration-time data.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed per protocol.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     6  
Time to Reach Maximum Observed Plasma Concentration (Tmax)  
[units: hours]
Median ( Full Range )
  1.765  
  ( 0.98 to 6.03 )  
  4.500  
  ( 3.00 to 6.00 )  
  1.000  
  ( 1.00 to 1.00 )  
  3.500  
  ( 2.00 to 6.00 )  

No statistical analysis provided for Time to Reach Maximum Observed Plasma Concentration (Tmax)



5.  Secondary:   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. ]

Measure Type Secondary
Measure Title Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
Measure Description 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.
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.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All data from participants who signed the informed consent and enrolled in the study is included in the data set used for evaluating SAEs.

Reporting Groups
  Description
Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group
Participants Not Dosed Participants were enrolled in the study and discontinued prior to study drug administration

Measured Values
    Participants With Mild Hepatic Impairment     Participants With Moderate Hepatic Impairment     Participants With Severe Hepatic Impairment     Participants With Normal Hepatic Function     Participants Not Dosed  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7     5  
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)  
[units: Participants]
         
Deaths     0     0     0     0     1  
Other Serious Adverse Events     0     0     0     0     1  

No statistical analysis provided for Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)



6.  Secondary:   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). ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced AEs
Measure Description 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.
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).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants Who Experienced AEs  
[units: participants]
  1     0     0     0  

No statistical analysis provided for Number of Participants Who Experienced AEs



7.  Secondary:   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). ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation
Measure Description 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.
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).  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation  
[units: participants]
  0     0     0     0  

No statistical analysis provided for Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation



8.  Secondary:   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. ]

Measure Type Secondary
Measure Title Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Measure Description 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.
Time Frame Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 and were evaluated for these measures.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  5     2     1     7  
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements  
[units: participants]
       
Low platelet count     0     1     0     0  
Low leukocytes     1     0     0     1  
Low neutrophils+bands (absolute)     1     2     1     0  
Low lymphocytes (absolute)     0     0     1     0  

No statistical analysis provided for Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements



9.  Secondary:   Number of Participants With Serum Chemistry MAs   [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ]

Measure Type Secondary
Measure Title Number of Participants With Serum Chemistry MAs
Measure Description 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.
Time Frame Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis. The 'n' signifies those participants who received study drug and were evaluated for this measure, for each group respectively.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants With Serum Chemistry MAs  
[units: participants]
       
High bilirubin (total) (n = 5, 1, 1, 7)     1     0     0     0  
High creatinine (n = 5, 1, 1, 7)     0     0     0     1  
Low albumin (n = 5, 1, 1, 7)     0     1     0     0  
High amylase (total) (n = 5, 1, 0, 7)     0     0     0     1  

No statistical analysis provided for Number of Participants With Serum Chemistry MAs



10.  Secondary:   Number of Participants With Urinalysis MAs   [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ]

Measure Type Secondary
Measure Title Number of Participants With Urinalysis MAs
Measure Description 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+).
Time Frame Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 and were evaluated for these measures.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  5     1     1     7  
Number of Participants With Urinalysis MAs  
[units: participants]
       
White blood cells (WBCs)     1     0     0     0  
Red blood cells (RBCs)     1     0     0     0  

No statistical analysis provided for Number of Participants With Urinalysis MAs



11.  Secondary:   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) ]

Measure Type Secondary
Measure Title Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
Measure Description 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.
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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities  
[units: participants]
  3     1     0     5  

No statistical analysis provided for Number of Participants With Identified Electrocardiogram (ECG) Abnormalities



12.  Secondary:   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) ]

Measure Type Secondary
Measure Title Number of Participants With Clinically Meaningful Vital Signs Measures
Measure Description 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.
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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants With Clinically Meaningful Vital Signs Measures  
[units: participants]
  0     0     0     0  

No statistical analysis provided for Number of Participants With Clinically Meaningful Vital Signs Measures



13.  Secondary:   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) ]

Measure Type Secondary
Measure Title Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)
Measure Description 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
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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received study drug on Day 1 were included in the analysis. Physical examination findings were not analysed at discharge.

Reporting Groups
  Description
EFV600mg Participants With Mild Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Mild hepatic impairment (grade A) is defined as a Child-Pugh (CP) total score of 5-6. The CP classification assesses 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy) on a scale of 1 (mild or none) to 3 (most severe). Total score range is 5 (mild) to 15 (severe).
EFV600mg Participants With Moderate Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Moderate hepatic impairment (grade B) is defined as a CP total score of 7-9.
EFV600mg Participants With Severe Hepatic Impairment Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz, either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM), on an empty stomach. The duration of efavirenz administration was 2 days and participants were admitted to the clinical facility for this period. Participants who were on an off-label reduced dose of efavirenz (eg, 400 mg) continued on the reduced dose. Severe hepatic impairment (grade C) is defined as a CP total score of 10-15.
EFV600mg Participants With Normal Hepatic Function Participants were administered a dose of 600 mg once daily (capsules or tablets) of efavirenz either in the morning (at approximately 9:00 AM) or before bed time (at approximately 9:00 PM) on an empty stomach. The duration of efavirenz administration was 2 days when participants were admitted to the clinical facility. Participants were enrolled after at least 6 participants with hepatic impairment had completed. One participant enrolled twice in the study and is hence counted twice in this group

Measured Values
    EFV600mg Participants With Mild Hepatic Impairment     EFV600mg Participants With Moderate Hepatic Impairment     EFV600mg Participants With Severe Hepatic Impairment     EFV600mg Participants With Normal Hepatic Function  
Number of Participants Analyzed  
[units: participants]
  6     2     1     7  
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)  
[units: participants]
  5     2     1     5  

No statistical analysis provided for Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early leading to a small number of participants treated and analyzed. Due to the small sample size, no conclusion could be made for participants with Child-Pugh scores B and C (moderate and severe hepatic impairment).


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


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