{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T14:55:16Z","timestamp":1707490516463},"reference-count":12,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tebipenem pivoxil hydrobromide (TBP\u2010PI\u2010HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP\u2010PI\u2010HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open\u2010label, randomized, single\u2010dose, three\u2010sequence, four\u2010period crossover, BE, and food\u2010effect study. Subjects received single 600\u2009mg oral doses of TBP\u2010PI\u2010HBr as the reference clinical trial tablet (treatment A) and test registration tablet (treatment B) formulations in alternating sequence while fasting, and then the test formulation under fed conditions. Whole blood samples were collected predose and at specified intervals up to 24\u00a0h postdose to evaluate TBP PK parameters. Safety and tolerability were monitored. Thirty\u2010six healthy, adult subjects were enrolled and completed the study. The criteria for BE were met for the TBP\u2010PI\u2010HBr test (registration tablet) and reference (clinical trial tablet) formulations as the 90% confidence intervals for the geometric mean ratios for TBP area under the curve (AUC)<jats:sub>0\u2010<jats:italic>t<\/jats:italic><\/jats:sub>, AUC<jats:sub>0\u2010inf<\/jats:sub>, and maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) fell within the established 80% to 125% BE limits. Dosing with food had no meaningful effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of mild severity. No deaths, serious AEs, or discontinuations due to AEs were reported, and no clinically relevant electrocardiograms, vital signs, or safety laboratory findings were observed. The study results demonstrate the BE of oral TBP\u2010PI\u2010HBr registration and clinical trial tablet formulations and indicate that TBP\u2010PI\u2010HBr can be administered without regard to meals.<\/jats:p>","DOI":"10.1111\/cts.13280","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T06:03:52Z","timestamp":1649743432000},"page":"1654-1663","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects"],"prefix":"10.1111","volume":"15","author":[{"given":"Vipul K.","family":"Gupta","sequence":"first","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Patel","sequence":"additional","affiliation":[{"name":"Patel Kwan Consultancy LLC  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne","family":"Gasink","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floni","family":"Bajraktari","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Lei","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akash","family":"Jain","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praveen","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela K.","family":"Talley","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2018.1496821"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00618-19"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105462"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00145-21"},{"key":"e_1_2_9_6_1","unstructured":"PatelG RodvoldKA GuptaVK et al.Pharmacokinetics of oral tebipenem pivoxil hydrobromide in subjects with varying degrees of renal impairment. Abstract #00660 presented at the 2021 European Congress of Clinical Microbiology and Infectious Diseases July 9\u201312 2021."},{"key":"e_1_2_9_7_1","unstructured":"Food and Drug Administration: Center for Drug Evaluation and Research (CDER).Guidance for Industry: Assessing the Effects of Food on Drugs in INDs and NDAs \u2014 Clinical Pharmacology Considerations (Draft Feb 2019).https:\/\/www.fda.gov\/media\/121313\/download"},{"key":"e_1_2_9_8_1","unstructured":"Food and Drug Administration: Center for Drug Evaluation and Research (CDER).Guidance for Industry: Bioavailability Studies Submitted in NDAs or INDs\u2014General Considerations (Draft Guidance February 2019).https:\/\/www.fda.gov\/media\/121311\/download\/"},{"key":"e_1_2_9_9_1","unstructured":"SrivastavaP ManyakE UtleyL GuptaV.A validated sensitive and selective Ultra\u2010High Performance Liquid Chromatography\u2010Tandem Mass Spectrometry (UPLC\u2010MS\/MS) method for quantitative analysis of tebipenem pivoxil and tebipenem in Human Whole Blood and its Application in a Pharmacokinetic Study in Healthy Human Volunteers. Poster presented at the 15th WRIB Virtual Meeting Sept. 27\u2010Oct. 1 2021."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9406-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-008-9053-4"},{"key":"e_1_2_9_12_1","unstructured":"JohnsonA FarringtonN McEnteeL et al.Pharmacokinetics and pharmacodynamics of tebipenem (SPR859) for multi\u2010drug resistant Enterobacteriaceae in a hollow fibre infection model. Poster #L2 presented at ESCMID ASM 4\u20137 September 2018 Lisbon Portugal."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.9.1.23"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13280","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13280","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T19:17:41Z","timestamp":1694891861000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/cts.13280"],"URL":"https:\/\/doi.org\/10.1111\/cts.13280","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"assertion":[{"value":"2021-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}