Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study
This study evaluated the effect of a small‐tablet formulation of opicapone for use in clinical trials in Japan on the pharmacokinetics of levodopa (l‐dopa) and 3‐O‐methyldopa (3‐OMD). In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years;...
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| Veröffentlicht in: | Clinical pharmacology in drug development 2021-02, Vol.10 (2), p.180-189 |
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| creator | Nomoto, Masahiro Takeda, Atsushi Iwai, Katsuaki Nishimura, Akihisa Hattori, Nobutaka |
| description | This study evaluated the effect of a small‐tablet formulation of opicapone for use in clinical trials in Japan on the pharmacokinetics of levodopa (l‐dopa) and 3‐O‐methyldopa (3‐OMD). In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years; body mass index, 18.5 to |
| doi_str_mv | 10.1002/cpdd.799 |
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In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years; body mass index, 18.5 to <30.0 kg/m2), 10 mg of l‐dopa/carbidopa 100 was administered 3 times daily on day 0 (period 1) and day 12 (period 3), and opicapone tablets (5, 10, 25, or 50 mg; n = 20 each group) were administered once daily for 11 days (period 2). During periods 1 and 3, plasma concentrations of l‐dopa and 3‐OMD were measured and pharmacokinetic parameters (maximum observed plasma concentration, time at which maximum concentration was observed, area under the plasma concentration–time curve from time 0 to 5 hours [AUC5h] and from time 0 to 24 hours [AUC24h] following each dose, terminal half‐life) of plasma l‐dopa and 3‐OMD were determined along with the geometric mean ratio (period 3/period 1) of AUC24h for l‐dopa and 3‐OMD. Maximum concentration of l‐dopa for the first, second, or third doses of l‐dopa/carbidopa did not significantly increase with increasing opicapone dose. The AUC of l‐dopa increased with increasing opicapone dose but tended toward a peak plateau with opicapone doses of 25 mg and higher. Geometric mean ratios (90% confidence intervals) of AUC24h were 5 mg, 1.16 (1.10‐1.21); 10 mg, 1.26 (1.23‐1.30); 25 mg, 1.51 (1.44‐1.57); 50 mg, 1.60 (1.54‐1.66). Opicapone tablets were well tolerated. In Japanese healthy subjects, increases in plasma exposure to l‐dopa appear to level off with opicapone doses of 25 mg and higher, which may be relevant for optimal dosing among Japanese patients with Parkinson disease.</description><identifier>ISSN: 2160-763X</identifier><identifier>EISSN: 2160-7648</identifier><identifier>DOI: 10.1002/cpdd.799</identifier><identifier>PMID: 32416054</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject><![CDATA[3‐OMD ; Adult ; Antiparkinson Agents - administration & dosage ; Antiparkinson Agents - pharmacokinetics ; Area Under Curve ; Asians ; Carbidopa - administration & dosage ; Carbidopa - pharmacokinetics ; Catechol O-Methyltransferase Inhibitors - administration & dosage ; Catechol O-Methyltransferase Inhibitors - pharmacokinetics ; COMT inhibitor ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Drug Combinations ; Half-Life ; Humans ; Japanese ; levodopa ; Levodopa - administration & dosage ; Levodopa - pharmacokinetics ; Male ; Middle Aged ; opicapone ; Original Manuscript ; Oxadiazoles - administration & dosage ; Oxadiazoles - pharmacology ; Parkinson disease ; Parkinson's disease ; pharmacokinetic ; Pharmacokinetics ; phase 1 ; Plasma ; Tablets ; Tyrosine - analogs & derivatives ; Tyrosine - pharmacokinetics ; Young Adult]]></subject><ispartof>Clinical pharmacology in drug development, 2021-02, Vol.10 (2), p.180-189</ispartof><rights>2020 The Authors. published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology</rights><rights>2020 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4389-a12a190be041d99eb39b350eef1bf22ff577f968b8111fdbcbb605b2a4b6551e3</citedby><cites>FETCH-LOGICAL-c4389-a12a190be041d99eb39b350eef1bf22ff577f968b8111fdbcbb605b2a4b6551e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpdd.799$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpdd.799$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32416054$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nomoto, Masahiro</creatorcontrib><creatorcontrib>Takeda, Atsushi</creatorcontrib><creatorcontrib>Iwai, Katsuaki</creatorcontrib><creatorcontrib>Nishimura, Akihisa</creatorcontrib><creatorcontrib>Hattori, Nobutaka</creatorcontrib><title>Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study</title><title>Clinical pharmacology in drug development</title><addtitle>Clin Pharmacol Drug Dev</addtitle><description>This study evaluated the effect of a small‐tablet formulation of opicapone for use in clinical trials in Japan on the pharmacokinetics of levodopa (l‐dopa) and 3‐O‐methyldopa (3‐OMD). In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years; body mass index, 18.5 to <30.0 kg/m2), 10 mg of l‐dopa/carbidopa 100 was administered 3 times daily on day 0 (period 1) and day 12 (period 3), and opicapone tablets (5, 10, 25, or 50 mg; n = 20 each group) were administered once daily for 11 days (period 2). During periods 1 and 3, plasma concentrations of l‐dopa and 3‐OMD were measured and pharmacokinetic parameters (maximum observed plasma concentration, time at which maximum concentration was observed, area under the plasma concentration–time curve from time 0 to 5 hours [AUC5h] and from time 0 to 24 hours [AUC24h] following each dose, terminal half‐life) of plasma l‐dopa and 3‐OMD were determined along with the geometric mean ratio (period 3/period 1) of AUC24h for l‐dopa and 3‐OMD. Maximum concentration of l‐dopa for the first, second, or third doses of l‐dopa/carbidopa did not significantly increase with increasing opicapone dose. The AUC of l‐dopa increased with increasing opicapone dose but tended toward a peak plateau with opicapone doses of 25 mg and higher. Geometric mean ratios (90% confidence intervals) of AUC24h were 5 mg, 1.16 (1.10‐1.21); 10 mg, 1.26 (1.23‐1.30); 25 mg, 1.51 (1.44‐1.57); 50 mg, 1.60 (1.54‐1.66). Opicapone tablets were well tolerated. In Japanese healthy subjects, increases in plasma exposure to l‐dopa appear to level off with opicapone doses of 25 mg and higher, which may be relevant for optimal dosing among Japanese patients with Parkinson disease.</description><subject>3‐OMD</subject><subject>Adult</subject><subject>Antiparkinson Agents - administration & dosage</subject><subject>Antiparkinson Agents - pharmacokinetics</subject><subject>Area Under Curve</subject><subject>Asians</subject><subject>Carbidopa - administration & dosage</subject><subject>Carbidopa - pharmacokinetics</subject><subject>Catechol O-Methyltransferase Inhibitors - administration & dosage</subject><subject>Catechol O-Methyltransferase Inhibitors - pharmacokinetics</subject><subject>COMT inhibitor</subject><subject>Cross-Over Studies</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Combinations</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Japanese</subject><subject>levodopa</subject><subject>Levodopa - administration & dosage</subject><subject>Levodopa - pharmacokinetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>opicapone</subject><subject>Original Manuscript</subject><subject>Oxadiazoles - administration & dosage</subject><subject>Oxadiazoles - pharmacology</subject><subject>Parkinson disease</subject><subject>Parkinson's disease</subject><subject>pharmacokinetic</subject><subject>Pharmacokinetics</subject><subject>phase 1</subject><subject>Plasma</subject><subject>Tablets</subject><subject>Tyrosine - analogs & derivatives</subject><subject>Tyrosine - pharmacokinetics</subject><subject>Young Adult</subject><issn>2160-763X</issn><issn>2160-7648</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kd1KHDEUx0OpVFGhT1ACvenNaJLJfKQXhbLrR8uWFVTwLiSZk-5sZ5NxMqMs3vgIPqNPYtbVpV4YCDnJ-fE_5-SP0GdKDigh7NC0VXVQCPEB7TCak6TIeflxE6dX22g_hDmJKyeUUv4JbaeMx2zGd9DdkbVgeuwtnra1Ua13gC-UbqAP2Ds8gRtf-VZh5SqcPt4_TOP-A_1s2Tw_n81Ut1DG_6sd9LUJuHb4FFQTAfxbtcpBAHw-6HksEr6v8Hin-LwfquUe2rKqCbD_cu6iy-Oji9FpMpme_Br9nCSGp6VIFGWKCqKBcFoJAToVOs0IgKXaMmZtVhRW5KUu43S20kbrOJtmius8yyiku-jHWrcd9AIqA67vVCPbrl6obim9quXbjKtn8q-_kUUp4jflUeDri0DnrwcIvZz7oXOxZ8l4yZnglJJIfVtTpvMhdGA3FSiRK6fkyikZnYrol_872oCvvkQgWQO3dQPLd4Xk6Gw8Xgk-AcOQoJk</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Nomoto, Masahiro</creator><creator>Takeda, Atsushi</creator><creator>Iwai, Katsuaki</creator><creator>Nishimura, Akihisa</creator><creator>Hattori, Nobutaka</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>202102</creationdate><title>Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study</title><author>Nomoto, Masahiro ; Takeda, Atsushi ; Iwai, Katsuaki ; Nishimura, Akihisa ; Hattori, Nobutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4389-a12a190be041d99eb39b350eef1bf22ff577f968b8111fdbcbb605b2a4b6551e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>3‐OMD</topic><topic>Adult</topic><topic>Antiparkinson Agents - administration & dosage</topic><topic>Antiparkinson Agents - pharmacokinetics</topic><topic>Area Under Curve</topic><topic>Asians</topic><topic>Carbidopa - administration & dosage</topic><topic>Carbidopa - pharmacokinetics</topic><topic>Catechol O-Methyltransferase Inhibitors - administration & dosage</topic><topic>Catechol O-Methyltransferase Inhibitors - pharmacokinetics</topic><topic>COMT inhibitor</topic><topic>Cross-Over Studies</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Combinations</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Japanese</topic><topic>levodopa</topic><topic>Levodopa - administration & dosage</topic><topic>Levodopa - pharmacokinetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>opicapone</topic><topic>Original Manuscript</topic><topic>Oxadiazoles - administration & dosage</topic><topic>Oxadiazoles - pharmacology</topic><topic>Parkinson disease</topic><topic>Parkinson's disease</topic><topic>pharmacokinetic</topic><topic>Pharmacokinetics</topic><topic>phase 1</topic><topic>Plasma</topic><topic>Tablets</topic><topic>Tyrosine - analogs & derivatives</topic><topic>Tyrosine - pharmacokinetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nomoto, Masahiro</creatorcontrib><creatorcontrib>Takeda, Atsushi</creatorcontrib><creatorcontrib>Iwai, Katsuaki</creatorcontrib><creatorcontrib>Nishimura, Akihisa</creatorcontrib><creatorcontrib>Hattori, Nobutaka</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology in drug development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nomoto, Masahiro</au><au>Takeda, Atsushi</au><au>Iwai, Katsuaki</au><au>Nishimura, Akihisa</au><au>Hattori, Nobutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study</atitle><jtitle>Clinical pharmacology in drug development</jtitle><addtitle>Clin Pharmacol Drug Dev</addtitle><date>2021-02</date><risdate>2021</risdate><volume>10</volume><issue>2</issue><spage>180</spage><epage>189</epage><pages>180-189</pages><issn>2160-763X</issn><eissn>2160-7648</eissn><abstract>This study evaluated the effect of a small‐tablet formulation of opicapone for use in clinical trials in Japan on the pharmacokinetics of levodopa (l‐dopa) and 3‐O‐methyldopa (3‐OMD). In an open‐label, 3‐period, single‐sequence crossover phase 1 study in 80 healthy Japanese males (aged 20‐45 years; body mass index, 18.5 to <30.0 kg/m2), 10 mg of l‐dopa/carbidopa 100 was administered 3 times daily on day 0 (period 1) and day 12 (period 3), and opicapone tablets (5, 10, 25, or 50 mg; n = 20 each group) were administered once daily for 11 days (period 2). During periods 1 and 3, plasma concentrations of l‐dopa and 3‐OMD were measured and pharmacokinetic parameters (maximum observed plasma concentration, time at which maximum concentration was observed, area under the plasma concentration–time curve from time 0 to 5 hours [AUC5h] and from time 0 to 24 hours [AUC24h] following each dose, terminal half‐life) of plasma l‐dopa and 3‐OMD were determined along with the geometric mean ratio (period 3/period 1) of AUC24h for l‐dopa and 3‐OMD. Maximum concentration of l‐dopa for the first, second, or third doses of l‐dopa/carbidopa did not significantly increase with increasing opicapone dose. The AUC of l‐dopa increased with increasing opicapone dose but tended toward a peak plateau with opicapone doses of 25 mg and higher. Geometric mean ratios (90% confidence intervals) of AUC24h were 5 mg, 1.16 (1.10‐1.21); 10 mg, 1.26 (1.23‐1.30); 25 mg, 1.51 (1.44‐1.57); 50 mg, 1.60 (1.54‐1.66). Opicapone tablets were well tolerated. In Japanese healthy subjects, increases in plasma exposure to l‐dopa appear to level off with opicapone doses of 25 mg and higher, which may be relevant for optimal dosing among Japanese patients with Parkinson disease.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32416054</pmid><doi>10.1002/cpdd.799</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3‐OMD Adult Antiparkinson Agents - administration & dosage Antiparkinson Agents - pharmacokinetics Area Under Curve Asians Carbidopa - administration & dosage Carbidopa - pharmacokinetics Catechol O-Methyltransferase Inhibitors - administration & dosage Catechol O-Methyltransferase Inhibitors - pharmacokinetics COMT inhibitor Cross-Over Studies Dose-Response Relationship, Drug Drug Combinations Half-Life Humans Japanese levodopa Levodopa - administration & dosage Levodopa - pharmacokinetics Male Middle Aged opicapone Original Manuscript Oxadiazoles - administration & dosage Oxadiazoles - pharmacology Parkinson disease Parkinson's disease pharmacokinetic Pharmacokinetics phase 1 Plasma Tablets Tyrosine - analogs & derivatives Tyrosine - pharmacokinetics Young Adult |
| title | Effect of Opicapone Tablets on Levodopa and 3‐O‐Methyldopa Pharmacokinetics in Healthy Japanese Subjects: Phase 1 Study |
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