Table 2.
Pharmacokinetic parameters [geometric mean (CV%)] of all analytes for 3 mg BID oral risperidone and 180 mg RBP-7000 Doses 3 (last abdominal injection) and 4 (back of upper arm injection)
| Pharmacokinetic parameter | Na | Risperidone | 9-hydroxy-risperidone | Total active moiety |
|---|---|---|---|---|
| Cavg(ss) (ng/mL) | ||||
| Oral risperidone | 16 | 5.15 (43%) | 38.80 (40%) | 43.73 (35%) |
| Dose 3 RBP-7000 | 16 | 10.20 (65%) | 33.04 (29%) | 44.05 (24%) |
| Dose 4 RBP-7000 | 14 | 11.62 (63%) | 30.72 (31%) | 43.73 (24%) |
| GMR (90% CI)b, Dose 4 versus Dose 3 | – | 1.12 (1.00, 1.25) | 0.94 (0.86, 1.03) | 0.99 (0.92,1.07) |
| GMR (90% CI)b, Dose 3 versus oral | – | 1.98 (1.54, 2.55) | 0.85 (0.75, 0.97) | 1.01 (0.91, 1.12) |
| Cmax(ss) (ng/mL) | ||||
| Oral risperidone | 16 | 14.30 (47%) | 48.70 (42%) | 62.32 (35%) |
| Dose 3 RBP-7000 | 16 | 18.64 (55%) | 56.48 (35%) | 70.60 (31%) |
| Dose 4 RBP-7000 | 15 | 29.82 (65%) | 52.24 (27%) | 77.22 (33%) |
| GMR (90% CI)b, Dose 4 versus Dose 3 | – | 1.62 (1.20, 2.18) | 0.92 (0.80, 1.06) | 1.09 (0.95,1.26) |
| GMR (90% CI)b, Dose 3 versus oral | – | 1.30 (0.97, 1.75) | 1.16 (1.05, 1.28) | 1.13 (1.00, 1.28) |
| Cmin(ss) (ng/mL) | ||||
| Oral risperidone | 16 | 1.13 (70%) | 30.92 (41%) | 31.56 (38%) |
| Dose 3 RBP-7000 | 16 | 4.52 (48%) | 16.95 (42%) | 22.25 (38%) |
| Dose 4 RBP-7000 | 14 | 5.02 (49%) | 14.82 (46%) | 22.06 (36%) |
| GMR (90% CI)b, Dose 4 versus Dose 3 | – | 1.13 (0.95, 1.35) | 0.89 (0.77, 1.02) | 1.00 (0.86,1.17) |
| GMR (90% CI)b, Dose 3 versus oral | – | 4.02 (3.03, 5.33) | 0.55 (0.46, 0.65) | 0.70 (0.62, 0.80) |
| Percent fluctuation (%) | ||||
| Oral risperidone | 16 | 251.7 (32%) | 43.8 (30%) | 67.8 (29%) |
| Dose 3 RBP-7000 | 16 | 135.3 (20%) | 115.3 (56%) | 106.2 (29%) |
| Dose 4 RBP-7000 | 14 | 190.1 (67%) | 116.9 (45%) | 118.4 (34%) |
Percent fluctuation was calculated as (Cmax(ss) – Cmin(ss))/Cavg(ss) × 100. Cavg(ss), average plasma concentration at steady-state; Cmax(ss), maximum plasma concentration at steady-state; Cmin(ss), minimum plasma concentration at steady-state; CI, confidence interval; CV, coefficient of variation; GMR, geometric mean ratio; BID, twice daily
aThe primary pharmacokinetic analysis (comparison of RBP-7000 Dose 3 to oral risperidone) only included participants who received at least 3 doses of RBP-7000 and provided an adequate number of blood samples for the determination of Cavg (ss) for risperidone and total active moiety.
bGMRs and 90% CIs were derived from random effects models, with the logarithm of the pharmacokinetic parameter value as the dependent variable, dose number as the independent variable, and subject as a random effect. A 90% CI lying within the bioequivalence range of 0.80–1.25 indicates bioequivalence; a 90% CI lying outside the bioequivalence range of 0.80–1.25 indicates non-bioequivalence; for any other scenario, no conclusion can be reached.