N0v 2005 Open, randomized, single- dose, 3-period Cholestyramine for 5d (D6 through D10) of each B: 25 – Apr 2006 crossover, 3- sequence study with a 21d washout period C: 26 between doses of teriflunomide. Healthy BEQ10169 Determine bioequivalence of teriflunomide 7 and Teriflunomide test tablets 94/84 * 14mg test tablets and teriflunomide 7 and 14mg 7 and 14mg tablets without colloidal silica 60M/34F 1 centre reference tablets, respectively Single doses of 7mg (Group 1) or 14mg (Group 2) Grp 1: 27.8 ± UK randomized, single-dose, 2-treatment by on Dl 6.0 (19-44)y; Feb Jun 2007 crossover study performed in 2 parallel fasting Grp 2: 27.2 ± – groups, with a 32d washout Cholestyramine for 3d(D27 through D29) 6.4 (18-45)y Between doses of teriflunomide Grp 1: 47; Grp 2: 47 Healthy *[Information redacted] In vitro studies The in human biomaterials studies for teriflunomide evaluated its potential interaction with p-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) (Study AIV0202), its transport in hepatocytes (Study TRE0034), its protein binding (Studies HMR008477, HMR010274, HMR015182, HMR014543), its hepatic metabolism (Studies DMPK/USA/2005-0050, HMR14997, HMR017949, MIH0794), its effect on uric acid renal transport (DIV1516) and its potential for non-metabolic-based drug-drug interactions (Study TRE0029) or metabolic-based drug-drug interactions (Studies DMPK/USA/2005-0097, MIH0376, MIH0542, MIH0793, MIH0882, MIH0318). 2 In vitro studies 14C-teriflunomide metabolism
N0v 2005 – Apr 2006 Open, randomized, single- dose, 3-period crossover, 3- sequence study with a 21d washout between doses of teriflunomide. Cholestyramine for 5d (D6 through D10) of each period B: 25 C: 26 Healthy BEQ10169 * 1 centre UK Feb – Jun 2007 Determine bioequivalence of teriflunomide 7 and 14mg test tablets and teriflunomide 7 and 14mg reference tablets, respectively randomized, single-dose, 2-treatment by crossover study performed in 2 parallel groups, with a 32d washout Between doses of teriflunomide Teriflunomide test tablets 7 and 14mg tablets without colloidal silica Single doses of 7mg (Group 1) or 14mg (Group 2) on Dl fasting Cholestyramine for 3d(D27 through D29) 94/84 60M/34F Grp 1: 27.8 ± 6.0 (19-44)y; Grp 2: 27.2 ± 6.4 (18-45)y Grp 1: 47; Grp 2: 47 Healthy *[Information redacted] In vitro studies The in human biomaterials studies for teriflunomide evaluated its potential interaction with p-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) (Study AIV0202), its transport in hepatocytes (Study TRE0034), its protein binding (Studies HMR008477, HMR010274, HMR015182, HMR014543), its hepatic metabolism (Studies DMPK/USA/2005-0050, HMR14997, HMR017949, MIH0794), its effect on uric acid renal transport (DIV1516) and its potential for non-metabolic-based drug-drug interactions (Study TRE0029) or metabolic-based drug-drug interactions (Studies DMPK/USA/2005-0097, MIH0376, MIH0542, MIH0793, MIH0882, MIH0318). 2 In vitro studies 14C-teriflunomide metabolism
auspar-teriflunomide-130521-cer.docx