Pamela M Lai1, Mako Araga2, Ana Hamilton2, Marianna Armogida3. 1. GlaxoSmithKline, 184 Liberty Corner Road, Ste 200, Warren, NJ, 07059, USA. pamela.m.lai@gsk.com. 2. GlaxoSmithKline, 184 Liberty Corner Road, Ste 200, Warren, NJ, 07059, USA. 3. GlaxoSmithKline, Route de l'Etraz 2, Case postale, 1260, Nyon 1, Switzerland.
Abstract
INTRODUCTION: Cigarette smoking remains a substantial public health problem. Nicotine replacement therapy (NRT) is an effective treatment that increases the success of a quit attempt. There are different NRT formats with no difference in efficacy, but their pharmaceutical form or route of administration may translate into individual preferences. A novel prototype mini lozenge was developed to offer smokers a new NRT option to aid in their quit attempt. Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge. METHODS: Two randomized, open-label, crossover studies were conducted to evaluate either the 2 or 4 mg dose level. Heavy smokers in otherwise good health were randomly assigned to one of two treatment sequences: the prototype mini lozenge followed by a commercially available mini lozenge, or the converse. After a 5 to 7 day washout period, subjects crossed over to receive the other study treatment. Blood sampling occurred pre- and post-dose nicotine and was assessed using a validated solid-phase extraction with ultra-high-performance liquid chromatography and tandem mass spectrometry. The primary endpoint was bioequivalence as determined by maximal plasma nicotine concentration (Cmax) and the extent of nicotine absorption (AUC0-t and AUC0-∞). The secondary endpoints included the time to Cmax (Tmax), half-life, the elimination constant (Kel), and safety. RESULTS: The prototype mini lozenge was bioequivalent to the commercially available mini lozenge, with no significant difference in Cmax, AUC0-t, or AUC0-∞ or any of the secondary outcomes. The most common treatment-emergent adverse event was throat irritation, of which all cases were mild in severity. There were no serious adverse events. CONCLUSION: The prototype mini lozenge is bioequivalent to a commercially available mini lozenge and may provide smokers with a new oral NRT option to aid in smoking cessation and of tobacco dependence through the relief of nicotine withdrawal symptoms, including cravings.
INTRODUCTION: Cigarette smoking remains a substantial public health problem. Nicotine replacement therapy (NRT) is an effective treatment that increases the success of a quit attempt. There are different NRT formats with no difference in efficacy, but their pharmaceutical form or route of administration may translate into individual preferences. A novel prototype mini lozenge was developed to offer smokers a new NRT option to aid in their quit attempt. Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge. METHODS: Two randomized, open-label, crossover studies were conducted to evaluate either the 2 or 4 mg dose level. Heavy smokers in otherwise good health were randomly assigned to one of two treatment sequences: the prototype mini lozenge followed by a commercially available mini lozenge, or the converse. After a 5 to 7 day washout period, subjects crossed over to receive the other study treatment. Blood sampling occurred pre- and post-dose nicotine and was assessed using a validated solid-phase extraction with ultra-high-performance liquid chromatography and tandem mass spectrometry. The primary endpoint was bioequivalence as determined by maximal plasma nicotine concentration (Cmax) and the extent of nicotine absorption (AUC0-t and AUC0-∞). The secondary endpoints included the time to Cmax (Tmax), half-life, the elimination constant (Kel), and safety. RESULTS: The prototype mini lozenge was bioequivalent to the commercially available mini lozenge, with no significant difference in Cmax, AUC0-t, or AUC0-∞ or any of the secondary outcomes. The most common treatment-emergent adverse event was throat irritation, of which all cases were mild in severity. There were no serious adverse events. CONCLUSION: The prototype mini lozenge is bioequivalent to a commercially available mini lozenge and may provide smokers with a new oral NRT option to aid in smoking cessation and of tobacco dependence through the relief of nicotine withdrawal symptoms, including cravings.