Table 4.
PK assessments in healthy adults and older subjects in studies B8271001 and B8271004
| Part A: PF-06751979 single-ascending dose in healthy adultsa | ||||||||
| Dose | 3 mg | 12 mg | 40 mg | 160 mg | 200 mg | 400 mg | 540 mg | 200 mg fed |
| N, n | 5, 3 | 6, 5 | 6, 5 | 6, 6 | 6, 6 | 6, 6 | 6, 6 | 6, 6 |
| Cmax, ng/mL | 8.4 (14) | 27.4 (36) | 78.7 (30) | 530.8 (41) | 643.2 (19) | 1436.0 (10) | 1829.0 (19) | 630.2 (9) |
| Tmax, h | 4.03 (4.00–8.00) | 4.11 (2.0–12.00) | 4.08 (2.00–8.05) | 3.03 (1.87–4.08) | 4.00 (2.00–6.07) | 3.02 (2.00–4.00) | 3.01 (2.00–6.02) | 6.00 (4.00–8.00) |
| AUCinf, ng.hr/mL | 289.7 (8) | 1142 (25) | 3121 (25) | 17050 (18) | 22850 (17) | 44980 (17) | 63420 (9) | 23260 (15) |
| t1/2, h | 29.30±0.60 | 32.94±4.92 | 32.12±3.64 | 39.33±8.20 | 35.20±8.97 | 34.70±8.97 | 35.85±8.10 | 33.38±6.25 |
| CL/F, mL/min | 172.3 (8) | 175.0 (25) | 213.4 (25) | 156.3 (18) | 145.8 (17) | 148.3 (17) | 142.0 (9) | 143.3 (15) |
| Vz/F, L | 436.8 (6) | 494.8 (20) | 591.4 (26) | 523.2 (25) | 433.7 (18) | 433.0 (19) | 431.1 (19) | 408.1 (16) |
| Part B: PF-06751979 multiple-ascending dose in healthy adultsa | |||||
| Dose | 5 mg | 15 mg | 50 mg | 125 mg | 275 mg |
| Day 1 | |||||
| N | 8 | 8 | 8 | 12 | 9 |
| Cmax, ng/mL | 10.12 (22) | 28.90 (22) | 120.6 (17) | 442.7 (20) | 983.0 (18) |
| Tmax, h | 3.98 (2.03–12.3) | 4.07 (4.00–7.83) | 2.99 (1.02–4.07) | 4.00 (2.00–6.03) | 4.00 (2.00–4.00) |
| AUCtau, ng.hr/mL | 167.7 (18) | 478.8 (20) | 1739 (14) | 6380 (15) | 13260 (18) |
| Day 7 | |||||
| N | 8 | 8 | 8 | 12 | 9 |
| Cmax, ng/mL | 20.68 (22) | 64.34 (12) | 241.1 (20) | 818.7 (19) | 2000 (14) |
| Tmax, h | 6.02 (3.95–8.05) | 4.02 (2.17–8.03) | 3.83 (1.43–4.07) | 3.00 (2.00–6.00) | 2.00 (2.00–4.00) |
| AUCtau, ng.h/mL | 395.2 (20) | 1149 (12) | 4181 (20) | 13810 (16) | 31210 (14) |
| Day 14 | |||||
| N, n | 8, 8 | 8, 8 | 8, 8 | 12, 12 | 8, 8 |
| Cmax, ng/mL | 22.41 (23) | 64.63 (14) | 245.7 (21) | 837.6 (16) | 1869 (14) |
| Tmax, h | 4.01 (3.98–8.02) | 4.05 (4.02–7.87) | 3.00 (0.88–8.08) | 4.00 (2.00–12.00) | 4.00 (2.00–4.00) |
| t1/2, h | 37.15±5.20 | 30.65±3.19 | 37.36±5.91 | 30.73±5.75 | 37.79±7.73 |
| CL/F, mL/min | 197.1 (20) | 216.9 (12) | 196.9 (24) | 149.0 (14) | 155.3 (13) |
| Vz/F, L | 628.7 (18) | 573.2 (12) | 629.0 (27) | 390.5 (23) | 498.3 (27) |
| AUCtau, ng.hr/mL | 422.2 (20) | 1152 (13) | 4236 (24) | 13990 (14) | 29470 (12) |
| Cmin, ng/mL | 12.55 (22) | 32.75 (14) | 120.4 (25) | 390.3 (18) | 868.5 (15) |
| Rac | 2.52 (12) | 2.41 (14) | 2.43 (15) | 2.19 (11) | 2.27 (11) |
| Part C: PF-06751979 multiple doses in healthy older subjectsa | ||
| Dose | 50 mg | 125 mg |
| Day 1 | ||
| N | 10 | 8 |
| Cmax, ng/mL | 102.9 (25) | 377.1 (30) |
| Tmax, h | 4.00 (2.02–7.98) | 4.00 (2.00–4.03) |
| AUCtau, ng.hr/mL | 1621 (22) | 5238 (24) |
| Day 14 | ||
| N, n | 8, 8 | 8, 8 |
| Cmax, ng/mL | 256.4 (23) | 879.4 (28) |
| Tmax, h | 4.00 (2.00–4.20) | 4.00 (2.00–4.03) |
| t1/2, h | 39.95±3.18 | 40.76±3.90 |
| CL/F, mL/min | 184.9 (20) | 141.4 (23) |
| Vz/F, L | 637.4 (23) | 496.1 (30) |
| AUCtau, ng.h/mL | 4505 (20) | 14750 (23) |
| Cmin, ng/mL | 135.8 (18) | 429.9 (23) |
aGeometric mean (% CV) for all PK parameters except: median (range) for Tmax; arithmetic mean±SD for t1/2. AUCinf, area under the plasma concentration–time curve from time 0 to infinity; AUCtau, area under the plasma concentration–time curve from over the dosing interval tau (τ) where τ equals 24 h for QD dosing; CL/F, apparent clearance; Cmin, minimum observed concentration during the dosing interval; Cmax,maximum observed concentration; CV, coefficient of variation; N, number of subjects in the treatment group and contributing to the summary statistics for the specified day; n, number of subjects for t1/2 and Vz/F; PK, pharmacokinetic; Rac, observed accumulation ratio; t1/2, terminal half-life; SD, standard deviation; Tmax, time to reach maximum concentration; Vz/F, apparent volume of distribution.