Hepatic Impairment, HIV Infections
Conditions
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.
Interventions
DRUGefavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 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) | 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]) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serum Chemistry MAs | 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 | 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 Who Died or Experienced Other Serious Adverse Events (SAEs) | 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 With Clinically Meaningful Vital Signs Measures | 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) | 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 |
| Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 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 Who Experienced AEs | 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 | 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 | 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. |
Countries
Italy, United States
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 6 |
| 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. | 2 |
| 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. | 1 |
| 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 | 7 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Participant no longer met study criteria | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|
| Age Continuous | 50 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 1 | 47 years | 49 years STANDARD_DEVIATION 4 | 49 years STANDARD_DEVIATION 7 |
| Age, Customized < 65 years | 5 participants | 2 participants | 1 participants | 7 participants | 15 participants |
| Age, Customized >= 65 years | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Body mass index (BMI) Continuous | 26.3 kg/m^2 STANDARD_DEVIATION 3.7 | 24.6 kg/m^2 STANDARD_DEVIATION 0.1 | 24.0 kg/m^2 | 22.8 kg/m^2 STANDARD_DEVIATION 2.2 | 24.4 kg/m^2 STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 0 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Height Continuous | 165.5 cm STANDARD_DEVIATION 11.9 | 173.4 cm STANDARD_DEVIATION 3.7 | 160.0 cm | 175.6 cm STANDARD_DEVIATION 7.2 | 170.6 cm STANDARD_DEVIATION 10 |
| Race/Ethnicity, Customized American Indian | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants | 1 participants | 0 participants | 5 participants | 9 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 2 participants | 1 participants | 0 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants | 7 Participants | 11 Participants |
| Weight, Continuous | 71.5 kilogram STANDARD_DEVIATION 7.2 | 73.9 kilogram STANDARD_DEVIATION 2.9 | 61.5 kilogram | 70.4 kilogram STANDARD_DEVIATION 9.6 | 70.7 kilogram STANDARD_DEVIATION 7.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 0 / 2 | 0 / 1 | 0 / 7 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 | 0 / 1 | 0 / 7 | 1 / 5 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])
The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
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.
Population: The analysis was performed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) | 83.422 mcg*h/mL |
| EFV600mg Participants With Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) | 75.425 mcg*h/mL |
| EFV600mg Participants With Severe Hepatic Impairment | Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) | 101.912 mcg*h/mL |
| EFV600mg Participants With Normal Hepatic Function | Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU]) | 93.516 mcg*h/mL |
Primary
Maximum Plasma Concentration (Cmax)
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.
Population: The analysis was performed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 5.303 micrograms (mcg)/mL |
| EFV600mg Participants With Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 8.964 micrograms (mcg)/mL |
| EFV600mg Participants With Severe Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 6.750 micrograms (mcg)/mL |
| EFV600mg Participants With Normal Hepatic Function | Maximum Plasma Concentration (Cmax) | 6.515 micrograms (mcg)/mL |
Primary
Minimum Plasma Concentration (Cmin)
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.
Population: The analysis was performed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Minimum Plasma Concentration (Cmin) | 2.599 mcg/mL |
| EFV600mg Participants With Moderate Hepatic Impairment | Minimum Plasma Concentration (Cmin) | 4.885 mcg/mL |
| EFV600mg Participants With Severe Hepatic Impairment | Minimum Plasma Concentration (Cmin) | 3.780 mcg/mL |
| EFV600mg Participants With Normal Hepatic Function | Minimum Plasma Concentration (Cmin) | 2.405 mcg/mL |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
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.
Population: The analysis was performed per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.765 hours |
| EFV600mg Participants With Moderate Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 4.500 hours |
| EFV600mg Participants With Severe Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.000 hours |
| EFV600mg Participants With Normal Hepatic Function | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.500 hours |
Secondary
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
An SAE was defined as any adverse event (AE) occurring at any dose that; resulted in death; was life threatening; resulted in a persistent or significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was a cancer; or was an overdose.
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.
Population: All data from participants who signed the informed consent and enrolled in the study is included in the data set used for evaluating SAEs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Other Serious Adverse Events | 0 Participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Other Serious Adverse Events | 0 Participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Other Serious Adverse Events | 0 Participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Other Serious Adverse Events | 0 Participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Deaths | 0 Participants |
| Participants Not Dosed | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Deaths | 1 Participants |
| Participants Not Dosed | Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs) | Other Serious Adverse Events | 1 Participants |
Secondary
Number of Participants Who Experienced AEs
AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product.
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).
Population: All participants who received study drug on Day 1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants Who Experienced AEs | 1 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants Who Experienced AEs | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants Who Experienced AEs | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants Who Experienced AEs | 0 participants |
Secondary
Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation
AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product. Participants who discontinued the study due to an AE were recorded.
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).
Population: All participants who received study drug on Day 1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation | 0 participants |
Secondary
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)
The physical examination included an evaluation of the participant's height and body mass index (BMI) (at screening only), and weight. Abnormal physical examination are findings that are clinically meaningful by the judgment of the investigator
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)
Population: All participants who received study drug on Day 1 were included in the analysis. Physical examination findings were not analysed at discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1) | 5 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1) | 2 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1) | 1 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1) | 5 participants |
Secondary
Number of Participants With Clinically Meaningful Vital Signs Measures
Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. The investigator used his/her clinical judgement to decide whether or not abnormalities in vital signs were clinically meaningful.
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)
Population: All participants who received study drug on Day 1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Clinically Meaningful Vital Signs Measures | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Clinically Meaningful Vital Signs Measures | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Clinically Meaningful Vital Signs Measures | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Clinically Meaningful Vital Signs Measures | 0 participants |
Secondary
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
ECG abnormalities are findings that are clinically meaningful by the judgment of the investigator. A 12-lead ECG was performed and all ECG recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed.
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)
Population: All participants who received study drug on Day 1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 3 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 1 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 5 participants |
Secondary
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Low platelet count: \<0.85 x lower limit of normal (LLN) (or if pre-treatment value \<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.
Population: All participants who received study drug on Day 1 and were evaluated for these measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low platelet count | 0 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low leukocytes | 1 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low neutrophils+bands (absolute) | 1 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low lymphocytes (absolute) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low leukocytes | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low neutrophils+bands (absolute) | 2 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low lymphocytes (absolute) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low platelet count | 1 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low neutrophils+bands (absolute) | 1 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low leukocytes | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low lymphocytes (absolute) | 1 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low platelet count | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low lymphocytes (absolute) | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low leukocytes | 1 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low platelet count | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements | Low neutrophils+bands (absolute) | 0 participants |
Secondary
Number of Participants With Serum Chemistry MAs
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify the criteria for MAs in the data presented. High bilirubin (total): \>1.1 x ULN (or if pre-treatment value \>ULN, then \>1.25 x pre-treatment value). High creatinine: \>1.33 x pre-treatment value. Low albumin: \<0.9 x LLN (or if pre-treatment value \<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.
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High creatinine (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High amylase (total) (n = 5, 1, 0, 7) | 0 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High bilirubin (total) (n = 5, 1, 1, 7) | 1 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Serum Chemistry MAs | Low albumin (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High bilirubin (total) (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High amylase (total) (n = 5, 1, 0, 7) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High creatinine (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Serum Chemistry MAs | Low albumin (n = 5, 1, 1, 7) | 1 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High bilirubin (total) (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High amylase (total) (n = 5, 1, 0, 7) | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Serum Chemistry MAs | Low albumin (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Serum Chemistry MAs | High creatinine (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Serum Chemistry MAs | High amylase (total) (n = 5, 1, 0, 7) | 1 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Serum Chemistry MAs | High creatinine (n = 5, 1, 1, 7) | 1 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Serum Chemistry MAs | Low albumin (n = 5, 1, 1, 7) | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Serum Chemistry MAs | High bilirubin (total) (n = 5, 1, 1, 7) | 0 participants |
Secondary
Number of Participants With Urinalysis MAs
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following urinalysis MA definitions specify the criteria for MAs in the data presented. The presence of white blood cells (WBCs) and red blood cells (RBCs) in the urine was graded on a scale: 0 = no cells present (negative); trace =a small number of cells present; then 1+, 2+, 3+ and 4+, denoting increasingly positive urine results (ie, WBCs/RBCs present in the urine). The MA for both WBCs and RBCs was \>= 2+ (or, if pre-treatment value \>=2+, then \>= 4+).
Time frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Population: All participants who received study drug on Day 1 and were evaluated for these measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Urinalysis MAs | White blood cells (WBCs) | 1 participants |
| EFV600mg Participants With Mild Hepatic Impairment | Number of Participants With Urinalysis MAs | Red blood cells (RBCs) | 1 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Urinalysis MAs | Red blood cells (RBCs) | 0 participants |
| EFV600mg Participants With Moderate Hepatic Impairment | Number of Participants With Urinalysis MAs | White blood cells (WBCs) | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Urinalysis MAs | White blood cells (WBCs) | 0 participants |
| EFV600mg Participants With Severe Hepatic Impairment | Number of Participants With Urinalysis MAs | Red blood cells (RBCs) | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Urinalysis MAs | White blood cells (WBCs) | 0 participants |
| EFV600mg Participants With Normal Hepatic Function | Number of Participants With Urinalysis MAs | Red blood cells (RBCs) | 0 participants |