{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T07:53:52Z","timestamp":1775289232939,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T00:00:00Z","timestamp":1547683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Olas Pharma, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5\u2009mg) with hydrocodone 7.5\u2009mg\/acetaminophen 325\u2009mg (HC\/APAP) was used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC\/APAP, or placebo. Over the next 24\u2009hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24\u2009hours (SPID24).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Relative to HC\/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P\u2009&amp;lt;\u20090.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P\u2009&amp;lt;\u20090.001). There were no unexpected or serious adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CL-108 is a safe and effective combination analgesic\/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/pm\/pny294","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T23:24:10Z","timestamp":1543447450000},"page":"2528-2538","source":"Crossref","is-referenced-by-count":3,"title":["Prevention of Opioid-Induced Nausea and Vomiting During Treatment of Moderate to Severe Acute Pain: A Randomized Placebo-Controlled Trial Comparing CL-108 (Hydrocodone 7.5 mg\/Acetaminophen 325 mg\/Rapid-Release, Low-Dose Promethazine 12.5 mg) with Conventional Hydrocodone 7.5 mg\/Acetaminophen 325 mg"],"prefix":"10.1093","volume":"20","author":[{"given":"John R","family":"Zuniga","sequence":"first","affiliation":[{"name":"Department of Surgery and Division of Oral and Maxillofacial Surgery, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athena S","family":"Papas","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Tufts School of Dental Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen E","family":"Daniels","sequence":"additional","affiliation":[{"name":"Optimal Research, LLC, Austin, Texas"},{"name":"Formerly with Premier Research Group, LLC, Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Patrick","sequence":"additional","affiliation":[{"name":"PRA Health Sciences, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek D","family":"Muse","sequence":"additional","affiliation":[{"name":"Jean Brown Research, Inc., Salt Lake City, Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Oreadi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Tufts School of Dental Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen E","family":"Giannakopoulos","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J","family":"Granquist","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence M","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joli C","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilda","family":"Maibach","sequence":"additional","affiliation":[{"name":"IndigoRDD, LLC, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard P","family":"Schachtel","sequence":"additional","affiliation":[{"name":"Olas Pharma, Inc. 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