Table14. Submitted pharmacodynamic studies. Study Objective(s) Treatment Subjects * Study design M/F Assess effect of repeated of Teriflunomide tablets: 70mg QD for first 4 days, then14mg QD for 192/179 teriflunomide on QTcF interval, compared 8 days, (87M/95F) to placebo and using moxifloxacin * Placebo: matched to teriflunomide tablets QD for 14days healthy subjects (400mg, single dose) as a positive control single Moxifloxacin capsules: 400mg on D12 Teriflunomide: 64 Randomized, double-blind, centre All treatments preceded by a placebo run-in day repeated dose, Placebo: 56 controlled study, stratified by gender, Placebo: matched to moxifloxacin capsules QD for 11days Moxifloxacin: 62 conducted in 3 parallel groups (moxifloxacin group ) or 12days (teriflunomide and placebo 41.6 ± 16.1 Mar groups) 2010 - (18 65) yr – Feb 2011 Assess effect of repeated daily oral doses Teriflunomide 14mg tablets 14/12 40 of teriflunomide on PD and PK profile of Loading dose of 70mg QD for first3d of P2, followed by 14mg QD 14M warfarin after a single oral dose of 25mg * for 8 consecutive days 31.0 ± 9.0 (19 - warfarin; assess safety of teriflunomide co 1 Warfarin 5mg tablets 45) administered with warfarin compared to centre warfarin alone Single dose of 25mg (5 tablets) on P1, Dl and on P2, D5 P1: 14 (warfarin); UK Open, nonrandomized, single sequence, 2- Cholestyramine for 11d (D12 to D22) P2: 12 (warfarin+ treatment, 2-period study Feb – Teriflunomide: 11d teriflunomide) Jul Warfarin: 2d Healthy 2007
Table14. Submitted pharmacodynamic studies. Study * Objective(s) Study design Treatment Subjects M/F * single centre Mar 2010 - Feb 2011 Assess effect of repeated of teriflunomide on QTcF interval, compared to placebo and using moxifloxacin (400mg, single dose) as a positive control Randomized, double-blind, repeated dose, study, stratified by gender, conducted in 3 parallel groups Teriflunomide tablets: 70mg QD for first 4 days, then14mg QD for 8 days, Placebo: matched to teriflunomide tablets QD for 14days Moxifloxacin capsules: 400mg on D12 All treatments preceded by a placebo run-in day Placebo: matched to moxifloxacin capsules QD for 11days (moxifloxacin group ) or 12days (teriflunomide and placebo groups) 192/179 (87M/95F) healthy subjects Teriflunomide: 64 Placebo: 56 Moxifloxacin: 62 41.6 ± 16.1 (18 – 65) yr * 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 study 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 controlled 40
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