To examine the abuse liability (AL) of two mint-flavored hard and soft dissolvable nicotine lozenges (NL), we conducted a two-arm, five-way crossover study in confinement with healthy smokers. Subjects participated in five daily test sessions (each following a 12-hour minimum nicotine abstinence period) with randomized use of one of five products each session: usual brand combustible cigarette (CC / high-AL comparator), nicotine replacement therapy lozenge (NRT / low-AL comparator), one NL, or simultaneous use of two or four NLs. Results of subjective measures and nicotine pharmacokinetic parameters after use of NLs were compared with results after use of the high and low-AL comparators. Blood samples, subjective measures, vital signs, and adverse events (AEs) were collected over the course of 6 hours prior to, during, and following product use.

Results demonstrated that total nicotine uptake over 6 hours (AUC0-360min) was statistically significantly lower for a single NL than for either CC or NRT. AUC0-360min after use of two and four NLs was similar to or higher than for CC or NRT. Mean scores for several product liking subjective measures were statistically significantly lower for all NLs compared to CC and not different from NRT. The mean scores for “positive effects” after use of all NLs were generally similar to those for NRT, however, mean scores for “negative effects” increased with the number of lozenges used simultaneously. Mild AEs such as hiccups, nausea, and throat irritation were similar among NLs and NRT, and for the NLs, increased with increasing number of lozenges. Results demonstrate that these NLs have AL profiles less than CC and similar to NRT lozenge and suggest that they have a low risk of abuse.