Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To p...Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To preliminarily evaluate the efficacy and safety of GW117 in major depressive disorder(MDD)and to explore the optimal dosing.Methods A total of 280 eligible patients aged 18-65years with MDD were randomly assigned(1:1:1:1)to8 weeks of double-blind treatment with fixed doses of GW117 tablets(20,40,60 mg/day)or placebo.The primary endpoint was the change from baseline to Week 8 in the total score of the Hamilton Rating Scale for Depression-17item(HAMD-17).Key secondary endpoints included changes in the Montgomery-?sberg Depression Rating Scale(MADRS)total score over the same period.Results In the full analysis set(n=276),GW117 showed numerically greater reductions versus placebo in the HAMD-17 and MADRS total scores,as well as higher response rates at Week 8.However,these differences did not reach statistical significance,potentially due to a high placebo response and other contributing factors.In a post hoc analysis of an optimal subgroup(baseline HAMD-17>24 or insomnia factor>4),GW117 showed efficacy in improving multidimensional symptoms,including insomnia.The 20 mg dose demonstrated a significant3.66-point greater reduction in MADRS(p=0.026)and a23.16%higher response rate(p=0.013)compared with placebo.GW117 was well-tolerated,with no cases of alanine aminotransferase or aspartate aminotransferase exceeding 3×the upper limit of normal and no concerning safety signals reported.Conclusions This exploratory study found that GW117demonstrated encouraging antidepressant efficacy and a favourable safety profile in patients with MDD.Although differences versus placebo did not reach statistical significance in the overall population,GW11720 mg monotherapy showed significant improvements in multidimensional depressive symptoms,including insomnia,in the optimal response subgroup.No hepatotoxicity was reported,supporting its promising therapeutic potential for further clinical development.展开更多
Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving va...Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.展开更多
文摘Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To preliminarily evaluate the efficacy and safety of GW117 in major depressive disorder(MDD)and to explore the optimal dosing.Methods A total of 280 eligible patients aged 18-65years with MDD were randomly assigned(1:1:1:1)to8 weeks of double-blind treatment with fixed doses of GW117 tablets(20,40,60 mg/day)or placebo.The primary endpoint was the change from baseline to Week 8 in the total score of the Hamilton Rating Scale for Depression-17item(HAMD-17).Key secondary endpoints included changes in the Montgomery-?sberg Depression Rating Scale(MADRS)total score over the same period.Results In the full analysis set(n=276),GW117 showed numerically greater reductions versus placebo in the HAMD-17 and MADRS total scores,as well as higher response rates at Week 8.However,these differences did not reach statistical significance,potentially due to a high placebo response and other contributing factors.In a post hoc analysis of an optimal subgroup(baseline HAMD-17>24 or insomnia factor>4),GW117 showed efficacy in improving multidimensional symptoms,including insomnia.The 20 mg dose demonstrated a significant3.66-point greater reduction in MADRS(p=0.026)and a23.16%higher response rate(p=0.013)compared with placebo.GW117 was well-tolerated,with no cases of alanine aminotransferase or aspartate aminotransferase exceeding 3×the upper limit of normal and no concerning safety signals reported.Conclusions This exploratory study found that GW117demonstrated encouraging antidepressant efficacy and a favourable safety profile in patients with MDD.Although differences versus placebo did not reach statistical significance in the overall population,GW11720 mg monotherapy showed significant improvements in multidimensional depressive symptoms,including insomnia,in the optimal response subgroup.No hepatotoxicity was reported,supporting its promising therapeutic potential for further clinical development.
基金sub-project of National Major Scientific and Technological Special Project of China for‘Significant New Drugs Development’[2015ZX09501008-004]。
文摘Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.
