Table 1.
Summary of L‐PZQ pharmacokinetic parameters (EMR 200585‐001 and EMR 200661‐001; PK populations)
| Study EMR 200585‐001 | Study EMR 200661‐001 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L‐PZQ | A | B | C1 | C2 | D1 | D2 | A | B | C1 | C2 | D | E |
| Dose mg/kg | 40 | 40 | 20 | 60 | 40 | 40 | 20 | 40 | 10 | 30 | 40 | 40 |
| IMP | Rac‐ODT | Cys | Rac‐ODT | Rac‐ODT | Rac‐ODT | Cys | L‐ODT | Cys | L‐ODT | L‐ODT | L‐ODT | L‐ODT |
| Condition | Fed | Fed | Fed | Fed | Fasted | Crushed,fed | Fed | Fed | Fed | Fed | Fasted | Dispersed in mouth, fed |
| N | 30 | 30 | 14/15 | 15 | 14 | 14/15 | 36 | 36 | 17/18 | 17 | 35 | 36 |
| Cmax (ng/mL) | 881.3 | 762.6 | 154.6 | 1,548 | 189.3 | 446.3 | 378.8 | 727.3 | 89.9 | 1,051.8 | 131.1 | 471.2 |
| (57.2) | (59.5) | (80.4) | (32.6) | (104.0) | (87.6) | (114.1) | (63.3) | (92.2) | (83.6) | (110.6) | (99.5) | |
| 245–2,860 | 218–2,010 | 41.6–542 | 1,020–2,560 | 50.4–1,030 | 65.8–1,150 | 68.4–2,038.1 | 222.4–2,249.4 | 28.8–388.3 | 307.4–3,869.1 | 14.9–648.6 | 71.3–1,694.0 | |
| Tmax (h) | 3.00 | 1.50 | 4.00 | 3.00 | 4.25 | 2.50 | 2.50 | 2.50 | 2.25 | 3.00 | 2.00 | 4.00 |
| 1.00–4.50 | 1.00–4.50 | 1.50–5.00 | 0.50–4.50 | 0.50–4.50 | 0.50–8.00 | 0.50–4.50 | 1.00–4.50 | 1.00–4.50 | 1.00–4.50 | 0.50–4.50 | 0.50–5.00 | |
| AUC0–∞ (h*ng/mL) | 1,969.6 | 2,047.9 | 345.4 | 4,871.3 | 924.9 | 1,537.7 | 825.2 | 2,066.0 | 216.7 | 2,324.9 | 506.2 | 954.5 |
| (47.2) | (60.2) | (69.5) | (42.2) | (67.7) | (70.6) | (101.0) | (64.7) | (102.8) | (76.4) | (100.0) | (96.4) | |
| 561–3,710 | 488–4795 | 129–1,017 | 1,994–8,639 | 326–2,790 | 678–5,294 | 222–4,015 | 665–6,466 | 73–1,147 | 880–10,054 | 59–2,049 | 152–4,532 | |
| t1/2 (h) | 3.305 | 3.830 | 1.916 | 4.202 | 4.168 | 3.072 | 2.777 | 3.827 | 1.604 | 3.361 | 2.837 | 2.625 |
| (49.1) | (46.8) | (72.2) | (37.8) | (34.9) | (43.5) | (53.9) | (46.3) | (88.6) | (31.9) | (62.3) | (65.2) | |
| 1.41–10.62 | 1.68–14.56 | 0.83–7.23 | 2.27–8.17 | 2.25–7.51 | 1.69–7.25 | 1.01–6.49 | 1.44–10.1 | 0.623–7.58 | 1.82–5.46 | 0.869–24.9 | 0.452–6.65 | |
| CL/f (L/h) | 716.8 | 691.3 | 2,028.4 | 438.5 | 1,466.9 | 971.1 | 1665 | 667.3 | 3,091 | 923.5 | 2,729 | 1,440 |
| (45.0) | (57.9) | (60) | (45.8) | (60.6) | (69.5) | (94.3) | (60.1) | (92.9) | (71.4) | (95.4) | (89.3) | |
| 332–2,673 | 248–2,244 | 685–4,727 | 213–1,195 | 590–3,374 | 261–2,263 | 419–7,100 | 194–1,900 | 770–8,940 | 254–2,760 | 826–29,200 | 255–8,530 | |
AUC0–∞, area under the plasma concentration‐time curve from zero to infinity; CL/f, apparent clearance; Cmax, maximum plasma concentration; Cys, Cysticide; EMR, electronic medical record; L‐PZQ, levo‐praziquantel; N, number of subjects included in the analysis; ODT, orally dispersible tablet; PK, pharmacokinetic; rac‐PZQ, racemate praziquantel; t1/2, terminal half‐life; Tmax, time to maximum concentration.
The table presents L‐PZQ PK parameters by geometric mean, GeoCV%, and range (minimum‐maximum); for Tmax median and range are presented. Dose‐dependent parameters are adjusted to the planned dose.
For study EMR 200585–001: A = ODT rac‐PZQ 40 mg/kg dispersed in water, fed; B = Cysticide 40 mg/kg given with water, fed; C1 = ODT rac‐PZQ 20 mg/kg dispersed in water, fed; C2 = ODT rac‐PZQ 60 mg/kg dispersed in water, fed; D1 = ODT rac‐PZQ 40 mg/kg dispersed in water, fasted; D2 = Cysticide 40 mg/kg as crushed tablets, fed.
For study EMR 200661001: A = ODT LPZQ 20 mg/kg dispersed in water, fed; B = Cysticide® 40 mg/kg given with water, fed; C1 = ODT L‐PZQ 10 mg/kg dispersed in water, fed; C2 = ODT L‐PZQ 30 mg/kg dispersed in water, fed; D = ODT L‐PZQ 20 mg/kg dispersed in water, fasted; E = ODT L‐PZQ 20 mg/kg directly disintegrated in the mouth without water, fed.