{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:07:39Z","timestamp":1768475259777,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T00:00:00Z","timestamp":1523318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Reviva Pharmaceuticals, Inc."},{"name":"PAREXEL International from Reviva Pharmaceuticals, Inc"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>RP5063 is a multimodal dopamine (D)\u2010serotonin (5\u2010HT) stabilizer with a high affinity for D<jats:sub>2\/3\/4<\/jats:sub> and 5\u2010HT<jats:sub>1A\/2A\/2B\/7<\/jats:sub> receptors and moderate affinity for the serotonin transporter. Single\u2010dose (10 and 15 mg fasting, 15 mg fed) safety in healthy volunteers and multiple\u2010dose (10, 20, 50, and 100 mg fed, 10 days) safety and pharmacodynamics in patients with stable schizophrenia were defined in two phase I studies. In the single\u2010dose study, 32 treatment\u2010emergent adverse events (TEAEs) were observed. Orthostatic hypotension (<jats:italic>n<\/jats:italic> = 6), nausea (<jats:italic>n<\/jats:italic> = 5), and dizziness (<jats:italic>n<\/jats:italic> = 4) were the most common. One serious adverse event (SAE), seen in a patient who should not have been in the study due to a history of seizures, involved brief seizure\u2010like symptoms. In the multiple\u2010dose study, 75 TEAEs were reported. Akathisia (<jats:italic>n<\/jats:italic> = 20) and somnolence (<jats:italic>n<\/jats:italic> = 14) were the most frequent. No clinically significant changes were seen in glucose or prolactin levels, lipid profiles, weight, or electrocardiographic recordings. In both studies, all TEAEs resolved and none led to withdrawal from the study or death. A pharmacodynamic evaluation reflected significant improvements with RP5063 (<jats:italic>P<\/jats:italic> &lt; 0.05) over placebo in an analysis of patients with a baseline Positive and Negative Syndrome Scale (PANSS) score \u226550 for positive subscale scores. Improvements of the Trail Making A and Trail Making B test results were observed for patients treated in the 50 mg dose group for days 5, 10, and 16. These findings indicate that RP5063 is well\u2010tolerated up to 100 mg and displays promising preliminary clinical behavioral and cognition activity signals in patients with stable disease over a 10\u2010day period.<\/jats:p>","DOI":"10.1111\/cts.12545","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:46:12Z","timestamp":1523407572000},"page":"387-396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia"],"prefix":"10.1111","volume":"11","author":[{"given":"Marc","family":"Cantillon","sequence":"first","affiliation":[{"name":"Reviva Pharmaceuticals, Inc.  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