The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform
Renato Mantegazza - One of the best experts on this subject based on the ideXlab platform.
-
Amifampridine tablets for the treatment of lambert eaton myasthenic syndrome
Expert Review of Clinical Pharmacology, 2019Co-Authors: Renato MantegazzaAbstract:Introduction: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting in muscle weakness and fatigability. Diagnostic features are specific neurophysiological alterations and autoantibody detection. The present review is focused on the use of Amifampridine Phosphate to treat LEMS patients.Areas covered: Medline search from 1990 to 2019 was examined using the free subject terms: Lambert-Eaton myasthenic syndrome, LEMS, Amifampridine, 3,4-diaminopyridine, which were then combined with Treatment, Therapy, Clinical Trial, Controlled Clinical Trial, Randomized Clinical Trial and Cochrane Review. The author has done a supervised analysis of the retrieved articles and focused on those subjectively evaluated as most relevant.Expert commentary: Data from randomized clinical trials and case series have demonstrated that Lambert-Eaton myasthenic syndrome symptoms were successfully treated by Amifampridine Phosphate. Hence, the drug represents a substantial step forward in the symptomatic treatment of the disease due to its efficacy, safety and reliable GMP formulation. As Amifampridine Phosphate works by enhancing the release of acetylcholine at the neuromuscular junction by blocking K+ efflux at the pre-synaptic membrane, it is also conceivable to use it for other diseases of the neuromuscular junction in which such an effect is searched for.
-
Amifampridine phosphate in the treatment of muscle specific kinase myasthenia gravis a phase iib randomized double blind placebo controlled double crossover study
Sage Open Medicine, 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective:The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Qua...
-
Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study
'SAGE Publications', 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective: The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only Amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–Amifampridine–placebo sequence and three patients to receive Amifampridine–placebo–Amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p
-
lambert eaton myasthenic syndrome lems a rare autoimmune presynaptic disorder often associated with cancer
Journal of Neurology, 2017Co-Authors: Benedikt Schoser, B Eymard, Joe Datt, Renato MantegazzaAbstract:Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder that is related to the loss of functional P/Q-type voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals. Up to 60% of cases occur as a paraneoplastic disorder (SCLC-LEMS), most commonly in association with small cell lung cancer. The remaining cases have an idiopathic non-tumor etiology but are associated with underlying autoimmune disease (NT-LEMS). Patients with LEMS invariably experience progressive proximal muscle weakness, often accompanied by general fatigue and autonomic symptoms. Some LEMS clinical symptoms overlap with those of other myasthenic syndromes, most commonly myasthenia gravis, which can contribute to misdiagnosis or delayed diagnosis. Prognosis is related to the presence of cancer or autoimmune disease and the severity/distribution of muscle weakness. Cause of death in patients with SCLC-LEMS is typically tumor progression, whereas NT-LEMS does not reduce life expectancy. LEMS diagnosis is supported by a threefold approach: clinical features, electromyography, and anti-VGCC antibody serology. LEMS is a clinically important early indicator of possible cancer; therefore, a LEMS diagnosis should immediately prompt rigorous oncological screening and surveillance. Symptomatic treatment of LEMS typically involves medications that improve neurotransmission (e.g., the potassium channel blocker Amifampridine [3,4-diaminopyridine]), with addition of immunosuppressants/modulators (e.g., prednisone plus azathioprine) in individuals with persistent symptoms. Where a tumor is identified, oncological treatment should take priority. It should be remembered, however, that LEMS has a significant impact on a patient’s quality of life and ability to perform daily activities, and therefore warrants timely diagnosis and appropriate treatment in and of itself.
Silvia Bonanno - One of the best experts on this subject based on the ideXlab platform.
-
Amifampridine phosphate in the treatment of muscle specific kinase myasthenia gravis a phase iib randomized double blind placebo controlled double crossover study
Sage Open Medicine, 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective:The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Qua...
-
Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study
'SAGE Publications', 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective: The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only Amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–Amifampridine–placebo sequence and three patients to receive Amifampridine–placebo–Amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p
Angela Campanella - One of the best experts on this subject based on the ideXlab platform.
-
Amifampridine phosphate in the treatment of muscle specific kinase myasthenia gravis a phase iib randomized double blind placebo controlled double crossover study
Sage Open Medicine, 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective:The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Qua...
-
Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study
'SAGE Publications', 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective: The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only Amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–Amifampridine–placebo sequence and three patients to receive Amifampridine–placebo–Amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p
Lorenzo Cottini - One of the best experts on this subject based on the ideXlab platform.
-
Amifampridine phosphate in the treatment of muscle specific kinase myasthenia gravis a phase iib randomized double blind placebo controlled double crossover study
Sage Open Medicine, 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective:The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Qua...
-
Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study
'SAGE Publications', 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective: The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only Amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–Amifampridine–placebo sequence and three patients to receive Amifampridine–placebo–Amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p
Greta Brenna - One of the best experts on this subject based on the ideXlab platform.
-
Amifampridine phosphate in the treatment of muscle specific kinase myasthenia gravis a phase iib randomized double blind placebo controlled double crossover study
Sage Open Medicine, 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective:The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Qua...
-
Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study
'SAGE Publications', 2018Co-Authors: Silvia Bonanno, Maria Barbara Pasanisi, Rita Frangiamore, Lorenzo Maggi, Carlo Antozzi, Francesca Andreetta, Angela Campanella, Greta Brenna, Lorenzo Cottini, Renato MantegazzaAbstract:Objective: The aim of this study is to determine the safety and the efficacy of Amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which Amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–Amifampridine–placebo sequence or Amifampridine–placebo–Amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only Amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–Amifampridine–placebo sequence and three patients to receive Amifampridine–placebo–Amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p