2006 12 08 2008 04 11 2008 10 13 2009 10 15 2011 03 30 2011 09 21 2013 03 29 2015 01 30 2016 11 07 2017 08 25 -β CHO - β CHO β Recombinant Human Erythropoietin β InjectionChongzu Ren Hongxibaoshengchengsu eta B Zhusheye Recormon Recombinant Human Erythropoietin β Injection (CHO Cell) Chongzu Ren Cuhongsu Beta Zhusheye CHO Xibao -β CHO -20, 1/12
2000IU/0.3ml/ -β CHO 0.3 ml 4000IU/0.3ml/ -β CHO 0.3 ml 5000IU/0.3ml/ -β CHO 0.3 ml 10000IU/0.6ml/ β CHO 0.6 ml 12g/dl 7.5mmol/l 2 10g/dl 6.2mmol/l 12g/dl 7.5mmol/l 12g/dl 7.5mmol/l 12g/dl 7.5mmol/l 4 2g/dl 1.25mmol/l 2g/dl 1.25mmol/l 12g/dl 7.45mmol/l 25 25 2/12
1 3 20 IU/kg <0.25g/dl, 4 3 20 IU/kg 3 20 IU/kg 4 80 IU/kg 3 20 IU/kg 3 720IU/kg 2 10 12g/dl 1 3 7 24 10g/dl 6.2mmol/l 3 7 30000IU/ 450IU/kg 10g/dl 6.2mmol/l 12g/dl 7.5mmol/l 12g/dl 7.5mmol/l 12g/dl 7.5mmol/l 3/12
4 1g/dl 0.62 mmol/l 1g/dl 0.62 mmol/l 8 1g/dl 0.62 mmol/l 4 60,000 IU 25 50% 12g/dl 7.5mmol/l 25 50% 13g/dl 8.1mmol/l 12g/dl 7.5mmol/l 25 4 2g/dl 1.3mmol/l 12g/dl 7.5mmol/l 25 50 1725 8% PCV PRCA PRCA >0.1%, <1% >1% <10% >1%, <10% >0.01%, <0.1% <0.01% 4/12
β >1%, <10% 7% 4% >1%, <10% >1%, <10% >1%, <10% -β 1/10.000 1/1.000 1/10.000 1/10.000 / B 12 5/12
PCV 8 12g/dl 7.5 mmol/l ESAs 12 14 EPO - 14g /dl 8.7mmol/l - 12-14g/dl 7.5-8.7mmol/l - 12g/dl 7.5mmol/l ESAs 10-12g/dL 6/12
/ 0.3mg 1mmol 23mg -β 7/12
-β 2833 5 4 1 2 >13g/dl 3 12g/dl 14g/dl 1 4 1.25 2.47 Meta 12 1.13 95% CI 0.87, 1.46 10g/dl (n=899) 0.98 95 % CI 0.68 1.40 RR 1.62, 95% CI: 1.13, 2.31 57 9000 meta 1.08 95 % CI: 0.99, 1.18;42 8167 6769 13g/dl PRCA ML17616 74 12 38,36 150IU Kg 8/12
ITT intention -to-treat 68.4% 36.1% PP per -protocol population 73.5% 46.4 1 2 1. ITT g/l ± 78.03 ±12.80 (38 ) 74.89 ±11.53 (36 ) 78.50 (55.00,100.00 ) 74.50 (43.00,99.00 ) 1 ± 83.97 ±16.55 (35 ) 77.93 ±15.95 (30 ) 82.00 (55.00,113.00 ) 75.00 (45.00,126.00 ) 2 ± 89.88 ±16.91 (34 ) 81.43 ±18.80 (30 ) 92.50 (61.00,122.00 ) 80.00 (43.00,127.00 ) 3 ± 96.96 ±17.15 (28 ) 86.25 ±18.57 (24 ) 94.00 (67.00,125.00 ) 84.50 (51.00,128.00 ) 4 ± 97.83 ±20.36 (35 ) 85.00 ±21.01 (27 ) 94.00 (53.00,135.00 ) 82.00 (50.00,130.00 ) 6 ± 102.59 ±21.44 (32 ) 89.74 ±21.50 (23 ) 101.50 (69.00,142.00 ) 88.00 (52.00,125.00 ) 8 ± 105.45 ±21.50 (33 ) 87.12 ±23.41 (26 ) 105.00 (69.00,146.00 ) 90.50 (45.00,135.00 ) 10 118.19 ±29.12 (26 ) 83.63 ±26.70 (19 ) 115.00 (74.00,209.00 ) 76.00 (38.00,133.00 ) 12 ± 109.70 ±24.88 (27 ) 93.21 ±22.30 (24 ) 108.00 (60.00,156.00 ) 93.00 (55.00,122.00 ) 2. PP g/l ± 77.62 ±12.24 (34 ) 76.54 ±10.72 (28 ) (- ) 78.50 (55.00,99.00 ) 74.50 (58.00,99.00 ) 1 ± 83.16 ±15.53 (31 ) 79.83 ±16.21 (24 ) 81.00 (58.00,113.00 ) 75.50 (57.00,126.00 ) 2 ± 89.45 ±16.42 (31 ) 83.76 ±18.63 (25 ) 92.00 (61.00,122.00 ) 81.00 (48.00,127.00 ) 3 ± 96.00 ±17.40 (26 ) 86.70 ±18.85 (23 ) 93.50 (67.00,125.00 ) 86.00 (51.00,128.00 ) 4 ± 96.67 ±20.39 (33 ) 85.00 ±21.01 (27 ) 93.00 (53.00,135.00 ) 82.00 (50.00,130.00 ) 6 ± 101.84 ±21.36 (31 ) 89.74 ±21.50 (23 ) 101.00 (69.00,142.00 ) 88.00 (52.00,125.00 ) 8 ± 105.06 ±21.73 (32 ) 87.12 ±23.41 (26 ) 105.00 (69.00,146.00 ) 90.50 (45.00,135.00 ) 10 118.28 ±29.72 (25 ) 83.63 ±26.70 (19 ) 115.00 (74.00,209.00 ) 76.00 (38.00,133.00 ) 12 ± 109.38 ±25.31 (26 ) 93.21 ±22.30 (24 ) 108.00 (60.00,156.00 ) 93.00 (55.00,122.00 ) ML17620 9/12
12 61 60 150IU Kg ITT intention-to-treat 47.5 % PP61.7% ITT intention-to-treat 23.3 % PP per -protocol population 31.8% 3 4 3. ITT ± 1 ± 2 ± 3 ± 4 ± 6 ± 8 ± 10 12 ± g/l 91.10 ±11.60 (61 ) 93.44 ±10.65 (60 ) 91.00 (65.00,110.00 ) 94.00 (63.50,110.00 ) 94.69 ±18.21 (58 ) 98.09 ±14.12 (56 ) 93.00 (60.00,147.00 ) 99.00 (59.00,129.00 ) 96.24 ±19.25 (52 ) 94.10 ±14.83 (44 ) 93.50 (52.00,143.00 ) 95.50 (58.00,123.00 ) 98.04 ±22.36 (50 ) 95.41 ±16.03 (46 ) 96.00 (40.00,152.00 ) 95.00 (56.00,132.00 ) 104.50 ±21.31 (54 ) 98.42 ±17.72 (49 ) 103.50 (55.20,156.00 ) 101.00 (56.00,132.00 ) 103.81 ±23.09 (44 ) 97.84 ±16.61 (51 ) 104.50 (54.20,149.00 ) 98.00 (63.00,134.00 ) 107.74 ±21.23 (42 ) 102.14 ±17.61 (38 ) 108.00 (46.00,152.00 ) 102.00 (60.00,136.00 ) 110.84 ±23.15 (33 ) 101.03 ±16.70 (32 ) 111.00 (52.00,163.00 ) 99.00 (61.00,135.00 ) 112.59 ±20.86 (32 ) 105.21 ±16.70 (29 ) 114.35 (74.20,164.00 ) 106.00 (70.00,137.00 ) 4. PP 1 2 3 4 6 ± (n) ± (n) ± (n) ± (n) ± (n) ± (n) g/l 91.83 ±11.62 (47 ) 94.49 ±10.21 (44 ) 93.00 (65.00,109.00 ) 95.00 (63.50,110.00 ) 96.34 ±18.87 (46 ) 99.91 ±13.34 (42 ) 94.50 (60.00,147.00 ) 99.50 (68.00,129.00 ) 96.74 ±19.25 (44 ) 96.13 ±13.61 (35 ) 95.00 (52.00,143.00 ) 97.00 (68.50,123.00 ) 98.26 ±21.08 (43 ) 98.02 ±15.74 (38 ) 96.00 (40.00,145.00 ) 98.50 (56.00,132.00 ) 105.01 ±20.54 (47 ) 99.43 ±17.80 (41 ) 103.00 (66.00,156.00 ) 104.00 (63.00,132.00 ) 105.64 ±21.85 (42 ) 98.95 ±17.12 (43 ) 106.00 (57.00,149.00 ) 98.00 (63.00,134.00 ) 10/12
8 ± (n) 10 ± (n) 12 ± (n) 107.74 ±21.23 (42 ) 102.14 ±17.61 (38 ) 108.00 (46.00,152.00 ) 102.00 (60.00,136.00 ) 110.84 ±23.15 (33 ) 101.03 ±16.70 (32 ) 111.00 (52.00,163.00 ) 99.00 (61.00,135.00 ) 112.59 ±20.86 (32 ) 105.21 ±16.70 (29 ) 114.35 (74.20,164.00 ) 106.00 (70.00,137.00 ) -β -β β β3h - -β β -β -β4 12 1 2 -β 28 13 28 -β 23 42% 2 8 2000IU/0.3ml/4000IU/0.3ml/ 5000IU/0.3ml/ 10000IU/0.6ml/6 / 11/12
24 Roche Pharma (Schweiz) Ltd. Schoenmattstrasse 4153 2 Reinach Switzerland Roche Diagnostics GmbH Sandhofer strasse 116 68305 Mannheim, Germany 1100 201203 (021)28922888 (021)50801800 400-820-8780800-820-8780 9:00-18:00 Recormon 12/12