{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:40:09Z","timestamp":1770486009253,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>What is known and Objective<\/jats:title><jats:p>ALO\u201002 is being developed as an abuse\u2010deterrent formulation of extended\u2010release oxycodone hydrochloride with naltrexone hydrochloride sequestered in the core of pellets contained in capsules. The primary objective of this study was to assess the effects of administration of ALO\u201002 capsule whole under fed conditions or sprinkling the pellets from ALO\u201002 capsule on applesauce under fasting conditions on the pharmacokinetics (PK) of oxycodone, naltrexone and 6\u2010\u00df\u2010naltrexol compared with ALO\u201002 capsule administered whole under fasting conditions. The plasma naltrexone and 6\u2010\u00df\u2010naltrexol concentrations were used to assess the sequestration of naltrexone in the ALO\u201002 formulation. The secondary objective was to evaluate the safety and tolerability of single 40\u2009mg doses of ALO\u201002 in healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an IRB\u2010approved, open\u2010label, single\u2010dose, randomized, 3\u2010period crossover study in 24 healthy adult volunteers, aged 18\u201355 years. Each subject was assigned to receive single 40\u2009mg doses of ALO\u201002 administered whole (intact capsule) under fasting conditions, administered whole under fed conditions (high\u2010fat breakfast \u223c 950 calories), or sprinkling the contents of the ALO\u201002 capsule (pellets) over applesauce and swallowing the dose without chewing under fasting conditions. Each treatment was separated by a 7\u2010day washout interval. Plasma samples were analyzed just before dosing through 48\u2009hours postdose for oxycodone, and through 120\u2009hours postdose for naltrexone and its major metabolite, 6\u2010\u00df\u2010naltrexol. Pharmacokinetic parameters included maximum plasma concentration [C<jats:sub>max<\/jats:sub>], area under the plasma concentration\u2010time profile from time 0 to infinity [AUC<jats:sub>inf<\/jats:sub>] and to the last quantifiable concentration [AUC<jats:sub>last<\/jats:sub>], time to C<jats:sub>max<\/jats:sub> [T<jats:sub>max<\/jats:sub>], and terminal half life [t<jats:sub>1\/2<\/jats:sub>]. Adverse events, vital signs, and laboratory parameters were monitored for safety assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The t<jats:sub>1\/2<\/jats:sub> and T<jats:sub>max<\/jats:sub> values for oxycodone were similar for all 3 treatments. There was a lack of effect of food (whole capsule, fed vs. fasted) or of sprinkling on applesauce (pellets vs. whole capsule, fasted) on oxycodone bioavailability. The Test\/Reference ratios of adjusted geometric means for oxycodone AUC<jats:sub>inf<\/jats:sub>, AUC<jats:sub>last<\/jats:sub>, and C<jats:sub>max<\/jats:sub> were 99.2%, 100%, and 107%, respectively, for the effect of food; and 101%, 101%, and 97.5%, respectively, for the effect of sprinkling on applesauce. The 90% confidence intervals contained entirely within the bioequivalence limits of 80% to 125% for each comparison. Naltrexone remained sequestered during each treatment, based on the sporadic and low measurable plasma concentrations of naltrexone and 6\u2010\u00df\u2010naltrexol. Single doses of ALO\u201002 40\u2009mg were well tolerated, and adverse events were mild, with no apparent difference in frequency for all 3 treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>What is new and Conclusion<\/jats:title><jats:p>Results indicate that ALO\u201002 can be administered without regard to food. Also, the contents of ALO\u201002 can be sprinkled over applesauce and consumed without chewing as an alternative treatment option by subjects with difficulty swallowing. Naltrexone remained sequestered in the ALO\u201002 formulation under all 3 treatments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.177","type":"journal-article","created":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T07:42:03Z","timestamp":1416469323000},"page":"370-376","source":"Crossref","is-referenced-by-count":2,"title":["Effect of food on the pharmacokinetics of oxycodone and naltrexone from ALO\u201002, an extended release formulation of oxycodone with sequestered naltrexone"],"prefix":"10.1002","volume":"4","author":[{"given":"Kuan","family":"Gandelman","sequence":"first","affiliation":[{"name":"Pfizer Inc. New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lamson","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Cary NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Salageanu","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candace","family":"Bramson","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bimal","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Pfizer Inc. New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,1,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/15360288.2012.757575"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S38562"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/15360288.2012.734905"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/00952990.2011.569623"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3810\/psm.2012.11.1975"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(96)00300-4"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(96)80182-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1992.tb04090.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700222011238"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/J354v18n04_03"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.01.009"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90024-7"},{"key":"e_1_2_9_14_1","unstructured":"Naltrexone Hydrochloride (naltrexone hydrochloride USP) Tablet Prescribing Information Revised January 2003. Barr Laboratories Inc.http:\/\/dailymed.nlm.nih.gov\/dailymed\/about.cfm(accessed 24 June 2010)."},{"key":"e_1_2_9_15_1","unstructured":"Food and Drug Administration. 2002 Guidance for Industry: Food\u2010Effect Bioavailability and Fed Bioequivalence Studies. December2002.http:\/\/www.fda.gov\/downloads\/regulatoryinformation\/guidances\/ucm126833.pdf(assessed 22 October 2013)."},{"key":"e_1_2_9_16_1","unstructured":"Roxicodone\u00ae (oxycodone hydrochloride) Tablet Prescribing Information Revised March 2009. Xanodyne Pharmaceuticals Inc.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2009\/021011s003lbl.pdf(accessed 8 October 2014)."},{"key":"e_1_2_9_17_1","unstructured":"Revia\u00ae (naltrexone hydrochloride USP) Tablet Prescribing Information Revised October 2003. D Uramed Pharmaceuticals Inc.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2013\/018932s017lbl.pdf(accessed 7 October 2014)."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140030-00006"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.177","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T13:11:05Z","timestamp":1696597865000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,22]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1002\/cpdd.177"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.177","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,22]]}}}