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Hisaka Igarashi,1 Mamoru Shibata,2 Akichika Ozeki,3 Kathleen Ann Day,4 Taka Matsumura3 1Department of Internal Medicine, Fujitsu Clinic, Kawasaki, Japan; 2Department of Neurology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan; 3Eli Lilly Japan K.K., Kobe, Japan; 4Eli Lilly and Company, Indianapolis, IN, USACorrespondence: Taka MatsumuraMedical Science, Medicines Development Unit Japan, Eli Lilly Japan K.K., 4-15-1 Akasaka, Akasaka Garden City 13F, Minato-ku, Tokyo, 107-0052, JapanTel +81 3 5574 9169Fax +81 3 5574 9979Email matsumura_taka@lilly.comPurpose: This study aimed to extensively evaluate the onset and maintenance effect of galcanezumab compared with placebo for the prevention of episodic migraine in Japanese patients.Patients and Methods: This was a post-hoc analysis of a Phase 2, multicenter, randomized, double-blind, placebo-controlled study conducted between December 2016 and January 2019 (ClinicalTrials.gov: NCT02959177). Patients aged between 18 and 65 years with episodic migraine were randomized to receive a monthly injection of galcanezumab (120 mg: N = 115, 240 mg: N = 114) or placebo (N = 230) for 6 months. Outcome measures included onset of effect at weekly and daily intervals—assessed by change from baseline in the number of migraine headache days and the proportion of patients with migraine headache—with galcanezumab versus placebo. To further confirm the onset and maintenance effect, the 50% response rate was also evaluated.Results: The mean change from baseline in weekly migraine headache days was significantly reduced with galcanezumab (– 0.97 days) compared with placebo (– 0.10 days) at week 1 (p ≤ 0.0001), which was maintained at all subsequent weeks up to week 4 (all p ≤ 0.0001 vs placebo). A significantly smaller proportion of galcanezumab-treated patients had migraine headache compared with placebo-treated patients at day 1 after the first injection (13.6% vs 31.4%, respectively; p ≤ 0.0001), which was also maintained at all subsequent days during the first week after the first injection. Furthermore, the 50% response rate was significantly higher with galcanezumab compared with placebo from week 1 through month 6.Conclusion: The onset of the migraine preventive effect of galcanezumab was rapid compared with placebo, starting from day 1 after the first injection in Japanese patients with episodic migraine. The effect was maintained during the first week and first month, and throughout 6 months of monthly injections of galcanezumab. Galcanezumab is a promising preventive treatment in Japanese patients with episodic migraine.Keywords: calcitonin gene-related peptide, galcanezumab, Japan, migraine disorders, onset of effect, maintenance effect

Introduction This analysis evaluated the treatment satisfaction of Japanese patients receiving galcanezumab (GMB) as a preventive medication for episodic migraine (4–14 monthly migraine headache days). Methods This phase 2, randomized, double-blind, placebo-controlled study enrolled patients aged 18–65 years at 40 centers in Japan. Patients were randomized 2:1:1 to receive monthly subcutaneous injections of placebo (PBO, n = 230), GMB 120 mg (n = 115), or GMB 240 mg (n = 114) for 6 months. Patients’ experience with treatment was measured using the Patient Global Impression of Severity (PGI-S), Patient Global Impression of Improvement (PGI-I), and Patient Satisfaction with Medication Questionnaire-Modified (PSMQ-M) scales. PGI-S was administered at baseline and months 1–6, PGI-I at months 1–6, and PSMQ-M at months 1 and 6. Prespecified analyses were differences between GMB and PBO in PGI-I and the change from baseline in PGI-S, and evaluating positive responses for the PGI-I and PSMQ-M. Results Average change ± SE from baseline across months 1–6 was − 0.09 ± 0.05 (PBO), − 0.17 ± 0.07 (GMB 120 mg, p = 0.33), and − 0.30 ± 0.07 (GMB 240 mg, p = 0.013) for PGI-S. Average PGI-I across months 1–6 was 3.39 ± 0.05 (PBO), 2.55 ± 0.07 (GMB 120 mg, p

Mamoru Shibata,1 Tomomi Nakamura,2 Akichika Ozeki,2 Kaname Ueda,2 Russell M Nichols3 1Department of Neurology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan; 2Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan; 3Global Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USACorrespondence: Tomomi NakamuraMedicines Development Unit Japan and Medical Affairs,Eli Lilly Japan K.K., 5-1-28 Isogamidori, Chuo-Ku, Kobe 651-0086, JapanTel +81-78-242-9389Email nakamura_tomomi@lilly.comPurpose: Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB).Patients and Methods: Preventive treatments for migraine have been shown to improve QoL, but few clinical trials have examined QoL outcomes in Japanese patients. This phase 2, randomized, double-blind, placebo-controlled study was conducted at 40 centers in Japan. Patients aged 18– 65 years with episodic migraine (4– 14 monthly migraine headache days) received GMB 120 mg (n=115), 240 mg (n=114), or placebo (PBO, n=230) as monthly subcutaneous injections for 6 months. QoL was measured monthly using the Migraine-Specific Quality-of-Life Questionnaire (MSQ) version 2.1. Prespecified analyses were differences between GMB and PBO for change from baseline in all 3 domains of the MSQ and MSQ-Total, for each month and the average over Months 4– 6.Results: Treatment with GMB significantly increased MSQ scores from baseline vs PBO. Average change ± SE from baseline across Months 4– 6 was 10.12± 0.72 (PBO), 17.13± 1.03 (GMB 120 mg; P< 0.001), and 15.91± 1.03 (GMB 240 mg; P< 0.001) for MSQ Role Function-Restrictive; 4.80± 0.65 (PBO), 9.64± 0.93 (GMB 120 mg; P< 0.001), and 8.35± 0.93 (GMB 240 mg; P< 0.05) for MSQ Role Function-Preventive (MSQ-RFP); 3.46± 0.77 (PBO), 10.04± 1.10 (GMB 120 mg; P< 0.001), and 7.73± 1.10 (GMB 240 mg; P< 0.05) for MSQ Emotional Function, and 7.14± 0.67 (PBO), 13.46± 0.95 (GMB 120 mg; P< 0.001), and 11.98± 0.95 (GMB 240 mg; P< 0.001) for MSQ-Total. Significantly greater improvement in scores in all MSQ domains and MSQ-Total was observed for both GMB doses vs PBO at Month 1 and was maintained for Months 1– 6 (excluding Month 5 for MSQ-RFP).Conclusion: Preventive treatment with GMB 120 mg/240 mg improves MSQ scores in Japanese patients with episodic migraine. Improvements were seen within the first month and maintained for 6 months and are similar to those seen in global studies enrolling primarily Caucasian patients.Clinical Trial Registration: ClinicalTrials.gov, NCT02959177 (registered November 7, 2016).Keywords: MeSH: preventive therapy, quality of life

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.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.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.Long-term treatment with 120-mg or 240-mg galcanezumab was safe and effective in Japanese patients with EM or CM.https://clinicaltrials.gov, identifier: NCT02959190.

Objectives To determine whether early changes in International Prostate Symptom Score predict final improvement in the quality of life and treatment satisfaction of patients with lower urinary tract symptoms from benign prostatic hyperplasia receiving tadalafil. Methods This post-hoc analysis of three randomized-controlled trials of tadalafil for lower urinary tract symptoms from benign prostatic hyperplasia used subpopulations based on treatment status (tadalafil, placebo) and region (Japan, Asia). Logistic regression, principal component analysis and hierarchical clustering analysis were applied to individual International Prostate Symptom Score and Patient Global Impression of Improvement response scores. Results From logistic regression, most individual International Prostate Symptom Score items predicted either International Prostate Symptom Score remitter or responder status; only International Prostate Symptom Score Quality of Life predicted Patient Global Impression of Improvement responder status in tadalafil-treated patients. Among tadalafil-treated patients, principal component analysis showewd that improvement of International Prostate Symptom Score items 2, 4, 7 and International Prostate Symptom Score Quality of Life at early visits were associated with Patient Global Impression of Improvement (final visit), whereas International Prostate Symptom Score items 1, 3, 5 and 6 at early visits were associated with total International Prostate Symptom Score at the final visit. No clear predictive items for Patient Global Impression of Improvement and total International Prostate Symptom Score existed for placebo-treated patients. Hierarchical clustering analysis showed that the closest association was between International Prostate Symptom Score Quality of Life and International Prostate Symptom Score item 7 in placebo- and tadalafil-treated patients, which supports the principal component analysis results. Conclusions Early changes of storage and voiding symptoms by tadalafil might lead to treatment satisfaction and overall International Prostate Symptom Score improvement, respectively. This finding could help physicians predict tadalafil treatment outcomes for patients with lower urinary tract symptoms from benign prostatic hyperplasia.

Objective:This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine.Methods:In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S).Results:The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p < 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo.Conclusion:The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

The goal of this study was to assess the safety and efficacy of 0.75 mg of dulaglutide, a once weekly glucagon-like peptide-1 receptor agonist, in Japanese patients with type 2 diabetes (T2D) on a single oral hypoglycemic agent (OHA). In this phase 3, nonrandomized, open-label, parallel-group, 52-week study, safety and efficacy of once weekly dulaglutide 0.75 mg were assessed in Japanese patients with T2D on a single OHA (sulfonylureas [SU], biguanides [BG], α-glucosidase inhibitors [AGI], thiazolidinedione [TZD], or glinides [GLN]). A total of 394 patients were treated with study drug, and 92.9% completed the 52-week treatment period. The most frequent treatment-emergent adverse events were nasopharyngitis and gastrointestinal disorders, including constipation, diarrhea, and nausea. Incidences of hypoglycemia varied across the combination therapy groups: incidence was greater in patients receiving SU compared with other combinations. No severe hypoglycemic episodes occurred during the study. Increases from baseline in pancreatic and total amylase, lipase, and pulse rate were observed in all 5 combination therapy groups. Significant reductions from baseline in HbA1c were observed in all 5 combination therapy groups (-1.57% to -1.69%, p < 0.001 for all). Mean body weight changes from baseline varied across the combination therapy groups: a significant increase was observed in combination with TZD, there were no significant changes in combination with SU or GLN, and significant reductions were observed in combination with BG or AGI. Once weekly dulaglutide 0.75 mg in combination with a single OHA was overall well tolerated and improved glycemic control in Japanese patients with T2D.

BackgroundIn the treatment of major depressive disorder (MDD), it is not fully understood how individual symptoms improve over time (trajectory) in remitters. This study compared symptom improvement trajectories, as measured with the 17-item Hamilton Depression Rating Scale (HAM-D17), in remitters and nonremitters.MethodsThis analysis is based on 10 placebo-controlled, randomized, double-blind trials of duloxetine (40–60mg/day) for treatment of MDD from baseline up to week 8. Remission was defined as a HAM-D17 total score ≤7 at week 8 (last observation carried forward). Trajectories of HAM-D17 items were assessed by mixed model repeated measures analysis for treatment and remitter-nonremitter comparisons. Grouping of the trajectories was performed by factor analysis. Predictor analysis using HAM-D17 items was conducted by logistic regression.ResultsThere were 1555 patients in the duloxetine group (489 [31.4%] remitters) and 1206 patients in the placebo group (290 [24.0%] remitters; P