Margherita Torti1,2, Jhessica Alessandroni3, Daniele Bravi1, Miriam Casali1, Paola Grassini1, Chiara Fossati1,4, Cristiano Ialongo5,6, Marco Onofrj7, Fabiana Giada Radicati1, Laura Vacca1,8, Stefano Bonassi9, Fabrizio Stocchi1,10. 1. Center for Parkinson's Disease, IRCCS San Raffaele Pisana, Rome, Italy. 2. San Raffaele Cassino, Rome, Italy. 3. BioBIM - Multidisciplinary Interistitutional BioBank San Raffaele Pisana -Research Center, Rome, Italy. 4. Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Piazza Lauro de Bosis 15, Rome, Italy. 5. Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Italy. 6. Department of Laboratory Medicine, Tor Vergata University of Rome, Italy. 7. Neurology Department, Università "G. D'Annunzio" di Chieti, Italy. 8. Casa di Cura Privata Policlinico (CCPP), Milan, Italy. 9. IRCCS San Raffaele Pisana, Clinical and Molecular Epidemiology Unit, Italy (Statistical Analysis) And Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy. 10. San Raffaele University, Rome, Italy.
Abstract
AIMS: While several generic preparations of levodopa/carbidopa and levodopa/benserazide (LBD) are currently available, pharmacokinetic (PK) equivalence and therapeutic equivalence studies with levodopa generics are not available in Italy. Lack of data on generic formulations is a critical factor for their limited use in this country and often lead patients to refuse the generic version of the branded drug. METHODS: An experimental, 2-centre, randomized, double-blind, 2-sequence, noninferiority cross-over study was designed to evaluate both the PK equivalence and clinical equivalence of multiple doses of the generic preparation of LDB, Teva Italia, compared to the originator (Madopar). Forty-three out-patients with a diagnosis of idiopathic Parkinson's disease on LDB, were recruited and randomly assigned to 1 of 2 study sequences: generic-originator or originator-generic. Clinical evaluations were performed at the end of each study period. A PK study with an LDB fixed dose (100 + 25 mg) was performed in a subpopulation of 14 subjects. RESULTS: Clinical data showed a reduction of 0.49 and 1.54 in the mean UPDRS III scores for the LDB and the originator, respectively. The 95% CIs [-2.21: 0.11] of the mean difference original vs LDB are smaller than the clinically significant difference of 3 UPDRS III points, supporting the conclusion that the treatment with LDB is not inferior to the originator. No statistically significant differences were found with respect to area under the curve to last dose, half-life, maximum concentration, time to maximum concentration and last observed concentration. CONCLUSION: These findings prove the therapeutic clinical equivalence as well the PK equivalence of the generic LDB and the originator (Madopar).
RCT Entities:
AIMS: While several generic preparations of levodopa/carbidopa and levodopa/benserazide (LBD) are currently available, pharmacokinetic (PK) equivalence and therapeutic equivalence studies with levodopa generics are not available in Italy. Lack of data on generic formulations is a critical factor for their limited use in this country and often lead patients to refuse the generic version of the branded drug. METHODS: An experimental, 2-centre, randomized, double-blind, 2-sequence, noninferiority cross-over study was designed to evaluate both the PK equivalence and clinical equivalence of multiple doses of the generic preparation of LDB, Teva Italia, compared to the originator (Madopar). Forty-three out-patients with a diagnosis of idiopathic Parkinson's disease on LDB, were recruited and randomly assigned to 1 of 2 study sequences: generic-originator or originator-generic. Clinical evaluations were performed at the end of each study period. A PK study with an LDB fixed dose (100 + 25 mg) was performed in a subpopulation of 14 subjects. RESULTS: Clinical data showed a reduction of 0.49 and 1.54 in the mean UPDRS III scores for the LDB and the originator, respectively. The 95% CIs [-2.21: 0.11] of the mean difference original vs LDB are smaller than the clinically significant difference of 3 UPDRS III points, supporting the conclusion that the treatment with LDB is not inferior to the originator. No statistically significant differences were found with respect to area under the curve to last dose, half-life, maximum concentration, time to maximum concentration and last observed concentration. CONCLUSION: These findings prove the therapeutic clinical equivalence as well the PK equivalence of the generic LDB and the originator (Madopar).
Authors: Guillermo A Keller; Paola Czerniuk; Roberto Bertuola; Juan G Spatz; Aria R Assefi; Guillermo Di Girolamo Journal: Clin Ther Date: 2011-04 Impact factor: 3.393