CLINICAL AND PHARMACOKINETICS EQUIVALENCE OF MULTIPLE DOSES OF LEVODOPA BENSERAZIDE GENERIC FORMULATION VERSUS THE ORIGINATOR (MADOPAR®).

BACKGROUND: While a number of generic preparations of Levodopa/carbidopa and Levodopa/benserazide 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, two-centers, randomized, double-blind, two-sequence, non-inferiority cross-over study was designed to evaluate both the PK equivalence and clinical equivalence of multiple doses of the "generic" preparation of Levodopa benserazide (LDB), Teva Italia, compared to the "originator" (Madopar®). Forty-three out-patients with a diagnosis of idiopathic Parkinson's disease (PD) on LDB, were recruited and randomly assigned to one of two study sequences: generic-originator or originator-generic. Clinical evaluations were performed at the end of each study period. A pharmacokinetic (PK) study with a LDB fixed dose (100+25 mg) was performed in a sub-population 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 three 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 AUC0-t ,t½ , Cmax, Tmax , and Clast .

CONCLUSION: These findings prove the therapeutic clinical equivalence as well the PK equivalence of the "generic" LDB and the "originator" (Madopar®).