{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:58:14Z","timestamp":1771459094100,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>To assess cardiac and safety parameters of iptacopan (an oral, selective, reversible, small\u2010molecule factor B inhibitor), we conducted a phase I, single ascending dose (SAD), exposure\u2013response study (A2107) instead of a traditional thorough QT study. Healthy participants were randomized 3:1 to receive a single, supratherapeutic, oral dose of iptacopan 400, 800, or 1200\u2009mg, or placebo. A2107's primary objectives were to assess iptacopan's effect on Fridericia\u2010corrected QT interval (QTcF) in a pooled analysis with the SAD phase of the first\u2010in\u2010human X2101 study, and the safety and tolerability of supratherapeutic iptacopan doses in participants. Secondary objectives included pharmacokinetics, changes in selected electrocardiogram (ECG) parameters, and categorical changes to the QTcF, PR, and QRS intervals and heart rate (pooled analysis). Thirty\u2010two participants were randomized in A2107 and 56 in X2101; demographic data were similar across treatment groups. The estimated placebo\u2010adjusted change from Day 1 baseline in QTcF at the geometric mean maximum drug concentration was 1.61 (90% confidence intervals: 0.39 to 2.82), 1.26 (\u22120.42 to 2.94), and 0.84 (\u22121.54 to 3.22) ms for 400, 800, and 1200\u2009mg doses, respectively. These primary results are consistent with no risk of QT prolongation at single, supratherapeutic, oral iptacopan doses; secondary ECG data support this conclusion. No deaths, serious adverse events (AEs), or AEs leading to study discontinuation were reported; iptacopan was overall well tolerated. A high systemic exposure of iptacopan was confirmed, allowing us to conclude that single, supratherapeutic, oral doses of iptacopan had no QTcF prolongation or proarrhythmic potential in healthy individuals.<\/jats:p>","DOI":"10.1111\/cts.70361","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:00:24Z","timestamp":1760450424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of\n                    <scp>QT<\/scp>\n                    Interval Prolongation Using Concentration\u2013\n                    <scp>QT<\/scp>\n                    Modeling for Iptacopan, an Oral Complement Factor B Inhibitor, in Healthy Individuals"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8155-8128","authenticated-orcid":false,"given":"Noemi","family":"Kaetterer","sequence":"first","affiliation":[{"name":"BioMedical Research, Novartis Pharma AG  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-3966","authenticated-orcid":false,"given":"Kenneth","family":"Kulmatycki","sequence":"additional","affiliation":[{"name":"Novartis BioMedical Research  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8520-1293","authenticated-orcid":false,"given":"Prasanna Kumar","family":"Nidamarthy","sequence":"additional","affiliation":[{"name":"Novartis Healthcare Private Limited  Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"McNamara","sequence":"additional","affiliation":[{"name":"Novartis BioMedical Research  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Armas","sequence":"additional","affiliation":[{"name":"Celerion  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkateswar","family":"Jarugula","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9896-7305","authenticated-orcid":false,"given":"Robert","family":"Schmouder","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022006960"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00028-4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018030270"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014101000"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820892116"},{"key":"e_1_2_10_7_1","first-page":"1431","article-title":"Substantial Increases in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell Clone Size With Oral Iptacopan Monotherapy Confirms Control of Hemolysis in Complement Inhibitor\u2010Naive PNH Patients","volume":"7","author":"Peffault Latour R.","year":"2023","journal-title":"HemaSphere"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000967640.29006.c9"},{"key":"e_1_2_10_9_1","unstructured":"Novartis Pharmaceuticals Corporation \u201cFABHALTA (Iptacopan) Prescribing Information \u201d2025 accessed August 1 2025 https:\/\/www.novartis.com\/us\u2010en\/sites\/novartis_us\/files\/fabhalta.pdf."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308695"},{"key":"e_1_2_10_11_1","unstructured":"ICH \u201cThe Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs. E14. Guidance for Industry \u201d2005 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S133286"},{"key":"e_1_2_10_13_1","unstructured":"ICH \u201cClinical and Nonclinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential: Questions and Answers. Guidance for Industry \u201d2022 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use."},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12128"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-179012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-179648"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2023.01.321"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2023.01.320"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad063c_4447"},{"key":"e_1_2_10_21_1","unstructured":"ICH \u201cFinal Concept Paper E14 Q&As (R3): Revision of ICH E14 Q&As (R2) \u201d2015 Guidance for industry International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use."},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad063c_4463"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","unstructured":"E.Wong C.Nester andT.Cavero \u201cIptacopan a Novel Oral Complement Alternative Pathway Factor B Inhibitor Significantly Reduces Urinary Protein Excretion and C3 Deposit Scores in Native and Transplanted Kidneys in Patients With C3 Glomerulopathy [Abstract] \u201dAmerican Society of Nephrology Kidney Week; 4\u20137 November 2021.","DOI":"10.1681\/ASN.20213210S1B8b"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T05:31:50Z","timestamp":1761370310000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/cts.70361"],"URL":"https:\/\/doi.org\/10.1111\/cts.70361","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70361"}}