Table 1.
Studies included in the population pharmacokinetic analysis of cariprazine, DCAR, and DDCAR
| Study number [citation] | Development phase (design) | Study population | Planned number of patients receiving cariprazine | Planned cariprazine doses at time of PK sample collection, mg | Planned duration of active treatment, days |
|---|---|---|---|---|---|
| RGH-MD-01 [25]a | 1 | Schizophrenia | 48 (6 per cohort) | 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 5.5, 7, 7.5, 9.5, 12.5 | 22 (30 for Cohort G) |
| RGH-MD-02a | 1b | Schizophrenia | 50 | 1.5, 12, 18 | 35 |
| RGH-MD-03 [13]b | 2 (RDBPC) | Schizophrenia | 250 (125 per group) | 4.5, 12 | 42 |
| RGH-MD-04 [4]b | 3 (RDBPC) | Schizophrenia | 300 (150 per group) | 3, 6 | 42 |
| RGH-MD-05 [3]b | 3 (RDBPC) | Schizophrenia | 300 (150 per group) | 4.5, 6, 7.5, 9 | 42 |
| RGH-MD-11 [14] b,c | 3 (open-label) | Schizophrenia | 600 | 3, 6, 9 | 336 |
| RGH-MD-16 [5]b | 2b (RDBPC) | Schizophrenia | 405 (135 per group) | 1.5, 3, 4.5 | 42 |
| RGH-MD-17 [15]b,c | 2b (open-label) | Schizophrenia | 250 | 1.5, 3, 4.5 | 336 |
| RGH-MD-18a | 1b | Schizophrenia | 24 (6 per cohort) | 1.5, 3, 6, 9, 12, 15, 18, 21 | 28 |
| RGH-MD-32 [7]b | 3 (RDBPC) | Bipolar mania | 160 | 3, 6, 9, 12 | 21 |
| RGH-MD-33 [8]b | 3 (RDBPC) | Bipolar mania | 330 (165 per group) | 3, 4.5, 6, 9, 12 | 21 |
| RGH-MD-36 [16]b | 3 (open-label) | Bipolar mania | 400 | 1.5, 3, 6, 9 | 112 |
| A002-A11 [11]a,d | 2/3 (open-label) | Schizophrenia | 30 | 3, 6, 9 | 84 |
DCAR desmethyl-cariprazine, DDCAR didesmethyl-cariprazine, PK pharmacokinetic, RDBPC randomized, double-blind, placebo-controlled trial
aSerial sampling studies: serial sampling following the first dose was done in four studies, three of which included sampling up to 24 h (RGH-MD-01, RGH-MD-02, and RGH-MD-18) and one that included sampling up to 8 h (A002-A11). Serial sampling was also collected after the last dose in all four studies. For RGH-MD-01, serial sampling over a 168-h period was also done after the 22nd or 30th dose (12.5 mg); for RGH-MD-02, serial sampling over a 24-h period after the 29th dose (18 mg); for RGH-MD-18, serial sampling over a 168 to 192-h period was also done after the 28th dose (doses > 15 mg were excluded). For A002-A11, serial sampling over a 4032-h period (168 days) was also done after the 84th dose. In addition, at least one additional 24-h sampling profile was collected on an intervening dose day. Sparse samples were also collected at a variety of days between the serial samples
bSparse sampling studies: sparse sampling was done at various times across the duration of the studies. The first sample was collected on Day 5 (RGH-MD-32 and RGH-MD-33), Day 7 (RGH-MD-11, RGH-MD-17, and RGH-MD-36), or Day 14 (RGH-MD-03, RGH-MD-04, RGH-MD-05, RGH-MD-16). Sampling following the final dose occurred in all of the studies: a sample up to 24 h postdose, at 336–360 h, and 672–696 h (RGH-MD-03, RGH-MD-11, and RGH-MD-17), a sample up to 24 h postdose and at 336–360 h post dose (RGH-MD-04, RGH-MD-05, RGH-MD-16), and up to 24 h postdose and at 168–192 h (RGH-MD-32, RGH-MD-33, and RGH-MD-36)
cStudies RGH-MD-11 and RGH-MD-17 were not included in the development of the models. The final models were applied to these studies to evaluate the ability of the models to predict into longer-term trials
dThe data for this study were only available for the updated (final) model. Because the study included a serial PK sampling design, it will be treated as a Phase 1 study for the purposes of the PK modeling