Pharmacodynamics and Pharmacokinetics of AMG 531, a Thrombopoiesis‐Stimulating Peptibody, in Healthy Japanese Subjects: A Randomized, Placebo‐Controlled Study

Kumagai, Yoshito; Fujita, Tomoe; Ozaki, Machiko; Sahashi, Kunihiko; Ohkura, Masayuki; Ohtsu, Tomoko; Arai, Yoshihiro; Sonehara, Yusuke; Nichol, Janet L.

doi:10.1177/0091270007306563

Cited by 62 publications

(40 citation statements)

References 22 publications

(33 reference statements)

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“…The incidence of chronic ITP in adults in Japan is estimated to be 500-2000 cases annually, a rate of incidence similar to that seen in Western countries [1,21,22]. The safety, pharmacodynamics, and pharmacokinetics of romiplostim in Japanese adult patients were demonstrated in a phase I study and were consistent with those seen previously in healthy non-Japanese subjects [21].…”

Section: Introductionsupporting

confidence: 71%

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura

et al. 2009

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This phase II, multicenter, open-label, sequential-cohort, dose-escalation study was designed to evaluate the safety and efficacy of romiplostim, a novel peptibody that increases platelet production, in Japanese patients with chronic immune thrombocytopenic purpura (ITP). Sequential cohorts of four patients each received romiplostim (1, 3, or 6 microg/kg) subcutaneously on days 1 and 8 of the dose-escalation phase. Patients who achieved platelet responses (doubling of baseline platelet counts to > or =50 x 10(9)/L) continued romiplostim weekly during the treatment-continuation phase. Romiplostim produced dose-dependent increases in mean and peak platelet counts. Five patients received romiplostim during the treatment-continuation phase, with platelet counts > or =50 x 10(9)/L maintained in approximately half of the weekly assessments. Romiplostim was well tolerated. No severe, serious, or life-threatening adverse events were reported. No binding antibodies to romiplostim or thrombopoietin were detected. Romiplostim is safe and well tolerated in Japanese patients with chronic ITP and is effective in producing platelet count increases, consistent with the results from studies in non-Japanese patients. On the basis of these findings, a starting dose of 3 microg/kg was recommended for phase III evaluation of romiplostim in Japanese patients with chronic ITP.

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Section: Introductionsupporting

confidence: 71%

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura

et al. 2009

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“…90,[92][93][94][95][96][97][98] In 2 parallel, placebo-controlled, double-blind randomized phase 3 trials, romiplostim was given to 63 splenectomized and 62 non-splenectomized patients for 6 months. 93 An overall platelet response rate (Ն 4 out of 24 study weeks Ͼ 50 ϫ 10 9 /L) was observed in 79% and 88% of romiplostimtreated patients, compared with 0% and 14% in the respective placebo arms.…”

Section: Diagnosis and Treatment Of Immune Thrombocytopenia 173mentioning

confidence: 99%

“…A number of studies with TPOreceptor agonists have shown encouraging results in adults. 90,[92][93][94][95][96][97][98] However, no finalized studies in children are available to support the use of these agents in this patient population. Assuming that the long-term safety of these agents is confirmed, they could be used not only for children with chronic refractory ITP, but also in those with persistent but highly symptomatic disease resistant to usual first-line treatments.…”

Section: Treatment Options For Children With Persistent or Chronic Itpmentioning

confidence: 99%

International consensus report on the investigation and management of primary immune thrombocytopenia

Provan¹,

Stasi

Newland³

et al. 2010

Blood

1,835

1,954

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IntroductionPrimary immune thrombocytopenia (ITP) is an acquired immunemediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 ϫ 10 9 /L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia. 1 Until recently, the abbreviation ITP stood for idiopathic thrombocytopenic purpura, but current awareness relating to the immune-mediated nature of the disease, and the absence or minimal signs of bleeding in a large proportion of cases have led to a revision of the terminology. 1 Concepts surrounding the mechanisms of thrombocytopenia in ITP have shifted from the traditional view of increased platelet destruction mediated by autoantibodies to more complex mechanisms in which both impaired platelet production and T cell-mediated effects play a role. [2][3][4][5][6] Recent epidemiologic data suggest that the incidence in adults is approximately equal for the sexes except in the mid-adult years (30-60 years), when the disease is more prevalent in women. 7,8 ITP is classified by duration into newly diagnosed, persistent (3-12 months' duration) and chronic (Ն 12 months' duration). 1 Whereas ITP in adults typically has an insidious onset with no preceding viral or other illness and it normally follows a chronic course, 9 ITP in children is usually short-lived with at least two-thirds recovering spontaneously within 6 months. 10 Signs and symptoms vary widely. Many patients have either no symptoms or minimal bruising, whereas others experience serious bleeding, which may include gastrointestinal hemorrhage (GI), extensive skin and mucosal hemorrhage, or intracranial hemorrhage (ICH). The severity of thrombocytopenia correlates to some extent but not completely with the bleeding risk. 7,11 Additional factors (eg, age, lifestyle factors, uremia) affect the risk and should be evaluated before the appropriate management is determined.The investigation and management of ITP patients vary widely. The purpose of this consensus document is to comment on new data and provide recommendations relating to diagnosis and treatment. Final judgment regarding care of individual patients should, however, lie with the responsible health care professional and be based on careful investigation of individual circumstances. MethodsComposition of the panel. The panel included 22 members with recognized clinical and research expertise in ITP representing North America (United States, 7; Canada, 1), Europe (France, 1; Italy, 2; Spain, 1; Switzerland, 1; United Kingdom, 8), and Australia (1).Assessment of the literature. Articles were identified by a computer-assisted search of the literature published in English using the National Library of Medicine PubMed database. The For personal use only. on May 7, 2018. by guest www.bloodjournal.org From search criteria were: 'immune thrombocytopenic purpura', 'idiopathic thrombocytopenic purpura', 'ITP', and 'autoimmune thrombocytopenic purpura'. A subsequent search was performed using the corresponding MedLin...

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“…[23][24][25] Japanese subjects when compared with previous studies of these agents in non-Japanese populations. [17][18][19]26) Haemophilia A is a relatively rare disease. 27) Although the A-LONG study is one of the largest global studies conducted in haemophilia A, there were 14 Japanese subjects included.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the safety, pharmacokinetics, and efficacy of recombinant factor VIII fc fusion protein in Japanese subjects with severe haemophilia A: analysis from the A-LONG study

Hanabusa

Shima

Nogami

et al. 2016

Nihon Kessen Shiketsu Gakkaishi

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Japanese subjects in the individualised prophylaxis, weekly prophylaxis, and episodic arms were 3.56, 4.34, and 25.06, respectively. Most bleeding episodes (89.5%) resolved with 1 rFVIIIFc injection. No inhibitors were reported; safety findings were comparable to non-Japanese subjects. Conclusion: rFVIIIFc was safe and efficacious for control and prevention of bleeding in Japanese subjects, with outcomes comparable to non-Japanese subjects.

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Pharmacodynamics and Pharmacokinetics of AMG 531, a Thrombopoiesis‐Stimulating Peptibody, in Healthy Japanese Subjects: A Randomized, Placebo‐Controlled Study

Cited by 62 publications

References 22 publications

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura

International consensus report on the investigation and management of primary immune thrombocytopenia

Evaluation of the safety, pharmacokinetics, and efficacy of recombinant factor VIII fc fusion protein in Japanese subjects with severe haemophilia A: analysis from the A-LONG study

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