A phase III, randomized, double-blind, placebo- controlled study of the safety and efficacy of lofexidine for relief of symptoms in adults undergoing inpatient opioid detoxification

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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226

Has nicotine dependence increased among smokers in the United States? A new test of the hardening hypothesis Renee Goodwin 1,2,∗ , Melanie Wall 3 , Sandro Galea 5 , Michael J. Zvolensky 4 , Misato Gbedemah 1 , Mei-Chen Hu 6 , Deborah S. Hasin 2 1

Psychology, City University of New York, Queens, NY, United States 2 Epidemiology, Columbia University, New York, NY, United States 3 Biostatistics, Columbia University, New York, NY, United States 4 Psychology, University of Houston, Houston, TX, United States 5 Epidemiology, Boston University, Boston, MA, United States 6 Sociomedical Sciences, Columbia University, New York, NY, United States Aims: The Hardening Hypothesis posits that one reason for the slowed smoking decline in recent years is an increasing prevalence of nicotine dependence among remaining smokers. The current study evaluated trends in cigarette smoking and the prevalence of nicotine dependence among smokers from 2003 to 2013. Methods: Data were drawn from the National Household Survey on Drug Use (NSDUH), an annual cross-sectional study of U.S. persons ages 12 and over (N = ∼52,000–58,000 per year). Nicotine dependence was examined annually from 2003 to 2013. Linear time trend analyses were then adjusted for age, gender, income, and number of cigarettes smoked per day among current daily and non-daily smokers. Results: Unadjusted estimates suggest that the prevalence of nicotine dependence declined among daily smokers and remained relatively unchanged among non-daily smokers from 2003 to 2013. However, after adjusting for demographics and number of cigarettes smoked per day, a significant increase in the prevalence of nicotine dependence is evident among both daily and non-daily smokers from 2003 to 2013. Conclusions: This study provides new information supporting the hardening hypothesis with empirical, population-based data, using an approach that examines prevalence of nicotine dependence while accounting separately for the changing number of cigarettes smoked per day and demographic changes among smokers from 2003–2013. In order for tobacco control efforts to make further progress in bringing the prevalence lower, our results suggest that treatment of nicotine dependence, in addition to smoking cessation efforts, needs to be made widely available. Financial support: This work was supported by NIDA grant #DA20892 (Goodwin). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.216

A phase III, randomized, double-blind, placebocontrolled study of the safety and efficacy of lofexidine for relief of symptoms in adults undergoing inpatient opioid detoxification Charles Gorodetzky 1,∗ , Sharon L. Walsh 2 , Kristen Gullo 3 1

USWM (Cons.), Kansas City, MO, United States University KY, Lexington, KY, United States 3 USWM, Louisville, KY, United States 2

Aims: This study investigated the safety and efficacy of LFX, an ␣-2 receptor agonist, in reducing withdrawal symptoms in adults undergoing opioid detoxification. Methods: This was a 1-week inpatient, multicenter, randomized, double-blind, placebo-controlled study in adults dependent on short-acting opioids. Subjects were randomized in a 1:1 ratio to receive LFX (0.8 mg QID) (n = 134) or placebo (n = 130) for 5 days, followed by 2 days of blinded PBO, with study discharge on Day 8. The co-primary efficacy endpoints were the mean SOWS-Gossop (SOWS-G) score on Day 3 of withdrawal and time to dropout. A key secondary endpoint was the proportion of subjects who completed the 5-day treatment period. Results: The mean Day 3 SOWS-G score was 2.4 points higher with PBO than with LFX and was statistically significant with (p = .0212) and without (p = .0136) imputation of missing data. Fewer subjects on LFX (n = 59) were early terminators than those on PBO (n = 80); and subjects who dropped out early stayed longer in the trial if they were taking LFX (p = .0034). The proportion of subjects who completed the 5-day detoxification was higher when on LFX (49%) than when on PBO (33%) (p = .0087). Overall 97% of LFX subjects and 94% of PBO subjects reported adverse events with most judged to be withdrawal-related. AEs significantly higher on LFX than on PBO were hypotension, dizziness, dry mouth and bradycardia. These did not require therapeutic intervention. Serious AEs occurred in 16 subjects (8/group). No SAEs were life threatening or led to death and all resolved rapidly without sequelae. There was no evidence of QTc prolongation in safety ECGs and there were no clinically significant changes in other ECG intervals. Conclusions: LFX reduced the subjective severity of opioid withdrawal and led to superior retention compared to PBO. These data suggest that LFX provides a safe and effective non-narcotic treatment option for patients undergoing acute withdrawal from opioids. Financial support: Supported by US WorldMeds, LLC. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.217 Extinction and reinstatement of cocaine-reinforced behavior in rat lines selected for low and high levels of intravenous drug self-administration Ken Grasing ∗ , Haiyang Xu Kansas City VA Medical Center, Kansas City, MO, United States Aims: The LS and HS rat strains were developed in our laboratory through selective breeding for Low- and High-levels of intravenous drug Self-administration. HS rats self-administer cocaine at higher levels than LS animals, and exhibit greater cocaine-induced activation dopaminergic neurons in the accumbens. This study was undertaken to compare extinction and reinstatement behavior in the two strains. Methods: Following six generations of selective breeding, LS and HS lines were inbred for an additional 10 generations. Current