Nov 2010 8 healthy – Mar 2011 Extrinsic Factor PK Study Reports INT6039 Effect of repeated doses of rifampin on PK profile of Teriflunomide 14mg tablets 21/19 (D1003) a single 70-mg dose of teriflunomide Single dose of 70mg (5 tablets) on D8 of each 21M Healthy * Single-dose, open-label, randomized, 2-way period 31.0± 12.2 crossover study with 2 treatment periods 1 centre Rifampin 300mg capsules (teriflunomide alone and coadministration) and a USA Apr Aug 600mg QD for 22 d (Dl through D22) Group A: 11 washout period of at least 21 d between treatments – 2005 Cholestyramine for7d Group B: 10 INTl1720 Assess effect of repeated doses of teriflunomide on Teriflunomide 14mg tablets 36/34 PK of caffeine, omeprazole, and metoprolol used as * 70mg QD for 4 d (Dl through D4) in P2, then 14mg 36/0 probe substrates for their respective CYP1A2, QD for 9 d (D5 through D13) in P2 In fed 2 centres 28.1 ± 7.1 CYP2C19, and CYP2D6 activities. conditions (except when co administered with (18—46) France Open study using a single sequence 2 period cocktail (D12, P2) 32/3/1 crossover design Jan Apr 2011 Cocktail Caffeine: 25-mg vials; omeprazole: 20mg – Cocktail alone: Healthy subjects, excluding poor metabolizers of capsules; metoprolol: 100-mg coated tablets 36 CYP2C1 9 and 2D6 and subjects with Gilbert’s given as a single dose on Dl, P1, and D12, P2 orally syndrome Teriflunomide in fasted condition alone: 35 Cholestyramine for lld (Dl4 through D24) Teriflunomide: 13d
Nov 2010 – Mar 2011 8 healthy Extrinsic Factor PK Study Reports INT6039 (D1003) * 1 centre USA Apr – Aug 2005 Effect of repeated doses of rifampin on PK profile of a single 70-mg dose of teriflunomide Single-dose, open-label, randomized, 2-way crossover study with 2 treatment periods (teriflunomide alone and coadministration) and a washout period of at least 21 d between treatments Teriflunomide 14mg tablets Single dose of 70mg (5 tablets) on D8 of each period Rifampin 300mg capsules 600mg QD for 22 d (Dl through D22) Cholestyramine for7d 21/19 21M Healthy 31.0± 12.2 Group A: 11 Group B: 10 INTl1720 * 2 centres France Jan – Apr 2011 Assess effect of repeated doses of teriflunomide on PK of caffeine, omeprazole, and metoprolol used as probe substrates for their respective CYP1A2, CYP2C19, and CYP2D6 activities. Open study using a single sequence 2 period crossover design Healthy subjects, excluding poor metabolizers of CYP2C1 9 and 2D6 and subjects with Gilbert’s syndrome Teriflunomide 14mg tablets 70mg QD for 4 d (Dl through D4) in P2, then 14mg QD for 9 d (D5 through D13) in P2 In fed conditions (except when co administered with cocktail (D12, P2) Cocktail Caffeine: 25-mg vials; omeprazole: 20mg capsules; metoprolol: 100-mg coated tablets given as a single dose on Dl, P1, and D12, P2 orally in fasted condition Cholestyramine for lld (Dl4 through D24) Teriflunomide: 13d 36/34 36/0 28.1 ± 7.1 (18—46) 32/3/1 Cocktail alone: 36 Teriflunomide alone: 35
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