Why carry out this study? |
Deucravacitinib is a novel tyrosine kinase 2 inhibitor approved for the treatment of plaque psoriasis. |
There may be racial or ethnic effects on drug pharmacokinetics and metabolism. |
This study evaluated the pharmacokinetics and safety of deucravacitinib in healthy Chinese subjects to determine if there were racial and ethnic disparities. |
What was learned from the study? |
Deucravacitinib was safe and well tolerated, and exhibited similar pharmacokinetics and dose effects in healthy Chinese subjects as reported for the general population in previous studies. |
Chinese ethnicity has minimal effect on deucravacitinib pharmacokinetics. |
Introduction
Methods
Study Design
Participants
Pharmacokinetic Sampling and Bioanalytical Methodology
Pharmacokinetic Analyses
Safety Analyses
Statistical Analyses
Results
Baseline Subject Demographics and Clinical Characteristics
Category or statistic | Safety set | Pharmacokinetic set | |||
---|---|---|---|---|---|
Placebo (n = 8) | Deucravacitinib 6 mg (n = 16) | Deucravacitinib 12 mg (n = 16) | Overall (N = 40) | Overall (N = 32) | |
Sex, n (%) | |||||
Male | 4 (50) | 7 (43.8) | 10 (62.5) | 21 (52.5) | 17 (53.1) |
Female | 4 (50) | 9 (56.3) | 6 (37.5) | 19 (47.5) | 15 (46.9) |
Age, mean (SD), years | 31.3 (6.09) | 31.4 (7.21) | 32.8 (7.71) | 32.0 (7.07) | 32.1 (7.38) |
Height, mean (SD), cm | 167.1 (7.94) | 162.4 (7.14) | 164.8 (9.71) | 164.3 (8.39) | 163.6 (8.48) |
Weight, mean (SD), kg | 57.80 (4.396) | 59.35 (4.381) | 59.87 (6.495) | 59.25 (5.260) | 59.61 (5.456) |
Body mass index, mean (SD), kg/m2 | 20.75 (1.666) | 22.54 (1.468) | 22.02 (1.053) | 21.98 (1.482) | 22.28 (1.285) |
Pharmacokinetics of Deucravacitinib and Metabolites
Parameter | Deucravacitinib 6 mg Once daily (n = 16) | Deucravacitinib 12 mg Once daily (n = 16) | Ratio of deucravacitinib 12 mg:6 mg |
---|---|---|---|
Cmax, geometric mean (%CV), ng/mL | 66.8 (15.4) | 155.0 (19.1) | 2.3:1 |
tmax, median (min, max), h | 2.25 (1.50, 3.00) | 1.50 (0.50, 2.50) | 0.7:1 |
t1/2, mean (SD), h | 12.5 (4.53) | 14.8 (6.55) | 1.2:1 |
AUC0–t, geometric mean (%CV), h·ng/mL | 600 (17.7) | 1250 (23.9) | 2.1:1 |
AUC0–∞, geometric mean (%CV), h·ng/mL | 613 (17.6) | 1271 (23.6) | 2.1:1 |
CLT/F, geometric mean (%CV), L/h | 9.78 (18.1) | 9.44 (21.7) | 1.0:1 |
URt, mean (SD), mg | 0.786 (0.188) | 1.42 (0.272) | 1.8:1 |
pURt, mean (SD), % | 13.1 (3.14) | 11.8 (2.27) | 0.9:1 |
CLR, geometric mean (%CV), L/h | 1.25 (18.3) | 1.09 (19.5) | 0.9:1 |
Parameter | Day 5 (first day of once-daily dosing) | Day 19 (last day of once-daily dosing) | ||||
---|---|---|---|---|---|---|
Deucravacitinib 6 mg (n = 15) | Deucravacitinib 12 mg (n = 16) | Ratio of deucravacitinib 12 mg:6 mg | Deucravacitinib 6 mg (n = 15) | Deucravacitinib 12 mg (n = 16) | Ratio of deucravacitinib 12 mg:6 mg | |
Cmax, geometric mean (%CV), ng/mL | 70.7 (13.0) | 142.0 (16.6) | 2.0:1 | 87.1 (14.1) | 177.0 (20.6) | 2.0:1 |
tmax, median (min, max), h | 2.00 (1.00, 3.00) | 2.02 (1.00, 4.00) | 1.0:1 | 2.00 (1.00, 3.00) | 2.00 (1.00, 4.00) | 1.0:1 |
AUCtau, geometric mean (%CV), h·ng/mL | 576 (16.1) | 1118 (18.8) | 1.9:1 | 775 (19.0) | 1559 (22.7) | 2.0:1 |
AI-AUCtau, geometric mean (%CV) | – (–) | – (–) | NA | 1.34 (8.40) | 1.39 (10.9) | 1.0:1 |
Parameter | BMT-158170 | BMT-153261 | ||
---|---|---|---|---|
Deucravacitinib 6 mg Once daily (n = 16) | Deucravacitinib 12 mg Once daily (n = 16) | Deucravacitinib 6 mg Once daily (n = 16) | Deucravacitinib 12 mg Once daily (n = 16) | |
Cmax, geometric mean (%CV), ng/mL | 17.1 (27.5) | 34.6 (18.1) | 6.92 (2.40) | 17.1 (5.90) |
tmax, median (min, max), h | 2.50 (1.00, 4.00) | 2.25 (1.00, 4.00) | 6.00 (3.00, 10.00) | 4.00 (4.00, 6.00) |
t1/2, h, mean (SD) | 11.4 (4.63) | 15.8 (9.08) | 13.5 (2.46) | 16.3 (5.75) |
AUC0–∞, geometric mean (%CV), h·ng/mL | 210 (34.7) | 419 (28.1) | 163 (45.4) | 360 (82.3) |
MR Cmax, geometric mean (%CV) | 0.305 (22.0) | 0.267 (19.8) | 0.102 (37.4) | 0.109 (35.7) |
MR AUC0–∞, geometric mean (%CV) | 0.409 (25.9) | 0.393 (22.0) | 0.266 (34.6) | 0.286 (32.6) |
Parameter | Day 5 (first day of once-daily dosing) | Day 19 (last day of once-daily dosing) | ||||||
---|---|---|---|---|---|---|---|---|
Deucravacitinib 6 mg | Deucravacitinib 12 mg | Deucravacitinib 6 mg | Deucravacitinib 12 mg | |||||
BMT-158170 (n = 15) | BMT-153261 (n = 15) | BMT-158170 (n = 16) | BMT-153261 (n = 16) | BMT-158170 (n = 15) | BMT-153261 (n = 15) | BMT-158170 (n = 16) | BMT-153261 (n = 16) | |
Cmax, geometric mean (%CV), ng/mL | 18.9 (24.8) | 6.73 (26.5) | 34.1 (20.3) | 16.1 (36.5) | 25.5 (27.1) | 9.62 (24.0) | 51.4 (24.9) | 20.6 (27.0) |
tmax, median (min, max), h | 3.00 (2.00, 4.00) | 4.00 (4.00, 8.00) | 3.00 (2.00, 4.00) | 4.00 (4.00, 8.00) | 3.00 (2.00, 4.00) | 4.00 (3.00, 4.00) | 2.00 (2.00, 6.00) | 4.00 (3.00, 6.00) |
AUCtau, geometric mean (%CV), h·ng/mL | 194 (31.1) | 106 (21.9) | 345 (28.7) | 236 (67.1) | 298 (35.7) | 159 (38.2) | 612 (39.0) | 344 (89.9) |
Safety
Adverse event, n (%) | Deucravacitinib, single dose | Deucravacitinib, multiple doses | ||||
---|---|---|---|---|---|---|
Placebo (n = 8) | 6 mg (n = 16) | 12 mg (n = 16) | Placebo (n = 8) | 6 mg (n = 15) | 12 mg (n = 16) | |
TEAE | 1 (12.5) | 1 (6.3) | 3 (18.8) | 3 (37.5) | 5 (33.3) | 13 (81.3) |
Severe TEAE | 0 | 0 | 0 | 0 | 1 (6.7) | 1 (6.3) |
Treatment-related TEAE | 0 | 0 | 3 (18.8) | 2 (25.0) | 5 (33.3) | 12 (75.0) |
Serious TEAE | 0 | 1 (6.3) | 0 | 0 | 0 | 0 |
Treatment-related serious TEAE | 0 | 0 | 0 | 0 | 0 | 0 |
TEAE leading to discontinuation | 0 | 0 | 0 | 0 | 0 | 0 |
Treatment-related TEAE leading to discontinuation | 0 | 0 | 0 | 0 | 0 | 0 |