Taro Goto

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.

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.

Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study.

Abstract We assessed the executive function in adults with attention-deficit/hyperactivity disorder (ADHD) during atomoxetine treatment in a randomized withdrawal trial. Responders (Conners’ ADHD Rating Scale–Investigator Rated: Screening Version [adult prompts] ≥30% reduction from baseline and Clinical Global Impression Scale–ADHD Severity score ⩽3) to open-label atomoxetine (40–100 mg/d, 12 weeks) entered a 37-week double-blind maintenance period. Patients who maintained response (double-blind atomoxetine for 12 weeks) were randomized 1:1 to atomoxetine (80–100 mg/d, n = 266) or placebo (n = 258) for 25 weeks (total duration, 1 year). Patients and investigators were blinded to response criteria and randomization timing. Change in executive function was assessed with the Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) Self-Report and Informant T scores from the randomization to the last-observation-carried-forward postrandomization week 25 (after week 17). Of the enrolled patients (n = 2017; mean age, 33.2 years; male, 58.7%), 524 responders were randomized. During open-label atomoxetine, subscales and individual items on both BRIEF-A questionnaires showed significant improvement (P < 0.001). After randomization, the following T scores improved significantly (P ⩽ 0.05) with patients in the atomoxetine group versus those in the placebo group: global executive composite, behavioral regulation, and metacognition indices; plan/organize, working memory, inhibit, task monitor and shift (both BRIEF-A questionnaires), emotional control and organization of materials (BRIEF-A Informant), and initiate (BRIEF-A Self-Report). Atomoxetine significantly improved the executive function compared with placebo, which was maintained for 25 weeks or more; the executive function of patients in the placebo group worsened but did not return to baseline levels after randomization.

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).

Sociodemographics, Comorbidities, Healthcare Utilization and Work Productivity in Japanese Patients with Adult ADHD.

Objectives This study compared the sociodemographic characteristics, comorbidities, healthcare resource utilization, and work productivity among Japanese adults who reported being diagnosed with attention-deficit/hyperactivity disorder (ADHD) to those of a non-ADHD control population. Methods Data for this study were captured from an online survey of adults in Japan conducted by Kantar Health using consumer panels. A total of 84 survey participants reported they had received a diagnosis of ADHD from a physician. Survey responses pertaining to functional status and resource utilization from this ADHD group were compared to those from a non-ADHD control group of 100 participants. Comparisons between the ADHD and non-ADHD groups were made using chi-square tests for categorical variables and t-tests for continuous variables. Results Participants in the ADHD group were on average slightly younger with a higher proportion of males. ADHD respondents reported significantly more comorbid depression, sleep difficulties, headaches, and anxiety than non-ADHD controls. Over the previous 6 months, the ADHD group made more visits to healthcare providers and the emergency room, and had more hospitalizations than non-ADHD controls. The ADHD group also rated their overall health status lower than the non-ADHD control group. Respondents with ADHD reported a significantly higher degree of health-related work impairment compared to non-ADHD, with greater absenteeism and decreased work productivity. The ADHD group indicated their symptoms negatively impacted relationships, self-esteem, and regular daily activities. Conclusions Japanese adults with ADHD face a substantial burden of illness, including lower overall health status, increased number of comorbidities, greater healthcare utilization, and significant health-related occupational impairment compared to those without ADHD. Additional research is needed to develop a better understanding of both the consequences and treatment approaches for Japanese adults with ADHD.

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.

CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial.

Atomoxetine, which is indicated for treatment of attention‐deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers. This study compared safety and tolerability among the different CYP2D6 metabolizer groups in the 12‐week open‐label phase of an atomoxetine study in adult patients with ADHD. Genotyping identified 1039 patients as extensive/ultrarapid metabolizers, 780 patients as intermediate metabolizers, and 117 patients as poor metabolizers. Common (≥5% frequency) treatment‐emergent adverse events did not significantly differ between extensive/ultrarapid and intermediate metabolizers (odds ratios were <2.0 or >0.5). Poor metabolizers had higher frequencies of dry mouth, erectile dysfunction, hyperhidrosis, insomnia, and urinary retention compared with the other metabolizer groups. There were no significant differences between extensive/ultrarapid and intermediate metabolizers in changes from baseline in vital signs. These results suggest that data from CYP2D6 intermediate and extensive/ultrarapid metabolizers can be combined when considering safety analyses related to atomoxetine.

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).