{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:22:51Z","timestamp":1788481371995,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcopenia is an age\u2010related skeletal muscle disorder characterized by loss of muscle mass and strength leading to mobility disability. 20\u2010Hydroxyecdysone (20E) is a polyhydroxylated plant steroid that demonstrates pharmacological effects in many disease animal models including ageing\/sarcopenia. BIO101 is a 20E purified investigational drug (\u226597%) that previously demonstrated good toxicology profiles in rat and dog. BIO101 is evaluated in healthy young and older adults in a Phase 1 study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study is a Single Ascending Dose (SAD) followed by a 14\u2010day Multiple Ascending Dose (MAD). In SAD, BIO101 was administered orally to 16 young adults at doses from 100 to 1400\u00a0mg and to 8 older adults (age \u226565\u00a0years) at 1400\u00a0mg. In MAD, doses of 350\u00a0mg once daily (qd), 350\u00a0mg twice daily (bid) and 450\u00a0mg bid were administered to 10 older adults. The primary objective was to evaluate safety and pharmacokinetics (PK), including dosing of circulating metabolites. Pharmacodynamic effects were investigated with regard to myostatin, procollagen\u2010III\u2010amino\u2010terminal propeptide (PIIINP), myoglobin, creatine\u2010kinase Muscle Brain (CKMB), renin and aldosterone plasma\/serum levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BIO101 showed a good safety profile with only mild to moderate adverse events and a satisfactory pharmacokinetic profile. In SAD, at 100\u00a0mg to 1400\u00a0mg, mean Cmax and areas under the curve increased less than dose\u2010proportionally. Mean half\u2010life was short (2.4\u20134.9\u00a0h), and mean renal clearance was comparable in all doses (4.05\u20135.05\u00a0L\/h). Mean plasma exposure was slightly lower in older adults (22% lower for Cmax and 13%\u201315% lower for AUCs) compared with young subjects. In MAD, 350 and 450\u00a0mg bid led to a slight accumulation over 14\u00a0days (mean ratio of accumulation [Rac] of 1.31 in both cohorts). Reduction of biomarkers (myoglobin, CK\u2010MB) mean serum levels (vs. baseline) was observed at 450\u00a0mg bid. Two major metabolites of 20E (14\u2010deoxy\u201020\u2010hydroxyecdysone and 14\u2010deoxypoststerone) were identified and quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BIO101 shows a good safety and pharmacokinetic profile that led to the selection of doses for the subsequent interventional clinical trials of Phase 2 in age\u2010related sarcopenia (SARA\u2010INT) and Phase 3 in Covid\u201019 (COVA).<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13195","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T06:41:52Z","timestamp":1681454512000},"page":"1259-1273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Phase 1 study for safety and pharmacokinetics of BIO101 (20\u2010hydroxyecdysone) in healthy young and older adults"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-028X","authenticated-orcid":false,"given":"Waly","family":"Dioh","sequence":"first","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cendrine","family":"Tourette","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Del Signore","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"},{"name":"Bluecompanion Ltd  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louiza","family":"Daudigny","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Dupont","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Balducci","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre J.","family":"Dilda","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Lafont","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"},{"name":"FSI, Paris\u2010Seine Biology Institute (BIOSIPE), CNRS Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislas","family":"Veillet","sequence":"additional","affiliation":[{"name":"Biophytis Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"33","article-title":"Muscle disuse as a pivotal problem in sarcopenia\u2010related muscle loss and dysfunction","volume":"5","author":"Bell KE","year":"2016","journal-title":"J Frailty Aging"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40200-017-0302-x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-0022-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-018-0566-y"},{"key":"e_1_2_8_6_1","first-page":"120","article-title":"Development of pharmacotherapies for the treatment of sarcopenia","volume":"8","author":"Rooks D","year":"2019","journal-title":"J Frailty Aging"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31138-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy169"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00234"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-011-0034-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-013-0335-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.17987\/jcsm-cr.v2i1.37"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.14927"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly277"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06900"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf073059z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","unstructured":"DildaP FoucaultA SerovaM OnS RaynalS VeilletS et al.BIO101 a drug candidate targeting Mas Receptor for the treatment of age\u2010related muscle degeneration. 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