Trial Outcomes & Findings for Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment (NCT NCT00162097)
NCT ID: NCT00162097
Last Updated: 2010-09-14
Results Overview
Cmax was obtained directly from the concentration-time data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
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.
Results posted on
2010-09-14
Participant Flow
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).
Participant milestones
| Measure |
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
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
2
|
1
|
7
|
|
Overall Study
COMPLETED
|
6
|
2
|
1
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
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
|
|---|---|---|---|---|
|
Overall Study
Participant no longer met study criteria
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
Baseline characteristics by cohort
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
50 years
STANDARD_DEVIATION 11 • n=5 Participants
|
51 years
STANDARD_DEVIATION 1 • n=7 Participants
|
47 years
n=5 Participants
|
49 years
STANDARD_DEVIATION 4 • n=4 Participants
|
49 years
STANDARD_DEVIATION 7 • n=21 Participants
|
|
Age, Customized
< 65 years
|
5 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
7 participants
n=4 Participants
|
15 participants
n=21 Participants
|
|
Age, Customized
>= 65 years
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
American Indian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
5 participants
n=4 Participants
|
9 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
5 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Body mass index (BMI) Continuous
|
26.3 kg/m^2
STANDARD_DEVIATION 3.7 • n=5 Participants
|
24.6 kg/m^2
STANDARD_DEVIATION 0.1 • n=7 Participants
|
24.0 kg/m^2
n=5 Participants
|
22.8 kg/m^2
STANDARD_DEVIATION 2.2 • n=4 Participants
|
24.4 kg/m^2
STANDARD_DEVIATION 3.0 • n=21 Participants
|
|
Height Continuous
|
165.5 cm
STANDARD_DEVIATION 11.9 • n=5 Participants
|
173.4 cm
STANDARD_DEVIATION 3.7 • n=7 Participants
|
160.0 cm
n=5 Participants
|
175.6 cm
STANDARD_DEVIATION 7.2 • n=4 Participants
|
170.6 cm
STANDARD_DEVIATION 10.0 • n=21 Participants
|
|
Weight, Continuous
|
71.5 kilogram
STANDARD_DEVIATION 7.2 • n=5 Participants
|
73.9 kilogram
STANDARD_DEVIATION 2.9 • n=7 Participants
|
61.5 kilogram
n=5 Participants
|
70.4 kilogram
STANDARD_DEVIATION 9.6 • n=4 Participants
|
70.7 kilogram
STANDARD_DEVIATION 7.9 • n=21 Participants
|
PRIMARY outcome
Timeframe: 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.
Cmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=6 Participants
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
|
|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
5.303 micrograms (mcg)/mL
Interval 2.73 to 16.0
|
8.964 micrograms (mcg)/mL
Interval 4.9 to 16.4
|
6.750 micrograms (mcg)/mL
Interval 6.75 to 6.75
|
6.515 micrograms (mcg)/mL
Interval 2.68 to 25.3
|
—
|
PRIMARY outcome
Timeframe: 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.
Cmin was obtained directly from the concentration-time data.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=6 Participants
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
|
|---|---|---|---|---|---|
|
Minimum Plasma Concentration (Cmin)
|
2.599 mcg/mL
Interval 0.688 to 11.5
|
4.885 mcg/mL
Interval 1.85 to 12.9
|
3.780 mcg/mL
Interval 3.78 to 3.78
|
2.405 mcg/mL
Interval 0.611 to 17.9
|
—
|
PRIMARY outcome
Timeframe: 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.
The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=1 Participants
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
n=1 Participants
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
n=6 Participants
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
|
|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])
|
83.422 mcg*h/mL
Interval 29.84 to 323.06
|
75.425 mcg*h/mL
Interval 75.425 to 75.425
|
101.912 mcg*h/mL
Interval 101.912 to 101.912
|
93.516 mcg*h/mL
Interval 36.51 to 486.43
|
—
|
PRIMARY outcome
Timeframe: 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.
Tmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=6 Participants
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
|
|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
|
1.765 hours
Interval 0.98 to 6.03
|
4.500 hours
Interval 3.0 to 6.0
|
1.000 hours
Interval 1.0 to 1.0
|
3.500 hours
Interval 2.0 to 6.0
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
n=5 Participants
Participants were enrolled in the study and discontinued prior to study drug administration
|
|---|---|---|---|---|---|
|
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
Other Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants Who Experienced AEs
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=5 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Low neutrophils+bands (absolute)
|
1 participants
|
2 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Low platelet count
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Low leukocytes
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Low lymphocytes (absolute)
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Serum Chemistry MAs
High bilirubin (total) (n = 5, 1, 1, 7)
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Serum Chemistry MAs
High creatinine (n = 5, 1, 1, 7)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Serum Chemistry MAs
Low albumin (n = 5, 1, 1, 7)
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Serum Chemistry MAs
High amylase (total) (n = 5, 1, 0, 7)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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+).
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=5 Participants
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
n=1 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Urinalysis MAs
Red blood cells (RBCs)
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Urinalysis MAs
White blood cells (WBCs)
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
|
3 participants
|
1 participants
|
0 participants
|
5 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Clinically Meaningful Vital Signs Measures
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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
Outcome measures
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 Participants
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
n=2 Participants
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
n=1 Participants
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
n=7 Participants
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
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)
|
5 participants
|
2 participants
|
1 participants
|
5 participants
|
—
|
Adverse Events
EFV600mg Participants With Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
EFV600mg Participants With Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
EFV600mg Participants With Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
EFV600mg Participants With Normal Hepatic Function
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Not Dosed
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 participants at risk
|
EFV600mg Participants With Moderate Hepatic Impairment
n=2 participants at risk
|
EFV600mg Participants With Severe Hepatic Impairment
n=1 participants at risk
|
EFV600mg Participants With Normal Hepatic Function
n=7 participants at risk
|
Not Dosed
n=5 participants at risk
|
|---|---|---|---|---|---|
|
Infections and infestations
OESOPHAGEAL CANDIDIASIS
|
0.00%
0/6
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/2
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/1
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/7
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
20.0%
1/5
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
|
Infections and infestations
AIDS RELATED COMPLICATION
|
0.00%
0/6
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/2
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/1
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/7
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
20.0%
1/5
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/6
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/2
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/1
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/7
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
20.0%
1/5
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
Other adverse events
| Measure |
EFV600mg Participants With Mild Hepatic Impairment
n=6 participants at risk
|
EFV600mg Participants With Moderate Hepatic Impairment
n=2 participants at risk
|
EFV600mg Participants With Severe Hepatic Impairment
n=1 participants at risk
|
EFV600mg Participants With Normal Hepatic Function
n=7 participants at risk
|
Not Dosed
n=5 participants at risk
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
16.7%
1/6
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/2
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/1
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/7
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
0.00%
0/5
One participant enrolled twice in the study in EFV600mg participants with normal hepatic function group and is hence counted twice in this group.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER