Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis

Kei Hori, Yoshio Taguma, Kiyotsugu Omae, Jun Ino, Takumi Yoshida, Tetsuya Oishi, Takahiro Mochizuki, Satoshi Hijiya, Kenichi Oguchi, Susumu Uda, Mikio Wakasa, Takao Shoji, Yuichiro Fukudome, Michiyasu Hatano, Yutaka Kanno, Yukio Yuzawa, Kunio Morozumi, Chikao Yamazaki, Shizunori Ichida, Mikito TsuyukiTomohiko Naruse, Daijyo Inaguma, Kei Kurata, Hiroshi Kitamura, Terumasa Hayashi, Atsushi Yamauchi, Yasushi Saika, Yoshihiko Saito, Kazuhito Takeda, Akiyo Shiroozu, Hideki Hirakata, Kazuhiko Tsuruya, Masami Bessho, Yoshiharu Tsubakihara, Masashi Suzuki

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: C. E. R. A. (Continuous Erythropoietin Receptor Activator) is an innovative erythropoiesis stimulating agent (ESA) with unique activity toward erythropoietin receptor, and results in showing significantly prolonged half-life. These studies were planned to evaluate the appropriate dose of C. E. R. A. administered either SC or IV once every 2 weeks (Q2W) to correct renal anemia in Japanese CKD patients not on dialysis. Methods: C. E. R. A. was administered SC (77 patients) or IV (57 patients) at three dose levels of 25, 50 or 75 μg Q2W to attain the Hb level of 12 g/dL (correction period) for patients with Hb levels of < 10 g/dL. Once this Hb level had been attained, C. E. R. A. was administered Q4W at the dose levels ranging from 15 to 300 μg (SC) or 25 to 300 μg (IV) to maintain Hb levels within 11-13g/dL (maintenance period). The total observation period in these studies was 48-50 weeks. Primary endpoint is the slope of the Hb level/time curve (g/dL/week). Secondary endpoints are the percentage of patients who achieved the target Hb level of 12 g/dL and the time taken to reach target level in correction period, and the percentage of patients to maintain the target Hb levels of 11-13 g/dL in maintenance period. Results: Mean (SD) slopes of the Hb/time curves with SC administration of Q2W C. E. R. A. at each of 25, 50 or 75 μg were 0.100 (0.108), 0.227 (0.137) or 0.303 (0.159) g/dL/week, and those with IV were 0.129 (0.118), 0.352 (0.219) or 0.412 (0.174) g/dL/week (IV), respectively, which were similar between SC and IV route at the same dose. At each dose of 25, 50 or 75 μg, the percentages of patients achieving the Hb level of 12 g/dL were 75.0, 92.0 or 84.6% (SC), 84.2, 95.0 or 100% (IV), respectively, and the time to achieve Hb target was 140, 112 or 84 days (SC) and 112, 70 or 55.5 days (IV), in which both endpoints found to be dose-related. The percentages of the patients maintained Hb target levels (11-13 g/dL) after 24 week and 48 weeks were 81.1% and 72.7% (SC) and 73.3% and 85.0% (IV), respectively. Conclusions: These studies have demonstrated that a dose of C. E. R. A. Q2W as low as 25 μg, provides a smooth and steady increase in Hb levels in Japanese patients with CKD not on dialysis, regardless of administration route. Furthermore, administration of C. E. R. A. Q4W successfully maintained target Hb levels in this patient population.

Original languageEnglish
JournalJapanese Pharmacology and Therapeutics
Volume39
Issue numberSUPPL. 1
Publication statusPublished - May 10 2011

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Chronic Renal Insufficiency
Dialysis
Maintenance
continuous erythropoietin receptor activator
Hematinics
Erythropoietin Receptors
Half-Life
Anemia
Observation
Kidney

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis. / Hori, Kei; Taguma, Yoshio; Omae, Kiyotsugu; Ino, Jun; Yoshida, Takumi; Oishi, Tetsuya; Mochizuki, Takahiro; Hijiya, Satoshi; Oguchi, Kenichi; Uda, Susumu; Wakasa, Mikio; Shoji, Takao; Fukudome, Yuichiro; Hatano, Michiyasu; Kanno, Yutaka; Yuzawa, Yukio; Morozumi, Kunio; Yamazaki, Chikao; Ichida, Shizunori; Tsuyuki, Mikito; Naruse, Tomohiko; Inaguma, Daijyo; Kurata, Kei; Kitamura, Hiroshi; Hayashi, Terumasa; Yamauchi, Atsushi; Saika, Yasushi; Saito, Yoshihiko; Takeda, Kazuhito; Shiroozu, Akiyo; Hirakata, Hideki; Tsuruya, Kazuhiko; Bessho, Masami; Tsubakihara, Yoshiharu; Suzuki, Masashi.

In: Japanese Pharmacology and Therapeutics, Vol. 39, No. SUPPL. 1, 10.05.2011.

Research output: Contribution to journalArticle

Hori, K, Taguma, Y, Omae, K, Ino, J, Yoshida, T, Oishi, T, Mochizuki, T, Hijiya, S, Oguchi, K, Uda, S, Wakasa, M, Shoji, T, Fukudome, Y, Hatano, M, Kanno, Y, Yuzawa, Y, Morozumi, K, Yamazaki, C, Ichida, S, Tsuyuki, M, Naruse, T, Inaguma, D, Kurata, K, Kitamura, H, Hayashi, T, Yamauchi, A, Saika, Y, Saito, Y, Takeda, K, Shiroozu, A, Hirakata, H, Tsuruya, K, Bessho, M, Tsubakihara, Y & Suzuki, M 2011, 'Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis', Japanese Pharmacology and Therapeutics, vol. 39, no. SUPPL. 1.
Hori, Kei ; Taguma, Yoshio ; Omae, Kiyotsugu ; Ino, Jun ; Yoshida, Takumi ; Oishi, Tetsuya ; Mochizuki, Takahiro ; Hijiya, Satoshi ; Oguchi, Kenichi ; Uda, Susumu ; Wakasa, Mikio ; Shoji, Takao ; Fukudome, Yuichiro ; Hatano, Michiyasu ; Kanno, Yutaka ; Yuzawa, Yukio ; Morozumi, Kunio ; Yamazaki, Chikao ; Ichida, Shizunori ; Tsuyuki, Mikito ; Naruse, Tomohiko ; Inaguma, Daijyo ; Kurata, Kei ; Kitamura, Hiroshi ; Hayashi, Terumasa ; Yamauchi, Atsushi ; Saika, Yasushi ; Saito, Yoshihiko ; Takeda, Kazuhito ; Shiroozu, Akiyo ; Hirakata, Hideki ; Tsuruya, Kazuhiko ; Bessho, Masami ; Tsubakihara, Yoshiharu ; Suzuki, Masashi. / Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis. In: Japanese Pharmacology and Therapeutics. 2011 ; Vol. 39, No. SUPPL. 1.
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title = "Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis",
abstract = "Background: C. E. R. A. (Continuous Erythropoietin Receptor Activator) is an innovative erythropoiesis stimulating agent (ESA) with unique activity toward erythropoietin receptor, and results in showing significantly prolonged half-life. These studies were planned to evaluate the appropriate dose of C. E. R. A. administered either SC or IV once every 2 weeks (Q2W) to correct renal anemia in Japanese CKD patients not on dialysis. Methods: C. E. R. A. was administered SC (77 patients) or IV (57 patients) at three dose levels of 25, 50 or 75 μg Q2W to attain the Hb level of 12 g/dL (correction period) for patients with Hb levels of < 10 g/dL. Once this Hb level had been attained, C. E. R. A. was administered Q4W at the dose levels ranging from 15 to 300 μg (SC) or 25 to 300 μg (IV) to maintain Hb levels within 11-13g/dL (maintenance period). The total observation period in these studies was 48-50 weeks. Primary endpoint is the slope of the Hb level/time curve (g/dL/week). Secondary endpoints are the percentage of patients who achieved the target Hb level of 12 g/dL and the time taken to reach target level in correction period, and the percentage of patients to maintain the target Hb levels of 11-13 g/dL in maintenance period. Results: Mean (SD) slopes of the Hb/time curves with SC administration of Q2W C. E. R. A. at each of 25, 50 or 75 μg were 0.100 (0.108), 0.227 (0.137) or 0.303 (0.159) g/dL/week, and those with IV were 0.129 (0.118), 0.352 (0.219) or 0.412 (0.174) g/dL/week (IV), respectively, which were similar between SC and IV route at the same dose. At each dose of 25, 50 or 75 μg, the percentages of patients achieving the Hb level of 12 g/dL were 75.0, 92.0 or 84.6{\%} (SC), 84.2, 95.0 or 100{\%} (IV), respectively, and the time to achieve Hb target was 140, 112 or 84 days (SC) and 112, 70 or 55.5 days (IV), in which both endpoints found to be dose-related. The percentages of the patients maintained Hb target levels (11-13 g/dL) after 24 week and 48 weeks were 81.1{\%} and 72.7{\%} (SC) and 73.3{\%} and 85.0{\%} (IV), respectively. Conclusions: These studies have demonstrated that a dose of C. E. R. A. Q2W as low as 25 μg, provides a smooth and steady increase in Hb levels in Japanese patients with CKD not on dialysis, regardless of administration route. Furthermore, administration of C. E. R. A. Q4W successfully maintained target Hb levels in this patient population.",
author = "Kei Hori and Yoshio Taguma and Kiyotsugu Omae and Jun Ino and Takumi Yoshida and Tetsuya Oishi and Takahiro Mochizuki and Satoshi Hijiya and Kenichi Oguchi and Susumu Uda and Mikio Wakasa and Takao Shoji and Yuichiro Fukudome and Michiyasu Hatano and Yutaka Kanno and Yukio Yuzawa and Kunio Morozumi and Chikao Yamazaki and Shizunori Ichida and Mikito Tsuyuki and Tomohiko Naruse and Daijyo Inaguma and Kei Kurata and Hiroshi Kitamura and Terumasa Hayashi and Atsushi Yamauchi and Yasushi Saika and Yoshihiko Saito and Kazuhito Takeda and Akiyo Shiroozu and Hideki Hirakata and Kazuhiko Tsuruya and Masami Bessho and Yoshiharu Tsubakihara and Masashi Suzuki",
year = "2011",
month = "5",
day = "10",
language = "English",
volume = "39",
journal = "Japanese Pharmacology and Therapeutics",
issn = "0386-3603",
publisher = "Life Science Publishing Co. Ltd",
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TY - JOUR

T1 - Dose-finding and long-term studies wih C. E. R. A. (Continuous Erythropoietin Receptor Activator) administered subcutaneously (SC) or intravenously (IV) in Japanese patients with chronic kidney disease (CKD) not on dialysis

AU - Hori, Kei

AU - Taguma, Yoshio

AU - Omae, Kiyotsugu

AU - Ino, Jun

AU - Yoshida, Takumi

AU - Oishi, Tetsuya

AU - Mochizuki, Takahiro

AU - Hijiya, Satoshi

AU - Oguchi, Kenichi

AU - Uda, Susumu

AU - Wakasa, Mikio

AU - Shoji, Takao

AU - Fukudome, Yuichiro

AU - Hatano, Michiyasu

AU - Kanno, Yutaka

AU - Yuzawa, Yukio

AU - Morozumi, Kunio

AU - Yamazaki, Chikao

AU - Ichida, Shizunori

AU - Tsuyuki, Mikito

AU - Naruse, Tomohiko

AU - Inaguma, Daijyo

AU - Kurata, Kei

AU - Kitamura, Hiroshi

AU - Hayashi, Terumasa

AU - Yamauchi, Atsushi

AU - Saika, Yasushi

AU - Saito, Yoshihiko

AU - Takeda, Kazuhito

AU - Shiroozu, Akiyo

AU - Hirakata, Hideki

AU - Tsuruya, Kazuhiko

AU - Bessho, Masami

AU - Tsubakihara, Yoshiharu

AU - Suzuki, Masashi

PY - 2011/5/10

Y1 - 2011/5/10

N2 - Background: C. E. R. A. (Continuous Erythropoietin Receptor Activator) is an innovative erythropoiesis stimulating agent (ESA) with unique activity toward erythropoietin receptor, and results in showing significantly prolonged half-life. These studies were planned to evaluate the appropriate dose of C. E. R. A. administered either SC or IV once every 2 weeks (Q2W) to correct renal anemia in Japanese CKD patients not on dialysis. Methods: C. E. R. A. was administered SC (77 patients) or IV (57 patients) at three dose levels of 25, 50 or 75 μg Q2W to attain the Hb level of 12 g/dL (correction period) for patients with Hb levels of < 10 g/dL. Once this Hb level had been attained, C. E. R. A. was administered Q4W at the dose levels ranging from 15 to 300 μg (SC) or 25 to 300 μg (IV) to maintain Hb levels within 11-13g/dL (maintenance period). The total observation period in these studies was 48-50 weeks. Primary endpoint is the slope of the Hb level/time curve (g/dL/week). Secondary endpoints are the percentage of patients who achieved the target Hb level of 12 g/dL and the time taken to reach target level in correction period, and the percentage of patients to maintain the target Hb levels of 11-13 g/dL in maintenance period. Results: Mean (SD) slopes of the Hb/time curves with SC administration of Q2W C. E. R. A. at each of 25, 50 or 75 μg were 0.100 (0.108), 0.227 (0.137) or 0.303 (0.159) g/dL/week, and those with IV were 0.129 (0.118), 0.352 (0.219) or 0.412 (0.174) g/dL/week (IV), respectively, which were similar between SC and IV route at the same dose. At each dose of 25, 50 or 75 μg, the percentages of patients achieving the Hb level of 12 g/dL were 75.0, 92.0 or 84.6% (SC), 84.2, 95.0 or 100% (IV), respectively, and the time to achieve Hb target was 140, 112 or 84 days (SC) and 112, 70 or 55.5 days (IV), in which both endpoints found to be dose-related. The percentages of the patients maintained Hb target levels (11-13 g/dL) after 24 week and 48 weeks were 81.1% and 72.7% (SC) and 73.3% and 85.0% (IV), respectively. Conclusions: These studies have demonstrated that a dose of C. E. R. A. Q2W as low as 25 μg, provides a smooth and steady increase in Hb levels in Japanese patients with CKD not on dialysis, regardless of administration route. Furthermore, administration of C. E. R. A. Q4W successfully maintained target Hb levels in this patient population.

AB - Background: C. E. R. A. (Continuous Erythropoietin Receptor Activator) is an innovative erythropoiesis stimulating agent (ESA) with unique activity toward erythropoietin receptor, and results in showing significantly prolonged half-life. These studies were planned to evaluate the appropriate dose of C. E. R. A. administered either SC or IV once every 2 weeks (Q2W) to correct renal anemia in Japanese CKD patients not on dialysis. Methods: C. E. R. A. was administered SC (77 patients) or IV (57 patients) at three dose levels of 25, 50 or 75 μg Q2W to attain the Hb level of 12 g/dL (correction period) for patients with Hb levels of < 10 g/dL. Once this Hb level had been attained, C. E. R. A. was administered Q4W at the dose levels ranging from 15 to 300 μg (SC) or 25 to 300 μg (IV) to maintain Hb levels within 11-13g/dL (maintenance period). The total observation period in these studies was 48-50 weeks. Primary endpoint is the slope of the Hb level/time curve (g/dL/week). Secondary endpoints are the percentage of patients who achieved the target Hb level of 12 g/dL and the time taken to reach target level in correction period, and the percentage of patients to maintain the target Hb levels of 11-13 g/dL in maintenance period. Results: Mean (SD) slopes of the Hb/time curves with SC administration of Q2W C. E. R. A. at each of 25, 50 or 75 μg were 0.100 (0.108), 0.227 (0.137) or 0.303 (0.159) g/dL/week, and those with IV were 0.129 (0.118), 0.352 (0.219) or 0.412 (0.174) g/dL/week (IV), respectively, which were similar between SC and IV route at the same dose. At each dose of 25, 50 or 75 μg, the percentages of patients achieving the Hb level of 12 g/dL were 75.0, 92.0 or 84.6% (SC), 84.2, 95.0 or 100% (IV), respectively, and the time to achieve Hb target was 140, 112 or 84 days (SC) and 112, 70 or 55.5 days (IV), in which both endpoints found to be dose-related. The percentages of the patients maintained Hb target levels (11-13 g/dL) after 24 week and 48 weeks were 81.1% and 72.7% (SC) and 73.3% and 85.0% (IV), respectively. Conclusions: These studies have demonstrated that a dose of C. E. R. A. Q2W as low as 25 μg, provides a smooth and steady increase in Hb levels in Japanese patients with CKD not on dialysis, regardless of administration route. Furthermore, administration of C. E. R. A. Q4W successfully maintained target Hb levels in this patient population.

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