{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:29:35Z","timestamp":1790562575032,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007152","name":"Vivus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the pharmacokinetic (PK) and pharmacodynamic characteristics of VI\u20100521, a fixed\u2010dose combination of immediate\u2010release phentermine (PHEN) and extended\u2010release topiramate (TPM) in adolescents aged 12 to 17\u2009years with obesity, and to report weight loss and adverse events using this drug combination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This was a multicentre, randomized, double\u2010blind, parallel\u2010design, placebo\u2010controlled study in adolescents with obesity. A total of 42 adolescents were randomly assigned in a 1:1:1 ratio to placebo, or to a mid\u2010dose (PHEN\/TPM 7.5\u2009mg\/46\u2009mg), or a top\u2010dose (PHEN\/TPM 15\u2009mg\/92\u2009mg) of VI\u20100521. A total of 26 adolescents were included in the PK analysis (14 from the mid\u2010dose group and 12 from the top\u2010dose group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>On day 56, arithmetic means of terminal elimination half\u2010life, apparent clearance (CL\/F) and apparent central volume of distribution (Vc\/F) were consistent across dose levels for both PHEN and TPM. Arithmetic means of CL\/F and Vc\/F for PHEN and TPM administered as a combination in adolescents with obesity were within 10% to 30% of those previously assessed in adults with obesity enrolled in phase II and III studies. A higher proportion of adolescents in both the mid\u2010 and top\u2010dose groups (13.3% and 50.0%, respectively) compared with placebo (0.0%) reached \u22655% weight loss at day 56. The least squares (LS) mean change in systolic blood pressure from baseline to day 56 was \u22125.2\u2009mmHg for the placebo group, \u22122.5\u2009mmHg for the mid\u2010dose group, and\u2009\u2212\u20095.5\u2009mmHg for the top\u2010dose group. The LS mean change in diastolic blood pressure from baseline to day 56 was \u22122.4\u2009mmHg for the placebo group, +3.8\u2009mmHg for the mid\u2010dose group, and\u2009+\u20092.0\u2009mmHg for the top\u2010dose group. Participants in the top\u2010dose group had increases in heart rate from baseline of 4.1\u2009bpm, while participants in the mid\u2010dose group experienced a mean decrease in heart rate of 4.5\u2009bpm at day 56. Both PHEN\/TPM dose combinations were safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment of adolescents with obesity using a fixed\u2010dose combination of PHEN\/TPM for 8\u2009weeks resulted in exposure to PHEN and TPM that was comparable to that observed in adults, statistically significant weight loss, and a tolerable safety profile. These data indicate that both mid\u2010 and top\u2010dose levels are appropriate for longer\u2010term safety and efficacy studies in adolescents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13910","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:30:01Z","timestamp":1573086601000},"page":"480-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["A randomized, double\u2010blind, placebo\u2010controlled, pharmacokinetic and pharmacodynamic study of a fixed\u2010dose combination of phentermine\/topiramate in adolescents with obesity"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2832-3429","authenticated-orcid":false,"given":"Daniel S.","family":"Hsia","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center  Baton Rouge Louisiana United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie H.","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Certara USA, Inc  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Williams","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital\/University of Cincinnati  Cincinnati Ohio United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Farhat","sequence":"additional","affiliation":[{"name":"Certara USA, Inc  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. F.","family":"Marier","sequence":"additional","affiliation":[{"name":"Certara USA, Inc  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Shih","sequence":"additional","affiliation":[{"name":"Vivus, Inc  Campbell California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Peterson","sequence":"additional","affiliation":[{"name":"Vivus, Inc  Campbell California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Siegel","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital\/University of Cincinnati  Cincinnati Ohio United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.3060"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.5158"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22196"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.9778\/cmajo.20140047"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001872.pub2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsu023"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-015-1382-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12316"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12334"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281361"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2016.69"},{"key":"e_1_2_8_13_1","first-page":"267","article-title":"Phentermine and topiramate for the management of obesity: a review","volume":"7","author":"Cosentino G","year":"2013","journal-title":"Drug Des Devel Ther"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.5455\/2319-2003.ijbcp20140634"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60205-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.05.014"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2010.00846.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.25.4.135"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(85)80697-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80479-5"},{"key":"e_1_2_8_21_1","unstructured":"MarierJF MouksassiMS GosselinNH YeeS PetersonC DayW. 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