A long-term open-label safety study of galcanezumab in Japanese patients with migraine.

BACKGROUND: Because of the burden of migraine in Japan, there is a need for safe and effective preventive treatments. This study assessed the long-term safety and tolerability of galcanezumab in Japanese patients with episodic (EM) or chronic (CM) migraine. RESEARCH DESIGN AND METHODS: In this 12-month open-label study, adult patients with EM who previously completed a 6-month, double-blind, placebo-controlled trial were newly randomized to either galcanezumab dose from placebo or continued their assigned galcanezumab doses (all: 120 mg, n = 120; 240 mg, n = 126). Newly enrolled patients with CM were randomized to 120-mg (n = 32) or 240-mg (n = 33) galcanezumab. The primary outcome was long-term safety and tolerability. RESULTS: The incidence of TEAEs was similar between treatment groups. Nasopharyngitis was the most common TEAE, followed by injection site reactions. The discontinuation rate was low (EM = 9.3%; CM = 15.4%) and no deaths were reported. Patients with EM who received galcanezumab in the placebo-controlled trial had sustained efficacy. Both doses reduced the number of migraine headache days in patients with CM. CONCLUSIONS: Long-term treatment with 120-mg or 240-mg galcanezumab was safe and effective in Japanese patients with EM or CM. TRIAL REGISTRATION: https://clinicaltrials.gov, identifier: NCT02959190.

Real-World Safety and Effectiveness of Tadalafil in Patients with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Japanese Post-Marketing Surveillance Study.

OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia in real-world clinical practice; and to investigate the safety profile in patients aged ≥75 years. PATIENTS AND METHODS: This was a prospective, non-interventional, multicenter, post-marketing surveillance study in which Japanese patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia were observed for up to 18 months after initiating tadalafil treatment. The real-world safety and effectiveness outcomes were assessed at baseline and at 1, 3, 6, 12, and 18 months post-treatment or the last day of treatment. RESULTS: Most patients received tadalafil 5 mg per day throughout the observation period. Among 1393 patients analyzed for safety, the overall incidence of adverse drug reactions was 8.3%. These adverse drug reactions were generally consistent with the known safety profile of tadalafil and no new safety risks were identified in long-term use. There was no statistical difference in the frequency of adverse drug reactions between patients aged <75 and ≥75 years. The mean change in total International Prostate Symptom Score (IPSS) and IPSS-quality of life subscore was significantly improved at each timepoint. At 18 months, IPSS had improved by 5.0 points (P < 0.001) and IPSS-quality of life subscore had improved by 1.5 points (P < 0.001). The mean change in post-voiding residual urine volume from baseline was significant at each time point and was -9.8 mL at 18 months (P < 0.001); there were no significant differences from baseline in maximum urinary flow rate. CONCLUSION: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. In addition, safety profiles in patients aged ≥75 years were similar to patients aged <75 years.

Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance.

OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. METHODS: This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. RESULTS: The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. CONCLUSION: This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. METHODS: This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. RESULTS: Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. CONCLUSION: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.