{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:18:48Z","timestamp":1787663928518,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Limb\u2010girdle muscle dystrophy Type R9 (LGMDR9), also known as LGMD Type 2I, is a rare genetic disease caused by partial loss of function of fukutin\u2010related protein (FKRP) enzyme which glycosylates alpha\u2010dystroglycan, thereby stabilizing myocytes during contraction. Hypoglycosylation leads to progressive muscle injury and impaired function including loss of ambulation. Ribitol is an endogenous pentose alcohol and precursor to CDP\u2010ribitol, the substrate of FKRP. This first\u2010in\u2010human study demonstrated that ribitol was well tolerated when administered as single or multiple oral doses over 6 days to healthy adults. PK demonstrated dose\u2010proportional increases in exposure from 0.5 to 15 g (therapeutic dose 9 and 12 g BID for patients weighing &gt;30 to \u226450 kg and &gt;50 kg, respectively); t\n                    <jats:sub>\u00bd<\/jats:sub>\n                    was 9\u201013\u00a0h. A high\u2010fat meal did not affect overall oral bioavailability; indicating ribitol may be taken without regard to food intake. A dedicated QT study using ribitol 21 g revealed no concentration\u2010dependent QTcF prolongation and clinically significant QTcF prolongation was excluded over the entire range of exposures in the study, up to 351.9\u00a0\u00b5g\/mL. Assay sensitivity was demonstrated with the expected effect of moxifloxacin. These results support further development of ribitol for the treatment of LGMDR9.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70082","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:18:30Z","timestamp":1785413910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Tolerability, Pharmacokinetics, Food Effect of Ribitol, and Its Effect on QTcF in Healthy Adults: First\u2010in\u2010Human, Randomized, Double\u2010Blind (Sponsor Unblinded), Placebo\u2010Controlled Studies"],"prefix":"10.1002","volume":"15","author":[{"given":"Daniel D.","family":"Gretler","sequence":"first","affiliation":[{"name":"Bridgebio Pharma, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athiwat","family":"Hutchaleelaha","sequence":"additional","affiliation":[{"name":"Bridgebio Pharma, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Sinha","sequence":"additional","affiliation":[{"name":"Bridgebio Pharma, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Rickert","sequence":"additional","affiliation":[{"name":"Bridgebio Pharma, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug","family":"Sproule","sequence":"additional","affiliation":[{"name":"Bridgebio Pharma, Inc.  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/324412"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-150105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11534"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.2.251"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63160-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51042"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05990-z"},{"key":"e_1_2_9_9_1","unstructured":"U.S. Food and Drug Administration.Assessing the effects of food on drugs in INDs and NDAs\u2014clinical pharmacology considerations: guidance for industry. U.S. Food and Drug Administration. May 2026. Accessed June 8 2026.https:\/\/www.fda.gov\/media\/121313\/download"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_9_11_1","unstructured":"U.S. Food and Drug Administration.E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs: guidance for industry. October 2005. Accessed June 8 2026.https:\/\/www.fda.gov\/media\/71372\/download"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1545"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1979.10481038"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9868.00125"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.9927"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.01.005"},{"issue":"5","key":"e_1_2_9_17_1","article-title":"Safety of D\u2010ribose as a novel food pursuant to Regulation (EU) 2015\/2283","volume":"16","author":"Turck D","year":"2018","journal-title":"EFSA J"},{"issue":"1","key":"e_1_2_9_18_1","first-page":"1","article-title":"Differential efficiency and pathway of ribitol, ribulose and ribose for enhancing matriglycan expression","volume":"14","author":"Lu Q","year":"2026","journal-title":"Med Res Arch"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70082","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70082","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:23:47Z","timestamp":1787660627000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cpdd.70082"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70082","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"assertion":[{"value":"2026-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70082"}}