Charles W Gorodetzky1, Sharon L Walsh2, Peter R Martin3, Andrew J Saxon4, Kristen L Gullo5, Kousick Biswas6. 1. Consultant in Pharmaceutical Medicine, 433 Ward Parkway, Unit 6S, Kansas City, MO, 64112, USA. Electronic address: cgoro@kc.rr.com. 2. Center on Drug and Alcohol Research, Department of Behavioral Science, University of Kentucky College of Medicine, 845 Angliana Avenue, Lexington, KY, 40508, USA. 3. Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, 1601 23rd Avenue South, Suite 3068, Nashville, TN, 37232, USA. 4. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and VA Puget Sound Health Care System, 1660 S Columbian Way, S-116 Atc, Seattle, WA, 98108, USA. 5. US WorldMeds, LLC. 4441 Springdale Rd, Louisville, KY, 40241, USA. 6. Cooperative Studies Program Coordinating Center (CSPCC), U.S. Department of Veterans Affairs, Perry Point, MD, 21902, USA.
Abstract
BACKGROUND:Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. METHODS: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy oflofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC1-5), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. RESULTS:Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. CONCLUSION:Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms.
RCT Entities:
BACKGROUND:Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. METHODS: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC1-5), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. RESULTS:Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidinepatients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. CONCLUSION:Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms.
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