{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:18:08Z","timestamp":1783333088635,"version":"3.54.6"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Uterine fibroids are the most common benign gynecological tumors, often causing heavy menstrual bleeding (HMB), anemia, and impaired quality of life. A fixed\u2010dose combination (FDC) of relugolix (40\u00a0mg), estradiol (1\u00a0mg), and norethindrone acetate (0.5\u00a0mg) was developed to address these limitations. This open\u2010label, randomized, two\u2010treatment, two\u2010sequence, four\u2010period, crossover bioequivalence study was conducted in 48 healthy postmenopausal women under fasting conditions. Participants received a single oral dose of either the RELUEASE (Sun Pharmaceutical Industries Limited, India) or the reference product (MYFEMBREE) (Patheon Inc., Mississauga, Ontario), with a 21\u2010day washout. Pharmacokinetics parameters were derived using non\u2010compartmental analysis. Bioequivalence assessment was performed using a linear mixed\u2010effects model applied to ln\u2010transformed pharmacokinetic parameters. A total of 39 participants completed all study periods. The point estimates and 90% confidence intervals (CIs), or the 95% upper bound for the pharmacokinetic parameters (C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC) of relugolix, estradiol, norethindrone, and estrone met the predefined bioequivalence acceptance criteria. Six adverse events were reported, all mild, transient in nature, and resolving without sequelae. No clinically significant safety concerns were observed during the study. The relugolix\/estradiol\/norethindrone acetate FDC demonstrated bioequivalence to the globally approved reference product (MYFEMBREE) with comparable tolerability. This provides a safe, effective, reversible non\u2010surgical therapy for fibroid\u2010related HMB, fulfilling an unmet need beyond surgery.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70076","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:30:30Z","timestamp":1781875830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioequivalence of a Fixed\u2010Dose Combination of Relugolix, Estradiol, and Norethindrone Acetate: An Open\u2010Label, Randomized, Fully Replicate Crossover Study in Healthy Postmenopausal Women Under Fasting Conditions"],"prefix":"10.1002","volume":"15","author":[{"given":"Ravi","family":"Kotadia","sequence":"first","affiliation":[{"name":"Medical Affairs and Clinical Research Sun Pharma Laboratories Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudershan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Pharmacokinetics CPP Sun Pharmaceutical Industries Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Khuroo","sequence":"additional","affiliation":[{"name":"Pharmacokinetics CPP Sun Pharmaceutical Industries Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Dharmadhikari","sequence":"additional","affiliation":[{"name":"Medical Affairs and Clinical Research Sun Pharma Laboratories Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Shahi","sequence":"additional","affiliation":[{"name":"Pharmacokinetics CPP Sun Pharmaceutical Industries Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goru N. V. S. Satya","family":"Narayana","sequence":"additional","affiliation":[{"name":"Pharmacokinetics CPP Sun Pharmaceutical Industries Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simrit","family":"Reyar","sequence":"additional","affiliation":[{"name":"Pharmacokinetics CPP Sun Pharmaceutical Industries Ltd. India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03622-9"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.99"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1209993"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S51083"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2017.1372107"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914735"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2016.04.001"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmw023"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904351"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2012.07.018"},{"issue":"2","key":"e_1_2_12_12_1","article-title":"Combined hormonal contraceptives for heavy menstrual bleeding","volume":"2","author":"Lethaby A","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_13_1","article-title":"Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis","volume":"16","author":"Ferreira JCA","year":"2022","journal-title":"Ther Adv Reprod Health"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2008283"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000004988"},{"key":"e_1_2_12_16_1","volume-title":"Myfembree (relugolix, estradiol, norethindrone acetate) prescribing information","author":"U.S. Food and Drug Administration","year":"2021"},{"key":"e_1_2_12_17_1","volume-title":"Ryeqo (relugolix, estradiol, norethisterone acetate) European public assessment report (EPAR)","author":"European Medicines Agency","year":"2021"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.07.013"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.07.013"},{"issue":"1","key":"e_1_2_12_20_1","first-page":"34","article-title":"Appearance of double peaks in plasma concentration\u2010time profile after oral administration depends on gastric emptying profile and weight function","volume":"23","author":"Sako Y","year":"2008","journal-title":"Drug Metab Pharmacokinet"},{"issue":"18","key":"e_1_2_12_21_1","first-page":"1911","article-title":"Relugolix: a review in advanced prostate cancer","volume":"82","author":"Markham A","year":"2022","journal-title":"Drugs"},{"key":"e_1_2_12_22_1","unstructured":"European Medicines Agency.Orgovyx (relugolix): EPAR \u2010 Product Information [Internet].2022[cited 2024 May 22]. Available from:europa.eu"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.874973"},{"key":"e_1_2_12_24_1","unstructured":"Sun Pharmaceutical Industries Limited.A prospective randomized multi\u2010center parallel\u2010group assessor\u2010blind active\u2010controlled Phase III study to assess the efficacy and safety of relugolix estradiol and norethindrone acetate in women with heavy menstrual bleeding associated with uterine fibroids (REEMEMBER). Clinical Trial Registry of India: CTRI\/2024\/06\/068615. Registered on June 10 2024."}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70076","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70076","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:55:04Z","timestamp":1783331704000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/cpdd.70076"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70076","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70076"}}