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As with other TLR7 agonists, the study drug\u2010related adverse events of flu\u2010like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)\/pharmacodynamic (PD) and flu\u2010like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC\u2010suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod. Linear and logistic regression were used to explore potential relationships between dose, flu\u2010like symptoms, PK, and PD. Generalized linear regression was performed to predict the probability of flu\u2010like symptoms of all intensities at different RO7011785 (the active metabolite of the double prodrug ruzotolimod) PK exposure. This analysis showed that single or multiple doses of ruzotolimod at \u2a7e100\u2009mg, the immune PD (IFN\u2010\u03b1, neopterin, IP\u201010, and the transcriptional expression of ISG15, OAS\u20101, MX1, and TLR7) responses increase with the RO7011785 PK exposure, which increases linearly with the doses from 3\u2009mg to 170\u2009mg of ruzotolimod. The analysis also showed that the probability of flu\u2010like symptoms occurrence increases with PD responses (IFN\u2010\u03b1 and IP\u201010). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug\u2010related flu\u2010like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu\u2010like symptoms.<\/jats:p>","DOI":"10.1111\/cts.13896","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T11:43:00Z","timestamp":1723203780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu\u2010like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll\u2010like receptor 7 agonist ruzotolimod"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2351-145X","authenticated-orcid":false,"given":"Qiudi","family":"Jiang","sequence":"first","affiliation":[{"name":"Roche Innovation Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Duan","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-8438","authenticated-orcid":false,"given":"Sylvie","family":"Retout","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Upmanyu","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Welwyn UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-8781","authenticated-orcid":false,"given":"Katerina","family":"Glavini","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7991-6916","authenticated-orcid":false,"given":"Miriam","family":"Triyatni","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0858-1506","authenticated-orcid":false,"given":"Yonghong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Grippo","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4532-1988","authenticated-orcid":false,"given":"Yuyan","family":"Jin","sequence":"additional","affiliation":[{"name":"Roche Innovation Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.Hepatitis B. 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