{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:53:57Z","timestamp":1783090437768,"version":"3.54.6"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CIN\u2010102 is a deuterated form of domperidone in development for the treatment of acute, recurrent gastroparesis. This thorough QT study assessed the effects of CIN\u2010102 on cardiac repolarization in 62 healthy volunteers. In this 4\u2010period randomized crossover study, participants were administered single doses of 30\u2010mg CIN\u2010102 (representing therapeutic exposures), 100\u2010mg CIN\u2010102 (representing supratherapeutic exposures), placebo, and moxifloxacin (positive control). Continuous 12\u2010lead electrocardiograms (ECGs) and time\u2010matched blood samples were collected to determine plasma levels of deuterated domperidone and its major metabolites. The primary endpoint was placebo\u2010corrected change\u2010from\u2010baseline QTc corrected by Fridericia's formula (\u0394\u0394QTcF). By\u2010time\u2010point and concentration\u2010QTc analyses excluded an effect on \u0394\u0394QTcF exceeding 10 ms for both doses of CIN\u2010102 at all time points up to deuterated domperidone plasma concentrations of \u224892\u200a ng\/mL (\u22486 times the therapeutic steady\u2010state concentration). There were no clinically relevant effects of CIN\u2010102 on heart rate or cardiac conduction, and no deaths or serious adverse events occurred. This thorough QT study demonstrated that at doses producing therapeutic and supratherapeutic exposures, CIN\u2010102 does not have a clinically meaningful effect on ECG parameters, including QT interval. This modified formulation of domperidone provides a potential gastroparesis treatment while decreasing the risk of QT prolongation associated with the traditional formulation of domperidone.<\/jats:p>","DOI":"10.1002\/cpdd.70039","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:41:03Z","timestamp":1773049263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Results of a Phase 1 Study Assessing the Effect of CIN\u2010102, a Novel Formulation of the Dopamine Receptor Antagonist Domperidone Designed to Treat Gastroparesis, on Cardiac Repolarization in Healthy Volunteers"],"prefix":"10.1002","volume":"15","author":[{"given":"Mary","family":"Bond","sequence":"first","affiliation":[{"name":"CinDome Pharma, Inc.  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Murphy","sequence":"additional","affiliation":[{"name":"CinDome Pharma, Inc.  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Doran","sequence":"additional","affiliation":[{"name":"CinDome Pharma, Inc.  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borje","family":"Darpo","sequence":"additional","affiliation":[{"name":"Clario  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqi","family":"Xue","sequence":"additional","affiliation":[{"name":"Clario  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Vrishabhendra","sequence":"additional","affiliation":[{"name":"Medpace, Inc.  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Isaacsohn","sequence":"additional","affiliation":[{"name":"CinDome Pharma, Inc.  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2010.09.022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0134-4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.047"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2012.18.1.34"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.373"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(09)67010-5"},{"key":"e_1_2_10_8_1","unstructured":"How to request domperidone for expanded access use. U.S. Food and Drug Administration. Accessed August 10 2022.https:\/\/www.fda.gov\/drugs\/investigational\u2010new\u2010drug\u2010ind\u2010application\/how\u2010request\u2010domperidone\u2010expanded\u2010access\u2010use"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.14309\/01.ajg.0000703940.85438.74"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.18003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.126"},{"issue":"5","key":"e_1_2_10_12_1","first-page":"457","article-title":"Domperidone, a new dopamine antagonist","volume":"135","author":"Champion MC","year":"1986","journal-title":"CMAJ"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04093.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00578-X"},{"issue":"1416","key":"e_1_2_10_15_1","first-page":"66","article-title":"Domperidone safety: a mini\u2010review of the science of QT prolongation and clinical implications of recent global regulatory recommendations","volume":"128","author":"Buffery PJ","year":"2015","journal-title":"N Z Med J"},{"key":"e_1_2_10_16_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. U.S. Food and Drug Administration Guidance for Industry. E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs. October2005."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-017-4456-7"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.04.011"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31827afd0d"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-818586-5.00025-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001485"},{"issue":"4","key":"e_1_2_10_22_1","first-page":"001","article-title":"Deuteration as a tool for optimization of metabolic stability and toxicity of drugs","volume":"1","author":"Kaur S","year":"2017","journal-title":"Glob J Pharmaceu Sci"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000083234"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.16.1883"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2137"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2165\/11634300-000000000-00000"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:48:16Z","timestamp":1774360096000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/cpdd.70039"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70039","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70039"}}