TABLE 6.
Summary of select pharmacokinetic parameters in part C a of the study (pharmacokinetic population b )
| PK parameter | Day | n/N | GSK3358699 | GSK3206944 (metabolite) | ||
|---|---|---|---|---|---|---|
| Geometric mean (%CVb) | 95% CI | Geometric mean (%CVb) | 95% CI | |||
| AUC(0‐t), h*ng/mL | 1 | 14/14 | 9.5 (43.4) | (7.4, 12.0) | 125.2 (42.3) | (99.0, 158.2) |
| 14 | 2/14 | 11.0 (−) | … | 108.7 (−) | … | |
| AUC(0‐∞), h*ng/mL | 1 | 7/14 | 9.8 (35.1) | (7.2, 13.4) | 128.4 (41.6) | (102.0, 161.8) |
| 14 | 0/14 | … | … | … | … | |
| AUC(0‐24), h*ng/mL | 1 | 7/14 | 9.8 (35.1) | (7.1, 13.4) | 125.4 (42.3) | (99.2, 158.4) |
| 14 | 1/14 | 8.0 (−) | … | 105.6 (−) | … | |
| AUC(0‐tau), h*ng/mL | 1 | 7/14 | 9.8 (35.1) | (7.1, 13.4) | 125.4 (42.3) | (99.2, 158.4) |
| 14 | 1/14 | 8.0 (−) | … | 105.6 (−) | … | |
| C max, ng/mL | 1 | 14/14 | 6.1 (54.0) | (4.6, 8.2) | 23.8 (44.2) | (18.7, 30.4) |
| 14 | 2/14 | 5.9 (−) | … | 15.3 (−) | … | |
| T max, h* | 1 | 14/14 | 0.5 (0.3, 2.0) | … | 2.0 (1.0, 2.0) | … |
| 14 | 2/14 | 0.5 (0.5, 0.6) | … | 1.0 (1.0, 1.0) | … | |
| t 1/2 (terminal), h* | 1 | 7/14 | 2.5 (1.4, 3.0) | … | 5.0 (3.3, 5.6) | … |
| 14 | 1/14 | 1.6 (−) | … | 6.2 (5.5, 6.8) | … | |
| t 1/2 (initial), h* | 1 | 13/14 | 1.0 (0.6, 1.5) | … | 2.4 (1.7, 4.0) | … |
| 14 | 2/14 | 0.8 (0.7, 0.8) | … | 3.7 (2.8, 4.5) | … | |
| R 0 | 14 | 1/14 | 0.6 (−) | … | 1.3 (−) | … |
| R S | 14 | 1/14 | 0.6 (−) | … | 1.2 (−) | … |
AUC(0‐t), area under the concentration‐time curve from time zero to the time of the last quantifiable concentration; AUC(0‐∞), area under the concentration‐time curve extrapolated to infinity; AUC(0‐24), area under the concentration‐time curve from time zero to 24 hours post‐dose; AUC(0‐tau), area under the concentration‐time curve from time zero to the end of the dosing period; CI, confidence interval; C max, maximum observed concentration; CVb, coefficient of variation; N, total number of participants; n, number of participants with nonmissing observations. PK, pharmacokinetic; R 0, accumulation between one single dose (day 1) and repeat dose (day 14); R S, steady state ratio; T max, time to reach C max; t 1/2 (terminal), apparent terminal half‐life; t 1/2 (initial), actual initial half‐life.
In part C, participants received 10 mg of GSK3358699 or placebo daily for up to 14 days.
The pharmacokinetic population included all participants who received an active dose of the study drug and for whom pharmacokinetic samples were obtained and analysed.
N, total number of participants; n, number of participants with nonmissing observations.