Comparative bioavailability Fifteen Bioavailability studies are listed in the dossier. Fourteen of these relate to the Viekira Pak components and have been reviewed in the separate parallel evaluation for Viekira Pak. The remaining study (Study M14-356) is a comparative bioavailability study between the proposed ribavirin 600 mg tablets and 3 x 200 mg Copegus ribavirin tablets. The study demonstrated bioequivalent of the two treatments because the 90% confidence intervals for Cmax and AUC0-t ratios fell within the normal bioequivalence range (0.80 to 1.25). A justification for not providing biostudies for the 200 mg and 400 mg tablets was provided and this is considered acceptable with respect to CMC aspects. Quality summary and conclusions Registration of the proposed Viekira Pak-RBV combination therapy composite pack, consisting of the following components: a new fixed-dose combination film coated tablet comprising of 75 mg paritaprevir, 50 mg ritonavir and 12.5 mg ombitasvir, and dasabuvir (as sodium salt) 250 mg film coated tablets, ribavirin 200 mg, 400 mg and/or 600 mg film coated tablets is recommended with respect to quality and biopharmaceutic aspects. All issues raised during the initial evaluation of this application have now been satisfactorily resolved apart from some minor PI and labelling revisions. As no significant pharmaceutical chemistry issues were identified, the CMC aspects of the submission were not referred to the Pharmaceutical Subcommittee of the ACPM, in keeping with recent branch policy. III. Nonclinical findings Introduction The nonclinical evaluation of this submission has been performed in four parts the first three for each of the new chemical entities and the third for the combination product; Paritaprevir Ombitasvir Dasabuvir Fixed dose combination Each of these will be presented separately below.
Comparative bioavailability Fifteen Bioavailability studies are listed in the dossier. Fourteen of these relate to the Viekira Pak components and have been reviewed in the separate parallel evaluation for Viekira Pak. The remaining study (Study M14-356) is a comparative bioavailability study between the proposed ribavirin 600 mg tablets and 3 x 200 mg Copegus ribavirin tablets. The study demonstrated bioequivalent of the two treatments because the 90% confidence intervals for Cmax and AUC0-t ratios fell within the normal bioequivalence range (0.80 to 1.25). A justification for not providing biostudies for the 200 mg and 400 mg tablets was provided and this is considered acceptable with respect to CMC aspects. Quality summary and conclusions Registration of the proposed Viekira Pak-RBV combination therapy composite pack, consisting of the following components: a new fixed-dose combination film coated tablet comprising of 75 mg paritaprevir, 50 mg ritonavir and 12.5 mg ombitasvir, and dasabuvir (as sodium salt) 250 mg film coated tablets, ribavirin 200 mg, 400 mg and/or 600 mg film coated tablets is recommended with respect to quality and biopharmaceutic aspects. All issues raised during the initial evaluation of this application have now been satisfactorily resolved apart from some minor PI and labelling revisions. As no significant pharmaceutical chemistry issues were identified, the CMC aspects of the submission were not referred to the Pharmaceutical Subcommittee of the ACPM, in keeping with recent branch policy. III. Nonclinical findings Introduction The nonclinical evaluation of this submission has been performed in four parts the first three for each of the new chemical entities and the third for the combination product; Paritaprevir Ombitasvir Dasabuvir Fixed dose combination Each of these will be presented separately below.
auspar-paritaprevir-ritonavir-ombitasvir-dasabuvir-as-sodium-salt-and-ribavirin-170324.docx