{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:35:01Z","timestamp":1769222101636,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faes Farma S.A."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Given the crucial health benefits of vitamin D, addressing severe deficiencies is a pressing medical concern. This study aimed to evaluate the effectiveness and safety of two new weekly doses of calcifediol (100 \u00b5g and 125 \u00b5g) for long-term management in patients with severe vitamin D deficiency, defined as plasma 25(OH)D levels \u226410 ng\/mL. Methods: This study was a randomized, two-cohort, controlled, double-blind, multicentre phase II\u2013III trial. Subjects were randomized 2:2:1 to weekly calcifediol 100 \u00b5g, 125 \u00b5g or a placebo. The primary endpoint was the proportion of patients achieving plasma 25(OH)D levels of \u226520 ng\/mL and\/or \u226530 ng\/mL by week 16. Results: A total of 276 patients (mean age: 55.2 years, SD 15.42) were randomized. By week 16, 92.3% and 91.8% of patients in the calcifediol 100 \u00b5g and 125 \u00b5g groups, respectively, reached \u226520 ng\/mL, compared to 7.3% in the placebo group. Levels of \u226530 ng\/mL were achieved by 49% (100 \u00b5g) and 76.4% (125 \u00b5g) of participants, with none in the placebo group. Calcifediol demonstrated superior efficacy at all response levels and time points (p &lt; 0.0001). Plasma 25(OH)D concentrations increased by week 24 and remained stable. The incidence of adverse events was comparable across groups. Conclusions: A weekly calcifediol dose of 100 \u00b5g demonstrates the best profile of efficacy and tolerability, providing a reliable solution for achieving and maintaining adequate vitamin D levels in patients with severe deficiency.<\/jats:p>","DOI":"10.3390\/nu17040672","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:36:58Z","timestamp":1739443018000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Randomized Phase II\/III Trial Evaluating the Efficacy and Safety of 100 and 125 \u00b5g of Calcifediol Weekly Treatment of Severe Vitamin D Deficiency"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-217X","authenticated-orcid":false,"given":"Jose Luis","family":"P\u00e9rez-Castrill\u00f3n","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, R\u00edo Hortega University Hospital, 47012 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1234-8560","authenticated-orcid":false,"given":"Esteban","family":"J\u00f3dar-Gimeno","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Quir\u00f3n Madrid University Hospital, Universidad Europea, 28670 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1n","family":"Nociar","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital with Polyclinic Lu\u010denec n.o., 98401 Lu\u010denec, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3206-7834","authenticated-orcid":false,"given":"Michal","family":"Lojka","sequence":"additional","affiliation":[{"name":"Ordinace MediFem, s.r.o., 41501 Teplice, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitar","family":"Nikolov","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Medical Center-1-Sevlievo, 5400 Sevlievo, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Cereto-Castro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Quir\u00f3n Barcelona, 08023 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sne\u017eana","family":"Novkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute of Rheumatology, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-2189","authenticated-orcid":false,"given":"Umberto","family":"Tarantino","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, Policlinico Tor Vergata Foundation, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Mehsen-Cetre","sequence":"additional","affiliation":[{"name":"Service de Rhumatologie CHU Pellegrin-Tripode, 33000 Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Arranz","sequence":"additional","affiliation":[{"name":"Clinical Research Department, FAES FARMA, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mart\u00ednez Ostal\u00e9","sequence":"additional","affiliation":[{"name":"Clinical Research Department, FAES FARMA, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aintzane","family":"Garc\u00eda-Bea","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, FAES FARMA, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Gilaberte","sequence":"additional","affiliation":[{"name":"Clinical Research Department, FAES FARMA, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s00223-019-00559-4","article-title":"Vitamin D Deficiency: Defining, Prevalence, Causes, and Strategies of Addressing","volume":"106","author":"Cashman","year":"2020","journal-title":"Calcif. 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