Efficacy and Safety of Valbenazine in Japanese Patients With Tardive Dyskinesia and Schizophrenia/Schizoaffective Disorder or Bipolar Disorder/Depressive Disorder: Primary Results and Post Hoc Analyses of the J-KINECT Study.

PURPOSE: This post hoc analysis investigated whether a patient's underlying psychiatric disease (schizophrenia/schizoaffective disorder [SCHZ] or bipolar disorder/depressive disorder [MOOD]) influenced the efficacy or safety of valbenazine for tardive dyskinesia (TD) in an Asian population. METHODS: We analyzed data from J-KINECT, a multicenter, phase II/III, randomized, double-blind study, which consisted of a 6-week placebo-controlled period followed by a 42-week extension where Japanese patients with TD received once-daily 40- or 80-mg valbenazine. We compared the change from baseline in Abnormal Involuntary Movement Scale total score and Clinical Global Impression of TD score between patients with SCHZ and those with MOOD, and incidence of treatment-emergent adverse events. RESULTS: Of 256 patients included in the placebo-controlled period, 211 continued to the long-term extension. The mean change from baseline in Abnormal Involuntary Movement Scale total score at week 6 (95% confidence interval) was -1.8 (-3.2 to -0.5) and -3.3 (-4.7 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (SCHZ group), and -2.4 (-3.9 to -0.9) and -3.5 (-5.1 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (MOOD group), demonstrating improvement at either dose level over placebo, regardless of the underlying disease. These results were maintained to week 48, and improvements of Clinical Global Impression of TD scores were similar. There were no notable differences in the incidence of serious or fatal treatment-emergent adverse events by underlying disease; differences in the incidence of worsening schizophrenia and depression were attributed to underlying disease progression. CONCLUSIONS: Safety and efficacy of long-term valbenazine therapy for TD did not vary according to underlying psychiatric disease.

Correction: Infliximab for pediatric patients with Crohn's disease: A Phase 3, open-label, uncontrolled, multicenter trial in Japan.

[This corrects the article DOI: 10.1371/journal.pone.0201956.].

Infliximab for pediatric patients with ulcerative colitis: a phase 3, open-label, uncontrolled, multicenter trial in Japan.

BACKGROUND: Pediatric ulcerative colitis (UC) is typically more extensive and has a more active disease course than adult UC, and requires early treatment augmentation to achieve and maintain disease remission. The present study aimed to investigate the efficacy, safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients with moderate-to-severe UC and inadequate response to existing treatment. METHODS: This open-label, uncontrolled, multicenter, Phase 3 trial was conducted at 17 centers in Japan between April 2012 and September 2014. Pediatric patients (aged 6-17 years) diagnosed with moderate-to-severe UC received a treatment protocol comprising 5 mg/kg IFX at Weeks 0, 2, and 6, and Clinical Activity Index (CAI)-based responders at Week 8 also received treatment at 8-week intervals at Weeks 14 and 22, with a final evaluation at Week 30. RESULTS: A total of 21 patients were treated in this study. IFX therapy rapidly improved clinical symptoms, and this effect was maintained for up to 30 weeks. Overall CAI-based remission rate was 42.9% and overall Pediatric Ulcerative Colitis Activity Index (PUCAI)-based remission rate was 19.0%. Median partial Mayo score was 6.0 at baseline and 4.0 at Week 30 (overall). Among the eight patients who underwent sigmoidoscopy, Mayo response was achieved at Week 30 (overall) in three patients (37.5%). Trough serum IFX concentrations in Week 8 CAI-based responders were maintained throughout the study period. Adverse events and serious adverse events were observed in 95.2 and 14.3% of patients, respectively. CONCLUSIONS: These results support the use of IFX in the treatment of pediatric patients with UC with inadequate response to existing treatment. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT01585155 .

Infliximab for pediatric patients with Crohn's disease: A Phase 3, open-label, uncontrolled, multicenter trial in Japan.

OBJECTIVES: The prevalence of pediatric Crohn's disease (CD) is increasing in Japan and other countries, and many patients are unresponsive to or do not tolerate current treatment options. This study aimed to investigate the efficacy, safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients with moderate-to-severe CD and inadequate response to existing treatment. STUDY DESIGN: This was an open-label, uncontrolled, multicenter Phase 3 study conducted at nine sites in Japan between April 2012 and March 2015. Pediatric patients (aged 6-17 years) with moderate-to-severe CD were treated with IFX 5 mg/kg at Weeks 0, 2, and 6, and at 8-week intervals thereafter until Week 46, with final evaluation at Week 54. IFX dose was increased to 10 mg/kg in patients who showed loss of response to IFX from Week 14 onwards. RESULTS: A total of 14 patients fulfilled eligibility criteria and were treated. Dose-escalation criteria were met by five patients who then received 10 mg/kg IFX. The remaining nine patients continued to receive an IFX dose of 5 mg/kg. IFX rapidly improved clinical symptoms and its effect was maintained for up to 54 weeks. Overall Pediatric Crohn's Disease Activity Index (PCDAI) response rate was 85.7%, and overall PCDAI remission rate was 64.3%. Three out of five patients who increased IFX dose regained PCDAI remission by retrieval of serum IFX concentration. Adverse events and serious adverse events occurred in 100.0% and 14.3% of patients, respectively. There was no substantial difference in the safety profiles of patients taking a constant dose of 5 mg/kg and those taking an increased dose of 10 mg/kg. CONCLUSIONS: These findings support the effective use of IFX in the treatment of pediatric patients with CD where other treatments have proven ineffective.