AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial
Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in anim...
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| Veröffentlicht in: | PloS one 2018-01, Vol.13 (1), p.e0190849-e0190849 |
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| creator | Allas, Soraya Caixàs, Assumpta Poitou, Christine Coupaye, Muriel Thuilleaux, Denise Lorenzini, Françoise Diene, Gwenaëlle Crinò, Antonino Illouz, Frédéric Grugni, Graziano Potvin, Diane Bocchini, Sarah Delale, Thomas Abribat, Thierry Tauber, Maithé |
| description | Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.
Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.
AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.
AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials. |
| doi_str_mv | 10.1371/journal.pone.0190849 |
| format | Article |
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Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.
AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.
AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0190849</identifier><identifier>PMID: 29320575</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Analysis ; Appetite ; Biology and Life Sciences ; Body composition ; Body fat ; Body weight ; Bone diseases ; Care and treatment ; Children & youth ; Clinical trials ; Cognitive ability ; Diabetes ; Endocrinology ; Food ; Genetic aspects ; Ghrelin ; Glucose ; Gynecology ; Hyperphagia ; Laboratory tests ; Life Sciences ; Medical research ; Medicine and Health Sciences ; Mortality ; Nutrition ; Obesity ; Oxidative stress ; Patients ; Physical Sciences ; Prader-Willi syndrome ; Product development ; Quality of life ; Randomization ; Safety ; Weight reduction</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0190849-e0190849</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Allas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2018 Allas et al 2018 Allas et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c726t-52a214ce795d926ac8ef4e244c1c71f8370d8ca5c0a64629d565a711a335a1cc3</citedby><cites>FETCH-LOGICAL-c726t-52a214ce795d926ac8ef4e244c1c71f8370d8ca5c0a64629d565a711a335a1cc3</cites><orcidid>0000-0002-3547-7883 ; 0009-0003-8970-0088</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761957/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761957/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23864,27922,27923,53789,53791,79370,79371</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29320575$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04013074$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Buchowski, Maciej</contributor><creatorcontrib>Allas, Soraya</creatorcontrib><creatorcontrib>Caixàs, Assumpta</creatorcontrib><creatorcontrib>Poitou, Christine</creatorcontrib><creatorcontrib>Coupaye, Muriel</creatorcontrib><creatorcontrib>Thuilleaux, Denise</creatorcontrib><creatorcontrib>Lorenzini, Françoise</creatorcontrib><creatorcontrib>Diene, Gwenaëlle</creatorcontrib><creatorcontrib>Crinò, Antonino</creatorcontrib><creatorcontrib>Illouz, Frédéric</creatorcontrib><creatorcontrib>Grugni, Graziano</creatorcontrib><creatorcontrib>Potvin, Diane</creatorcontrib><creatorcontrib>Bocchini, Sarah</creatorcontrib><creatorcontrib>Delale, Thomas</creatorcontrib><creatorcontrib>Abribat, Thierry</creatorcontrib><creatorcontrib>Tauber, Maithé</creatorcontrib><title>AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.
Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.
AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.
AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.</description><subject>Age</subject><subject>Analysis</subject><subject>Appetite</subject><subject>Biology and Life Sciences</subject><subject>Body composition</subject><subject>Body fat</subject><subject>Body weight</subject><subject>Bone diseases</subject><subject>Care and treatment</subject><subject>Children & youth</subject><subject>Clinical trials</subject><subject>Cognitive ability</subject><subject>Diabetes</subject><subject>Endocrinology</subject><subject>Food</subject><subject>Genetic aspects</subject><subject>Ghrelin</subject><subject>Glucose</subject><subject>Gynecology</subject><subject>Hyperphagia</subject><subject>Laboratory tests</subject><subject>Life Sciences</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mortality</subject><subject>Nutrition</subject><subject>Obesity</subject><subject>Oxidative 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titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allas, Soraya</au><au>Caixàs, Assumpta</au><au>Poitou, Christine</au><au>Coupaye, Muriel</au><au>Thuilleaux, Denise</au><au>Lorenzini, Françoise</au><au>Diene, Gwenaëlle</au><au>Crinò, Antonino</au><au>Illouz, Frédéric</au><au>Grugni, Graziano</au><au>Potvin, Diane</au><au>Bocchini, Sarah</au><au>Delale, Thomas</au><au>Abribat, Thierry</au><au>Tauber, Maithé</au><au>Buchowski, Maciej</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-01-10</date><risdate>2018</risdate><volume>13</volume><issue>1</issue><spage>e0190849</spage><epage>e0190849</epage><pages>e0190849-e0190849</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.
Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.
AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.
AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29320575</pmid><doi>10.1371/journal.pone.0190849</doi><tpages>e0190849</tpages><orcidid>https://orcid.org/0000-0002-3547-7883</orcidid><orcidid>https://orcid.org/0009-0003-8970-0088</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-01, Vol.13 (1), p.e0190849-e0190849 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1986388415 |
| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Analysis Appetite Biology and Life Sciences Body composition Body fat Body weight Bone diseases Care and treatment Children & youth Clinical trials Cognitive ability Diabetes Endocrinology Food Genetic aspects Ghrelin Glucose Gynecology Hyperphagia Laboratory tests Life Sciences Medical research Medicine and Health Sciences Mortality Nutrition Obesity Oxidative stress Patients Physical Sciences Prader-Willi syndrome Product development Quality of life Randomization Safety Weight reduction |
| title | AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T23%3A44%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AZP-531,%20an%20unacylated%20ghrelin%20analog,%20improves%20food-related%20behavior%20in%20patients%20with%20Prader-Willi%20syndrome:%20A%20randomized%20placebo-controlled%20trial&rft.jtitle=PloS%20one&rft.au=Allas,%20Soraya&rft.date=2018-01-10&rft.volume=13&rft.issue=1&rft.spage=e0190849&rft.epage=e0190849&rft.pages=e0190849-e0190849&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0190849&rft_dat=%3Cgale_plos_%3EA522513317%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1986388415&rft_id=info:pmid/29320575&rft_galeid=A522513317&rft_doaj_id=oai_doaj_org_article_ff6cefe6e0af477b8ee96a2778760a9d&rfr_iscdi=true |