Cocktail: 2d Cocktail + teriflunomide: 34 INT11932 Assess effect of repeated oral doses of Initially given buprion150mg tablet single dose on 17/17 teriflunomide on PKs of bupropion (CYP2B6 P1, D 1 * 17M probe). Assess teriflunomide trough plasma Then(P2 only) teriflunomide (14mg tablets) 70mg 1 centre 32.4 ± 7.1 (23 - concentrations (Ctrough). Assess clinical and single dose QD for 4d followed by 14mg QD for 44)y laboratory safety of teriflunomide co-administered USA 10d, 12th dose of teriflunomide given 30 min with bupropion. A single-centre, open-label, Bupropion before bupropion 150-mg tablet Feb May – nonrandomized, single-sequence, 2-treatment, 2- 17 2011 period study with a minimum 3-day washout Teriflunomide following single oral administration in Period 1 alone: 17 Bupropion + teriflunomide: 17 Healthy INTl1697 Assess effect of repeated doses of teriflunomide on Teriflunomide 14mg tablet 20/18 PK of a single dose of repaglinide. * Loading dose of 70mg (5 tablets) QD for 4d 20M Open-label, nonrandomized, 2-period, 2-treatment, followed by 14mg (1 tablet) QD for 8d (P2 only); 1 centre 31.8 ± 5.8 (21 - single sequence study 12th dose given 30 mm before repaglinide 44)y USA In fed conditions except when co administered Teriflunomide: Jan Apr 2011 with repaglinide – 20
Cocktail: 2d Cocktail + teriflunomide: 34 INT11932 * 1 centre USA Feb – May 2011 Assess effect of repeated oral doses of teriflunomide on PKs of bupropion (CYP2B6 probe). Assess teriflunomide trough plasma concentrations (Ctrough). Assess clinical and laboratory safety of teriflunomide co-administered with bupropion. A single-centre, open-label, nonrandomized, single-sequence, 2-treatment, 2- period study with a minimum 3-day washout following single oral administration in Period 1 Initially given buprion150mg tablet single dose on P1, D 1 Then(P2 only) teriflunomide (14mg tablets) 70mg single dose QD for 4d followed by 14mg QD for 10d, 12th dose of teriflunomide given 30 min before bupropion 150-mg tablet 17/17 17M 32.4 ± 7.1 (23 - 44)y Bupropion 17 Teriflunomide alone: 17 Bupropion + teriflunomide: 17 Healthy INTl1697 * 1 centre USA Jan – Apr 2011 Assess effect of repeated doses of teriflunomide on PK of a single dose of repaglinide. Open-label, nonrandomized, 2-period, 2-treatment, single sequence study Teriflunomide 14mg tablet Loading dose of 70mg (5 tablets) QD for 4d followed by 14mg (1 tablet) QD for 8d (P2 only); 12th dose given 30 mm before repaglinide In fed conditions except when co administered with repaglinide 20/18 20M 31.8 ± 5.8 (21 - 44)y Teriflunomide: 20
auspar-teriflunomide-130521-cer.docx