USA Single dose of 70mg (50 µCi) on Dl after an 31.2 ± 9.89 (21 overnight fast —47)y Jun Jul 2005 – Cholestyramine for 7 d (D22 to D28) Healthy TDR10892 Assess tolerability, safety, and PK parameters Teriflunomide 14mg tablets 13/4 repeated oral doses of teriflunomide 70mg * 70mg (5 tablets) QD for 14 d (Dl through D14) 6M/7F Randomized, double-blind, placebo-controlled, 1 centre Placebo (5 tablets) QD for 14 d (Dl through D14) 48.8 ± 13.6 day repeated dose study France Cholestyramine for 13d (D15 to 27) teriflunomide: 10 placebo: 3 Healthy Bioavailability Study Reports 1002 To assess the effect of food on bioavailability of Teriflunomide 20-mg tablets single dose 16/14 teriflunomide 20mg * Period1: loading dose of 20mg on Day l under, 16M Open-label, randomized, 4-period, 2-treatment fasted conditions 1 centre 48 ± 8.1 (40 — crossover study with 7d washout between 2 Periods 2 and 3:20mg under fasted conditions on 65)y Germany treatment administrations either Day18 or 38 and 20mg under fed conditions Healthy July - Nov 2000 (15 mm after high-fat meal) on either Day 18 or 38 Period 4 Oral Cholestyramine for 9d – ALI6504 To assess effect of food on bioavailability of Teriflunomide:7-and 14mg tablets in fed (high- fat 30/26 teriflunomide 7 and 14mg tablets breakfast) or fasted conditions
USA Jun – Jul 2005 Single dose of 70mg (50 µCi) on Dl after an overnight fast Cholestyramine for 7 d (D22 to D28) 31.2 ± 9.89 (21 —47)y Healthy TDR10892 * 1 centre France Assess tolerability, safety, and PK parameters repeated oral doses of teriflunomide 70mg Randomized, double-blind, placebo-controlled, repeated dose study Teriflunomide 14mg tablets 70mg (5 tablets) QD for 14 d (Dl through D14) Placebo (5 tablets) QD for 14 d (Dl through D14) Cholestyramine for 13d (D15 to 27) 13/4 6M/7F 48.8 ± 13.6 teriflunomide: 10 placebo: 3 Healthy Bioavailability Study Reports 1002 * 1 centre Germany July - Nov 2000 To assess the effect of food on bioavailability of teriflunomide 20mg Open-label, randomized, 4-period, 2-treatment crossover study with 7d washout between 2 treatment administrations Teriflunomide 20-mg tablets single dose Period1: loading dose of 20mg on Day l under, fasted conditions Periods 2 and 3:20mg under fasted conditions on either Day18 or 38 and 20mg under fed conditions (15 mm after high-fat meal) on either Day 18 or 38 Period 4 – Oral Cholestyramine for 9d 16/14 16M 48 ± 8.1 (40 — 65)y Healthy ALI6504 To assess effect of food on bioavailability of teriflunomide 7 and 14mg tablets Teriflunomide:7-and 14mg tablets in fed (high- fat breakfast) or fasted conditions 30/26 day
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