Biopharmaceutics Several biopharmacetic studies were provided in support of this submission. The following studies were evaluated (see 2): 2: Biopharmaceutic studies submitted number Study type Study SPD503-104 Food effect (single 4 Full Food increased mg) Cmax and AUC by (food effect & relative 75% and 38%, bioavailability) Relative respectively. bioavailability (1 x4 mg vs 4 x 1 mg) Study503-109 Dose proportional Full The investigators 1, 2, 4 mg tablet concluded that (dose proportional) formulation. tablets (relative manufactured at BE of SPD503 bioequivalence of 2 mg the two sites tablets and 4 mg at initial were manufactured at the development site bioequivalent initial development versus initial and that site and initial commercial exposure from commercial manufacturing site the three manufacturing site strengths was following single doses of 2 and 4mg, respectively. SPD503-120 To assess the Full The investigators bioequivalence of concluded that (relative 4mg SPD503 tablets tablets bioequivalence of 4 mg manufactured at the manufactured at at initial commercial 2 different sites the two were manufacturing site following a single bioequivalent. versus current dose of SPD503. commercial manufacturing site SPD503-203 Phase II PK profile of SPD503 after a (steady state 1 mg and 1mg single dose and 4 mg) multiple dosing of 1 and 4 mg/day, in paediatric patients. The results of the biostudies provided support the conclusions that: Food has a significant effect on the pharmacokinetics of guanfacine, with administration after a high-fat meal increasing peak plasma concentration (Cmax) by 75% and area under the plasma concentration versus time curve (AUC) by 38%, and 1 x 4 mg tablet is bioequivalent to 4 x 1 mg tablets, The tablets manufactured at the [information redacted] site are bioequivalent to the same strength tablets manufactured at the [information redacted] site, and
Biopharmaceutics Several biopharmacetic studies were provided in support of this submission. The following studies were evaluated (see 2): 2: Biopharmaceutic studies submitted number Study type Study SPD503-104 (food effect & relative bioavailability) Food effect (single 4 mg) Relative bioavailability (1 x4 mg vs 4 x 1 mg) Full Food increased Cmax and AUC by 75% and 38%, respectively. Study503-109 (dose proportional) (relative bioequivalence of 2 mg and 4 mg at initial development site versus initial commercial manufacturing site Dose proportional 1, 2, 4 mg tablet formulation. BE of SPD503 tablets manufactured at the initial development site and initial commercial manufacturing site following single doses of 2 and 4mg, respectively. Full The investigators concluded that tablets manufactured at the two sites were bioequivalent and that exposure from the three strengths was SPD503-120 (relative bioequivalence of 4 mg at initial commercial manufacturing site versus current commercial manufacturing site To assess the bioequivalence of 4mg SPD503 tablets manufactured at the 2 different sites following a single dose of SPD503. Full The investigators concluded that tablets manufactured at the two were bioequivalent. SPD503-203 (steady state 1 mg and 4 mg) Phase II PK profile of SPD503 after a 1mg single dose and multiple dosing of 1 and 4 mg/day, in paediatric patients. The results of the biostudies provided support the conclusions that: Food has a significant effect on the pharmacokinetics of guanfacine, with administration after a high-fat meal increasing peak plasma concentration (Cmax) by 75% and area under the plasma concentration versus time curve (AUC) by 38%, and 1 x 4 mg tablet is bioequivalent to 4 x 1 mg tablets, The tablets manufactured at the [information redacted] site are bioequivalent to the same strength tablets manufactured at the [information redacted] site, and