Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell？)

Three pharmacokinetic (PK), one safety and two efficacy studies were carried out with Nicotinell lozenges. PK trials were: (1) a single-dose, three-way crossover study comparing 1 and 2 mg lozenges with 2 mg nicotine gum; (2) a multiple-dose, two-way crossover study comparing 1 mg lozenge with 2 mg gum; (3) a multiple-dose, three-way crossover study comparing 1 and 2 mg lozenges with 4 mg gum. Safety trial: (4) a single dose study to assess the safety of swallowing up to 12 lozenges containing 1 mg nicotine. Efficacy trials: two efficacy studies in (5) France and (6) the USA, including more than 900 smokers followed-up for up to one year, conducted with the 1 mg lozenge.The results of the individual PK trials showed that the 1 mg Nicotinell lozenge is bioequivalent to 2 mg polacrilex gum, as demonstrated by similar blood PK parameters (tmax, Cmax, AUC). The 2 mg lozenge was found to deliver quantities of nicotine that were intermediate between those delivered by 2 and 4 mg polacrilex gum.The short-term efficacy of the 1 mg lozenge in comparison with placebo was also demonstrated with significantly more subjects continuously abstinent from smoking with active lozenges on week 6 in two different populations: moderate to heavy smokers (FTND between 4 and 7) OR = 1.72 [95% CI: 1.05–2.80]; heavy to very heavy smokers (FTND 6 and over) OR = 2.87 [95% CI: 1.18–6.97].Nicotinell lozenges were found to be safe with mainly mild and reversible adverse events. The safety of the 1 mg lozenge formulation, even when misused was also demonstrated.The data presented in this review demonstrate high nicotine bioavailability, excellent safety profile and proven short-term efficacy of Nicotinell lozenges. At nominal equivalent doses 1 and 2 mg Nicotinell lozenges were shown to deliver larger amounts of bioavailable nicotine compared to the nicotine polacrilex gum. According to the data developed here, the systemic exposure to nicotine could be ranked: 4 mg polacrilex gum > 2 mg Nicotinel