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Background Nicotine replacement therapy (NRT) has been demonstrated to be an effective pharmacological treatment for smoking cessation, and most types of NRT have been approved as over-the-counter (OTC) medications. In an effort to create a fast-acting, flexible, and discreet NRT, a nicotine mouth spray (NMS) has been developed. This study was designed to assess the efficacy and safety of NMS in a naturalistic setting in the United States. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 26-week study in 1198 smokers motivated to quit. The study was designed to resemble an OTC environment, and thus included limited intervention, limited motivational screening, and no behavioral support. The primary efficacy endpoint was carbon monoxide-verified, self-reported continuous abstinence from smoking from week 2 until week 6. The safety of NMS was assessed by measuring vital signs, visual mouth inspection, and collection of subject-reported adverse events (AEs). Results The percentage of subjects with carbon monoxide-verified continuous abstinence from week 2 to week 6 was statistically significantly greater in the NMS group compared with the placebo group (5.0% vs. 2.5%, p = .021). Statistically significant treatment effects for the NMS were maintained throughout the 26-week period. The study medications were generally well tolerated. The severity of AEs was similar for both treatment groups, and most AEs were of mild or moderate severity. Conclusions These study results demonstrate that the NMS is an effective and safe smoking cessation option for smokers motivated to quit, even in a naturalistic setting and without behavioral support. Implications This study demonstrated the safety, efficacy, and acceptability of an NMS in an OTC environment with no behavioral counseling or support. It provides an additional option for smokers motivated to quit. Trial registration ClinicalTrials.gov (number NCT02355665).

Introduction A new law in the United States gives the Food and Drug Administration (FDA) wide latitude to regulate tobacco products for the first time. Given the need for science to serve as a foundation for FDA actions, it is critical that a scientific review of the literature relevant to the proposed legislation be undertaken by experts in the field of nicotine and tobacco research in order to develop research priorities. Methods This paper describes an initiative that was implemented to identify research opportunities under "The Family Smoking Prevention and Tobacco Control Act" and summarizes the conclusions and future directions derived from that initiative. Results Multiple research and surveillance needs were identified, such as characterization of biomarkers and increased analysis of risk perception. It was also recognized that science will play a critical role in policy determinations such as what constitutes "substantial equivalence" and that there will be considerable infrastructure needs (e.g., laboratories for product testing). Conclusions Science must drive FDA's decision making regarding tobacco regulation. This article provides a summary of research opportunities identified through literature reviews related to various provisions of the new law. However, the science required by the law requires a transdisciplinary approach because of its complexity, so one of the challenges facing the FDA will be to connect the silos of research in recognition that the "system" of tobacco regulation is greater than the sum of its parts.

Many smokers are not ready to quit but are interested in changing their smoking behavior, particularly if such a change is associated with a reduction in health risk. The present study evaluated the efficacy of the nicotine inhaler in reducing smoking. Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk. A total of 429 healthy smokers (smoking at least 20 cigarettes/day) were randomly assigned to either nicotine-containing or placebo inhalers, which subjects were allowed to use ad libitum for up to 1 year. The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50% after 4 months, compared with baseline (18% vs. 8%, p = .004). Active treatment promoted smoking cessation: 8% of subjects in the nicotine group and 1% in the placebo group were abstinent at month 15. Throughout the study, smoking reduction, per se, independent of treatment group, was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate. Smoking reduction also improved established risk markers for cardiovascular disease over 4 months. The incidence of adverse events did not differ significantly between the active and placebo groups. The most common treatment-related adverse events were throat irritation and cough. In conclusion, the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption, which may be a health benefit on its own and may further promote quitting.

Some studies have shown that female smokers and smokers with a history of depression have an increased risk of relapse following smoking cessation treatment. This study examined the efficacy of bupropion sustained-release (SR) and the nicotine patch for smoking cessation in subgroups of smokers at possible risk for relapse. Data for this study were from a previously published randomized, double-blind, placebo-controlled clinical trial in which 893 smokers were randomized to four treatment conditions: placebo tablet + placebo patch, placebo tablet + 21 mg/24-hr nicotine patch, 300mg bupropion SR + placebo patch, and 300mg bupropion SR + 21 mg/24-hr nicotine patch. Study medication continued for 8 weeks after the quit day; brief individual cessation counseling was provided during weekly clinic visits. In comparison to the placebo tablet, bupropion SR approximately tripled 1-year non-smoking rates among women and previously depressed individuals. In contrast, the nicotine patch did not significantly improve cessation rates for any group. We conclude that bupropion SR is a first-line treatment for smoking that has the potential to benefit all smokers, especially women and the previously depressed.

This study determined whether higher dose nicotine patches are more efficacious than lower dose patches among heavy smokers. A randomized double-blind study compared 0, 21, 35, and 42 mg/day of a 24-h patch in 1039 smokers (> or = 30 cigarettes/day) at 12 clinical sites in the USA and one in Australia. Daily patches were used for 6 weeks followed by tapering over the next 10 weeks. Weekly group therapy occurred. Biochemically validated self-reported quit rates at 6, 12, 26, and 52 weeks post-cessation were measured. Quit rates were dose-related at all follow-ups (p < 0.01). Continuous, biochemically verified abstinence rates for the 0, 21, 35, and 42 mg doses at the end of treatment (12 weeks) were 16, 24, 30, and 39%. At 6 months, the rates were 13, 20, 20, and 26%. Among the 11 sites with 12 month follow-up (n = 879), the quit rates were 7, 13, 9, and 19%. In post-hoc tests, none of the active doses were significantly different from each other at any follow-up. The rates of dropouts due to adverse events for 0, 21, 35, and 42 mg were 3, 1, 3, and 6% (p = n.s.). Our results are similar to most prior smaller studies; i.e., in heavy smokers higher doses increase quit rates slightly. Longer durations of treatment may be necessary to show greater advantages from higher doses.