Michihiro Takahashi

A randomized, double-blind, placebo-controlled study of atomoxetine in Japanese children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVES Until the recent approval of methylphenidate (MPH), Japan had no approved treatment for attention-deficit/hyperactivity disorder (ADHD). The need still exists for an effective, safe, nonstimulant treatment. This first placebo-controlled Japan study of an ADHD nonstimulant therapy assessed atomoxetine efficacy and safety to determine the optimal dose for controlling ADHD symptoms in children and adolescents. METHODS A total of 245 Japanese children and adolescents, aged 6-17 years and diagnosed with ADHD, were randomly assigned to receive placebo or one of three atomoxetine doses (0.5, 1.2, and 1.8 mg/kg per day) over 8 weeks. Symptoms were assessed with the Japanese Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator scored and integrated with teacher reports (ADHD RS-IV-J:I/Sch). Adverse events, vital signs, laboratory tests, and electrocardiograms (ECGs) were obtained for safety analysis. RESULTS In all, 234 patients completed the study. Atomoxetine at 1.8 mg/kg per day was significantly superior to placebo in reducing ADHD symptoms (p = 0.01; one-sided). Decreased appetite and vomiting were significantly greater in the atomoxetine treatment groups; however, no clinically significant differences were observed. Two patients discontinued due to affect lability and headache. A linear dose-response and vital signs similar to those from other atomoxetine studies were observed. CONCLUSION Atomoxetine provides an effective and safe nonstimulant option for the treatment of Japanese pediatric patients with ADHD.

Efficacy and Safety of Atomoxetine Hydrochloride in Asian Adults With ADHD: A Multinational 10-Week Randomized Double-Blind Placebo-Controlled Asian Study

Objective: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication. Method: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners’ Adult ADHD Rating Scale–Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function. Results: Atomoxetine treatment resulted in a mean reduction of −14.3 (placebo, −8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%). Conclusion: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients.

Efficacy and safety of olanzapine in the treatment of Japanese patients with bipolar I disorder in a current manic or mixed episode: a randomized, double-blind, placebo- and haloperidol-controlled study.

BACKGROUND No current data were available regarding the efficacy and safety of olanzapine in Japanese patients with bipolar I disorder with a current manic/mixed episode. METHODS Patients received blindly olanzapine (5-20 mg/day; N=105), haloperidol (2.5-10 mg/day; N=20), or placebo (N=99) for 3 weeks. For the following 3 weeks, the olanzapine and haloperidol groups continued their treatment, while the placebo group switched blindly to olanzapine. The primary efficacy measure was the mean change in Young Mania Rating Scale (YMRS) total score; secondary efficacy measures included bipolar disorder remission rate and switch-to depression. Safety measures included treatment-emergent adverse events (TEAEs), weight and extrapyramidal symptoms (EPSs). RESULTS YMRS total score significantly decreased in the olanzapine group compared with the placebo group (-5.62 [95% CI: -8.87, -2.37], p<0.001) after 3 weeks. Compared with haloperidol, olanzapine was not markedly different in improving overall bipolar symptomatology, and fewer olanzapine-treated patients switched to symptomatic depression (2.4% vs 16.7%, p=0.014). Overall incidences of TEAEs were not significantly different among the groups, and EPSs in olanzapine group were less severe than in the haloperidol group. LIMITATIONS The small haloperidol sample size limited the conclusions that can be drawn from the statistical comparisons between the active treatments. CONCLUSIONS This was the first study to evaluate an atypical antipsychotic in Japanese patients with manic bipolar I disorder. Consistent with previous non-Japanese studies, olanzapine was generally well-tolerated and superior to placebo in improving the severity of manic symptoms. Compared to haloperidol, fewer olanzapine-treated patients switched to symptomatic depression, and EPSs were less severe.

An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

Aims:  The main purpose of this first atomoxetine study in Japanese adults with attention‐deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8‐week treatment regimen.

Open‐label, dose‐titration tolerability study of atomoxetine hydrochloride in Korean, Chinese, and Taiwanese adults with attention‐deficit/hyperactivity disorder

The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention‐deficit/hyperactivity disorder (ADHD).

Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Japanese subpopulation analysis of a randomized, double-blind, placebo-controlled study

BackgroundThe efficacy and safety of olanzapine monotherapy are evaluated in Japanese patients from a large, global study of bipolar depression.MethodsThis is an analysis of Japanese patients from a 6-week, global (Japan, China, Korea, Taiwan, and the United States), randomized, double-blind, placebo-controlled, Phase 3 study of patients with a depressive episode of bipolar I disorder. The primary outcome was baseline-to-endpoint change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcome measures included the Clinical Global Impressions-Bipolar Version Severity of Illness Scale (CGI-BP), the 17-item Hamilton Depression Rating Scale (HAMD-17) total score, the Young Mania Rating Scale (YMRS) total score, and rates of response (≥50% baseline-to-endpoint reduction in MADRS total score), recovery, and remission.ResultsOf the 156 Japanese patients, 104 had been allocated to olanzapine and 52 to placebo. All results are baseline-to-endpoint change. Compared to placebo, patients in the olanzapine group experienced greater improvement in the primary outcome measure, MADRS total score (−14.9 vs. −10.7; p = .01). They also had greater reductions in the following secondary measures: CGI- BP Depression (−1.41 vs. -0.89; p = .008), CGI-BP Bipolar (−1.31 vs. −0.83; p = .01), HAMD-17 (−11.7 vs. −7.9; p < .01), and YMRS (-0.32 vs. 0.34; p = .03). Differences in rates of response, recovery, and remission were not statistically significant. A greater proportion of olanzapine-treated patients reported treatment- emergent adverse events (87.5% vs. 59.6%; p < .001). Patients treated with olanzapine had greater increases in weight (p < .001) and fasting total cholesterol (p = .008); fasting triglycerides (p = .02), and fasting low-density lipoprotein (p = .01). There was a greater reduction in fasting high-density lipoprotein in olanzapine-treated patients (p = .01). Compared with placebo-group patients, more olanzapine-group patients shifted from borderline to high cholesterol (25.0% vs. 0.0%; p = .007) and had clinically significant weight gain (≥7% body weight) (20.2% vs. 1.9%; p = .001).ConclusionsResults of this analysis support the efficacy and tolerability of olanzapine for the treatment of bipolar depression in Japanese patients. Results in this population were consistent with those seen in the more ethnically diverse parent study. In making treatment decisions for individual patients, clinicians should carefully consider the risks and benefits of olanzapine treatment.Trial RegistrationClinicatrials.gov ID NCT00510146 Olanzapine Treatment of Patients with Bipolar I Disorder

Long-term safety and tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder.

The primary aim of this study was to evaluate the long‐term safety/tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder (ADHD).

Solanezumab was safe and well-tolerated for Asian patients with mild-to-moderate Alzheimer's disease in a multicenter, randomized, open-label, multi-dose study

Background: Solanezumab is a humanized anti-amyloid-b monoclonal antibody being developed as a passive-immunization treatment to slow the progression of AD. It recognizes a mid-domain epitope of the amyloid-b (Ab) peptide and elicits continuous changes of Ab dynamics. Although multiple doses of solanezumab are safe and well tolerated in non-Japanese, there are no data available in Asians. This is the first study to describe the safety and tolerability of multiple doses of solanezumab in Asian patients with mild-to-moderate AD. Methods: This study was a multicenter, randomized, open-label, parallel study in Japan. Duration was 5 days to 5 weeks in Period I (eligibility), 8 weeks in Period II (treatment), and 16 weeks in Period III (follow-up). Patients were randomized 1:1:1 to 3 solanezumab dose arms: iv infusions of 400 mg once every week (QW group), 400 mg once every four weeks (Q4W group) and 400 mg once every eight weeks (Q8W group). All patients visited every week and blood samples were taken for safety, pharmacokinetics, and pharmacodynamics. Results: Thirty five patients entered the study. Thirty three patients were randomly assigned to treatment, received at least one dose of study drug, and completed the study. Eighteen patients (54.5%) were female, fifteen patients (45.5%) were male, and their ages ranged from 56 to 84 years (mean 1⁄4 70.7). There were no serious adverse events related to solanezumab; although treatment-emergent adverse events (TEAEs) were reported in 8 patients from the Q8W group (66.7%), 5 patients from the Q4W group (50.0%), and 5 patients from the QW group (45.5%). Adverse events reported were mild or moderate except one event. Only one event (pain in extremity) was judged as severe but was not related to the study drug or a study procedure. There were no infusion reactions, MRI evidence of meningoencephalitis, or clinically meaningful laboratory abnormalities. Conclusions: Solanezumab was safe and well-tolerated up to 400 mg once a week in Asian (Japanese) AD patients.

Efficacy and safety of atomoxetine hydrochloride in Korean adults with attention‐deficit hyperactivity disorder

This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention‐deficit hyperactivity disorder (ADHD).

A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

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