AOZORA: long-term safety and joint health in paediatric persons with haemophilia A without factor VIII inhibitors receiving emicizumab - protocol for a multicentre, open-label, phase IV clinical study.

Introduction: Persons with haemophilia A (PwHA) commonly experience regular bleeding into joints, which may result in joint damage and complications such as degenerative arthritis. Emicizumab has previously demonstrated efficacy in reducing the occurrence of joint bleeds and target joints, along with having a favourable safety profile; however, data on the long-term effects on joint health are lacking. The AOZORA study will evaluate the long-term safety and joint health of paediatric PwHA without factor (F)VIII inhibitors taking emicizumab; here, we report the details of the study protocol and baseline data.

Challenges on Multiple Endpoints in Clinical Trials: An Industry Survey in Japan.

Background: Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue.

Methods: The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017.

Multiplicity Adjustment and Sample Size Calculation in Clinical Trials with Multiple Endpoints: An Industry Survey of Current Practices in Japan.

Background: Two issues in clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, the relationship between rare events and endpoints, and the differences in multiplicity adjustment between regions, and (2) the current practice on multiplicity adjustment and sample size calculation. This article summarizes the results of the survey on the second issue.

Methods: Eligible trials for this survey fulfilled the following conditions: (1) confirmatory phase 3 trial; (2) use of multiple primary endpoints, co-primary endpoints, key secondary endpoint(s) or composite endpoint(s); (3) inclusion of Japanese participants; and (4) protocols created in 2010 or later.

A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors.

Introduction: Emicizumab is a recombinant humanized bispecific monoclonal antibody mimicking the cofactor function of activated factor VIII.

Aim: In this multicentre, open-label study (HOHOEMI), we evaluated the efficacy, safety and pharmacokinetics of emicizumab in Japanese paediatric patients aged <12 years with severe haemophilia A without factor VIII (FVIII) inhibitors.

Methods: Emicizumab was administered subcutaneously, with four loading doses of 3 mg/kg every week followed by maintenance doses of 3 mg/kg every 2 weeks (Q2W) or 6 mg/kg every 4 weeks (Q4W) in 6 and 7 patients, respectively.

Challenges on Multiple Endpoints in Clinical Trials: An Industry Survey in Japan.

Background: Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue.

Methods: The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017.

Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study).

Objective: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).

Methods: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.

Current Practice on Multiplicity Adjustment and Sample Size Calculation in Multi-arm Clinical Trials: An Industry Survey in Japan.

Background: This study provides the results of a survey on the current practice of multiplicity adjustment and sample size calculation in multi-arm clinical trials.

Methods: The survey was aimed at members of the Japan Pharmaceutical Manufacturers Association (JPMA) and was conducted in 2015.

Results: Of the 66 JPMA member companies, effective responses were obtained on 151 trials from 33 companies based in Japan and 11 companies based in other countries.

Higher response with bone mineral density increase with monthly injectable ibandronate 1 mg compared with oral risedronate in the MOVER study.

We examined response to bone mineral density (BMD) gains in the MOVER study following treatment with intravenous (IV) ibandronate 1 mg/month, and investigated the characteristics of a non-responder group. At 1 year, responder rates for patients with BMD increases >0 % were similar with IV ibandronate 0.5 or 1 mg/month and oral risedronate 2.

A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia.

Background: Bitopertin, a glycine reuptake inhibitor, was investigated as a novel treatment for schizophrenia. We report all the results of a double-blind randomized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia.

Methods: This study enrolled Japanese outpatients with schizophrenia who met criteria for either "negative symptoms", i.

Effect of monthly intravenous ibandronate injections on vertebral or non-vertebral fracture risk in Japanese patients with high-risk osteoporosis in the MOVER study.

We examined the efficacy of intravenous (IV) ibandronate 1 mg/month in patient subgroups in the phase III MOVER study. Here we present results of analyses on the incidence of fractures in patients with prevalent vertebral fractures (1 or ≥2, and ≥3) at screening and femoral neck (FN) bone mineral density (BMD) T scores ≥-2.5 or <-2.

Increased bone mineral density with monthly intravenous ibandronate contributes to fracture risk reduction in patients with primary osteoporosis: three-year analysis of the MOVER study.

The relationship between gains in bone mineral density (BMD) in the hip and the incidence of vertebral fractures in the MOVER study was examined. Japanese patients from the ibandronate and risedronate treatment groups whose hip BMD had increased during the 3-year treatment period were classified into those with or without vertebral fractures. In both the ibandronate group and the risedronate group, hip BMD gains in the patients who had developed no vertebral fractures during the treatment period were greater than in the patients who developed vertebral fractures.

Stroke risk and antihypertensive drug treatment in the general population: the Japan arteriosclerosis longitudinal study.

Objective: To evaluate the association between stroke risk and blood pressure (BP) levels with regard to the usage of antihypertensive medications.

Methods: From the Japan arteriosclerosis longitudinal study, 11,371 participants from the four population-based cohort studies (aged 40-89) were followed up for a mean of 9.5 years.