Trial Outcomes & Findings for Study of Pirtobrutinib (LOXO-305) in Participants With Impaired Liver Function and Healthy Participants (NCT NCT06190691)
NCT ID: NCT06190691
Last Updated: 2025-01-09
Results Overview
PK: Cmax of pirtobrutinib
COMPLETED
PHASE1
36 participants
Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)
2025-01-09
Participant Flow
Participant milestones
| Measure |
Pirtobrutinib (Normal Hepatic Function)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
14
|
8
|
8
|
6
|
|
Overall Study
Received Dose of Pirtobrutinib
|
14
|
8
|
8
|
6
|
|
Overall Study
COMPLETED
|
12
|
8
|
8
|
6
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Pirtobrutinib (Normal Hepatic Function)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
0
|
0
|
Baseline Characteristics
Study of Pirtobrutinib (LOXO-305) in Participants With Impaired Liver Function and Healthy Participants
Baseline characteristics by cohort
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.4 years
STANDARD_DEVIATION 8.22 • n=5 Participants
|
56.8 years
STANDARD_DEVIATION 4.560 • n=7 Participants
|
56.3 years
STANDARD_DEVIATION 3.920 • n=5 Participants
|
52.3 years
STANDARD_DEVIATION 9.350 • n=4 Participants
|
55 years
STANDARD_DEVIATION 6.880 • n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
17 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: Cmax of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Pirtobrutinib
|
4240 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 32.4
|
4410 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 22.7
|
4140 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 20.8
|
3270 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 22.8
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: Tmax of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
|
2.50 hours
Interval 1.0 to 8.0
|
2.25 hours
Interval 1.0 to 6.0
|
2.25 hours
Interval 1.0 to 3.0
|
2.78 hours
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: AUC0-t of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
|
96800 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 21.2
|
89900 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 43
|
84600 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.7
|
71500 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 14.8
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: AUC0-inf of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib
|
98000 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 20.7
|
90900 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 42.7
|
85700 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.1
|
72200 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 14.6
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: %AUCextrap of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib
|
0.978 percentage of AUCextrap
Geometric Coefficient of Variation 67.3
|
1.13 percentage of AUCextrap
Geometric Coefficient of Variation 34.4
|
1.14 percentage of AUCextrap
Geometric Coefficient of Variation 54.7
|
0.921 percentage of AUCextrap
Geometric Coefficient of Variation 50.4
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: t½ of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib
|
21.2 hours
Geometric Coefficient of Variation 20.9
|
19.8 hours
Geometric Coefficient of Variation 27.7
|
18 hours
Geometric Coefficient of Variation 16.3
|
15.5 hours
Geometric Coefficient of Variation 26.6
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: CL/F of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
|
2.04 liter per hour (L/h)
Geometric Coefficient of Variation 20.7
|
2.20 liter per hour (L/h)
Geometric Coefficient of Variation 42.7
|
2.33 liter per hour (L/h)
Geometric Coefficient of Variation 31.1
|
2.77 liter per hour (L/h)
Geometric Coefficient of Variation 14.6
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: Vz/F of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib
|
62.4 Liter (L)
Geometric Coefficient of Variation 29.5
|
62.9 Liter (L)
Geometric Coefficient of Variation 45.1
|
60.6 Liter (L)
Geometric Coefficient of Variation 30.1
|
61.8 Liter (L)
Geometric Coefficient of Variation 30.5
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
MRT is the average time a drug molecule stays in the body, calculated from the AUC0-inf.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Mean Residence Time (MRT) of Pirtobrutinib
|
28.8 hours
Geometric Coefficient of Variation 17.6
|
27.7 hours
Geometric Coefficient of Variation 26.3
|
25 hours
Geometric Coefficient of Variation 14
|
24 hours
Geometric Coefficient of Variation 26.2
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Unbound Cmax (Cmax,u) of Pirtobrutinib
|
107 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 31.2
|
133 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 16.3
|
118 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 26.5
|
111 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 27.5
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib
|
2440 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 22.8
|
2710 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 32.3
|
2410 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.6
|
2410 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.5
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib
|
2470 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 22.6
|
2740 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 32.1
|
2440 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.1
|
2440 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.5
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Unbound CL/F (CL/F,u) of Pirtobrutinib
|
80.9 liter per hour (L/h)
Geometric Coefficient of Variation 22.6
|
73 liter per hour (L/h)
Geometric Coefficient of Variation 32.1
|
81.9 liter per hour (L/h)
Geometric Coefficient of Variation 39.1
|
82 liter per hour (L/h)
Geometric Coefficient of Variation 28.5
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib
|
2470 Liter (L)
Geometric Coefficient of Variation 26
|
2090 Liter (L)
Geometric Coefficient of Variation 34
|
2130 Liter (L)
Geometric Coefficient of Variation 33.1
|
1830 Liter (L)
Geometric Coefficient of Variation 36.3
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: λZ of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 12
|
0.0308 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 13
|
0.0399 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 1
|
0.0334 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 2
|
0.0323 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 3
|
0.0418 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 4
|
0.0287 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 5
|
0.0231 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 6
|
0.0319 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 7
|
0.0420 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 8
|
0.0262 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 9
|
0.0292 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 10
|
0.0291 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 11
|
0.0299 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)
Subject 14
|
0.0491 1/hour (1/h)
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: λZ of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 15
|
0.0270 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 16
|
0.0448 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 17
|
0.0453 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 18
|
0.0336 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 19
|
0.0234 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 20
|
0.0273 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 21
|
0.0432 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)
Subject 22
|
0.0440 1/hour (1/h)
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: λZ of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=8 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 23
|
0.0377 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 24
|
0.0387 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 25
|
0.0364 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 26
|
0.0430 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 27
|
0.0395 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 28
|
0.0467 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 29
|
0.0419 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)
Subject 30
|
0.0272 1/hour (1/h)
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose)Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.
PK: λZ of pirtobrutinib
Outcome measures
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=6 Participants
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 31
|
0.0401 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 32
|
0.0526 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 33
|
0.0279 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 34
|
0.0522 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 35
|
0.0465 1/hour (1/h)
|
—
|
—
|
—
|
|
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)
Subject 36
|
0.0567 1/hour (1/h)
|
—
|
—
|
—
|
Adverse Events
Pirtobrutinib (Normal Hepatic Function)
Pirtobrutinib (Mild Hepatic Impairment)
Pirtobrutinib (Moderate Hepatic Impairment)
Pirtobrutinib (Severe Hepatic Impairment)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pirtobrutinib (Normal Hepatic Function)
n=14 participants at risk
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Mild Hepatic Impairment)
n=8 participants at risk
Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
|
Pirtobrutinib (Moderate Hepatic Impairment)
n=8 participants at risk
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
Pirtobrutinib (Severe Hepatic Impairment)
n=6 participants at risk
Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/14 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
12.5%
1/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
16.7%
1/6 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
1/14 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/6 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
|
Investigations
SARS-CoV-2 test positive
|
14.3%
2/14 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/6 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
|
Nervous system disorders
Headache
|
0.00%
0/14 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
12.5%
1/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/8 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
0.00%
0/6 • Baseline to Follow-up (Up To Day 17)
All participants who received a dose of Pirtobrutinib.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60