Repaglinide 0.5mg tablet, halved Teriflunomide + repaglinide: 0.25mg (1/2 tablet) single dose on P1, Dl and P2, D12 Repaglinide: 20 In fasted conditions Healthy Cholestyramine for 11d Teriflunomide: 12d Repaglinide: 2d INT6040 Assess effect of repeated daily oral doses of Teriflunomide 14mg tablets 14/12 teriflunomide on PD and PK profile of warfarin * Loading dose of 70mg QD for first3d of P2, 14M after a single oral dose of 25mg warfarin; assess followed by 14mg QD for 8 consecutive days 1 centre 31.0 ± 9.0 (19 - safety of teriflunomide co administered with Warfarin 5mg tablets 45) warfarin compared to warfarin alone UK Single dose of 25mg (5 tablets) on P1, Dl and on P1: 14 Open, nonrandomized, single sequence, 2- Feb Jul 2007 – P2, D5 (warfarin); treatment, 2-period Cholestyramine for 11d (D12 to D22) P2: 12 (warfarin + Teriflunomide: 11d teriflunomide) Warfarin: 2d Healthy INT10563 Assess effect of 14-day repeated oral doses of Teriflunomide 14mg tablets 26/23 teriflunomide on PK of midazolam, as a probe * 70mg (5 tablets) QD 3d followed by 14mg 26M substrate for CYP3A activity. maintenance dose QD 11d
Repaglinide 0.5mg tablet, halved 0.25mg (1/2 tablet) single dose on P1, Dl and P2, D12 In fasted conditions Cholestyramine for 11d Teriflunomide: 12d Repaglinide: 2d Teriflunomide + repaglinide: Repaglinide: 20 Healthy INT6040 * 1 centre UK Feb – Jul 2007 Assess effect of repeated daily oral doses of teriflunomide on PD and PK profile of warfarin after a single oral dose of 25mg warfarin; assess safety of teriflunomide co administered with warfarin compared to warfarin alone Open, nonrandomized, single sequence, 2- treatment, 2-period Teriflunomide 14mg tablets Loading dose of 70mg QD for first3d of P2, followed by 14mg QD for 8 consecutive days Warfarin 5mg tablets Single dose of 25mg (5 tablets) on P1, Dl and on P2, D5 Cholestyramine for 11d (D12 to D22) Teriflunomide: 11d Warfarin: 2d 14/12 14M 31.0 ± 9.0 (19 - 45) P1: 14 (warfarin); P2: 12 (warfarin + teriflunomide) Healthy INT10563 * Assess effect of 14-day repeated oral doses of teriflunomide on PK of midazolam, as a probe substrate for CYP3A activity. Teriflunomide 14mg tablets 70mg (5 tablets) QD 3d followed by 14mg maintenance dose QD 11d 26/23 26M