PubMed:36252412 JSONTXT

{"project":"Zierdiyeerkenaili_800_3","denotations":[{"id":"T1","span":{"begin":86,"end":91},"obj":"CI"},{"id":"T2","span":{"begin":346,"end":351},"obj":"CI"},{"id":"T3","span":{"begin":231,"end":234},"obj":"CI"},{"id":"T4","span":{"begin":419,"end":422},"obj":"CI"},{"id":"T5","span":{"begin":427,"end":430},"obj":"CI"},{"id":"T6","span":{"begin":450,"end":453},"obj":"CI"},{"id":"T7","span":{"begin":546,"end":549},"obj":"CI"},{"id":"T8","span":{"begin":571,"end":574},"obj":"CI"},{"id":"T9","span":{"begin":990,"end":993},"obj":"CI"},{"id":"T10","span":{"begin":1062,"end":1065},"obj":"CI"},{"id":"T11","span":{"begin":1214,"end":1217},"obj":"CI"},{"id":"T12","span":{"begin":1256,"end":1259},"obj":"CI"},{"id":"T13","span":{"begin":1368,"end":1371},"obj":"CI"},{"id":"T14","span":{"begin":1389,"end":1392},"obj":"CI"},{"id":"T15","span":{"begin":1480,"end":1483},"obj":"CI"},{"id":"T16","span":{"begin":1502,"end":1505},"obj":"CI"},{"id":"T17","span":{"begin":1608,"end":1611},"obj":"CI"},{"id":"T18","span":{"begin":1676,"end":1679},"obj":"CI"},{"id":"T19","span":{"begin":1711,"end":1714},"obj":"CI"},{"id":"T20","span":{"begin":1732,"end":1735},"obj":"CI"},{"id":"T21","span":{"begin":215,"end":229},"obj":"CI"},{"id":"T22","span":{"begin":108,"end":122},"obj":"CI"}],"text":"Randomized, crossover, open-label study of the relative bioavailability and safety of FT218, a once-nightly sodium oxybate formulation: Phase 1 study in healthy volunteers.\nOBJECTIVES: Treatment for narcolepsy with sodium oxybate (SXB) has required twice-nightly dosing, at bedtime and 2.5-4 h later. This study evaluated the pharmacokinetics of FT218, an investigational, extended-release, once-nightly formulation of SXB (ON-SXB), vs twice-nightly SXB.\nMETHODS: In this phase 1, open-label study, healthy volunteers were randomized (1:1) to ON-SXB 6 g or twice-nightly SXB (two 3-g doses administered 4 h apart); minimum 3-day washout before crossover. Doses were administered 2 h post-evening meal. Blood samples for pharmacokinetic assessments were collected predose and up to 14 h after the first dose during each treatment period.\nRESULTS: Twenty-eight participants were enrolled (mean age, 39.6 years; 54% women; 93% white). Mean ± SEM area under the concentration-time curve for ON-SXB was 282.7 ± 30.2  μg·h/mL vs 273.3 ± 27.8 μg·h/mL for twice-nightly SXB. Geometric mean ratio (GMR; 90% CI) was 102.9 (98.0-108.0). Maximum γ-hydroxybutyrate (GHB) plasma concentration (Cmax) was 65.8 ± 4.0 μg/mL for ON-SXB vs 77.1 ± 4.9 μg/mL for twice-nightly SXB (GMR [90% CI], 88.3 [80.5-97.0]). The GMR (90% CI) for GHB plasma concentrations 8 h post dose (C8h) for ON-SXB vs twice-nightly SXB was 61.7 (45.8-83.0). The most frequently reported adverse events were the same for ON-SXB and twice-nightly SXB (nausea, dizziness, somnolence, vomiting).\nCONCLUSIONS: GHB exposure and Cmax with one 6-g dose of ON-SXB were bioequivalent to those with two 3-g doses of twice-nightly SXB, whereas C8h was lower with ON-SXB. If approved, ON-SXB will provide a single bedtime oxybate option, with clinically relevant pharmacologic exposure during the entire sleep period."}

{"project":"yaoziqian_800_3","denotations":[{"id":"T1","span":{"begin":86,"end":91},"obj":"CI"},{"id":"T10","span":{"begin":990,"end":993},"obj":"CI"},{"id":"T11","span":{"begin":1062,"end":1065},"obj":"CI"},{"id":"T12","span":{"begin":1256,"end":1259},"obj":"CI"},{"id":"T13","span":{"begin":1368,"end":1371},"obj":"CI"},{"id":"T14","span":{"begin":1389,"end":1392},"obj":"CI"},{"id":"T15","span":{"begin":1480,"end":1483},"obj":"CI"},{"id":"T16","span":{"begin":1502,"end":1505},"obj":"CI"},{"id":"T17","span":{"begin":1608,"end":1611},"obj":"CI"},{"id":"T18","span":{"begin":1676,"end":1679},"obj":"CI"},{"id":"T19","span":{"begin":1711,"end":1714},"obj":"CI"},{"id":"T2","span":{"begin":215,"end":229},"obj":"CI"},{"id":"T20","span":{"begin":1732,"end":1735},"obj":"CI"},{"id":"T3","span":{"begin":108,"end":122},"obj":"CI"},{"id":"T4","span":{"begin":231,"end":234},"obj":"CI"},{"id":"T5","span":{"begin":346,"end":351},"obj":"CI"},{"id":"T6","span":{"begin":419,"end":422},"obj":"CI"},{"id":"T7","span":{"begin":450,"end":453},"obj":"CI"},{"id":"T8","span":{"begin":546,"end":549},"obj":"CI"},{"id":"T9","span":{"begin":571,"end":574},"obj":"CI"},{"id":"T21","span":{"begin":427,"end":430},"obj":"CI"},{"id":"T22","span":{"begin":1214,"end":1217},"obj":"CI"}],"text":"Randomized, crossover, open-label study of the relative bioavailability and safety of FT218, a once-nightly sodium oxybate formulation: Phase 1 study in healthy volunteers.\nOBJECTIVES: Treatment for narcolepsy with sodium oxybate (SXB) has required twice-nightly dosing, at bedtime and 2.5-4 h later. This study evaluated the pharmacokinetics of FT218, an investigational, extended-release, once-nightly formulation of SXB (ON-SXB), vs twice-nightly SXB.\nMETHODS: In this phase 1, open-label study, healthy volunteers were randomized (1:1) to ON-SXB 6 g or twice-nightly SXB (two 3-g doses administered 4 h apart); minimum 3-day washout before crossover. Doses were administered 2 h post-evening meal. Blood samples for pharmacokinetic assessments were collected predose and up to 14 h after the first dose during each treatment period.\nRESULTS: Twenty-eight participants were enrolled (mean age, 39.6 years; 54% women; 93% white). Mean ± SEM area under the concentration-time curve for ON-SXB was 282.7 ± 30.2  μg·h/mL vs 273.3 ± 27.8 μg·h/mL for twice-nightly SXB. Geometric mean ratio (GMR; 90% CI) was 102.9 (98.0-108.0). Maximum γ-hydroxybutyrate (GHB) plasma concentration (Cmax) was 65.8 ± 4.0 μg/mL for ON-SXB vs 77.1 ± 4.9 μg/mL for twice-nightly SXB (GMR [90% CI], 88.3 [80.5-97.0]). The GMR (90% CI) for GHB plasma concentrations 8 h post dose (C8h) for ON-SXB vs twice-nightly SXB was 61.7 (45.8-83.0). The most frequently reported adverse events were the same for ON-SXB and twice-nightly SXB (nausea, dizziness, somnolence, vomiting).\nCONCLUSIONS: GHB exposure and Cmax with one 6-g dose of ON-SXB were bioequivalent to those with two 3-g doses of twice-nightly SXB, whereas C8h was lower with ON-SXB. If approved, ON-SXB will provide a single bedtime oxybate option, with clinically relevant pharmacologic exposure during the entire sleep period."}