Evaluation of Nicotine Resinate 1.5mg Lozenge on Craving Reduction in Moderate Smokers: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to assess the efficacy of a single dose of **Nicotine 1.5mg lozenge** compared to placebo in reducing craving in moderate smokers placed in a non-smoking situation. This evaluation is conducted prospectively from 30 minutes up to 3 minutes in a reverse chronological manner. The clinical relevance of this objective lies in its potential to provide evidence for the effectiveness of nicotine lozenges as a smoking cessation aid, which could support smokers in managing cravings and ultimately aid in smoking cessation.

Secondary objectives include:

• Assessing the efficacy of the lozenge compared to placebo on craving reduction at 45, 60, and 90 minutes.
• Evaluating the efficacy over one day on overall craving and affective withdrawal symptoms such as anxiety, anger, irritability, difficulty concentrating, restlessness, and depressed mood.
• Evaluating global subject satisfaction and assessing the safety of the Nicotine 1.5mg lozenges.

The clinical trial focuses on the **cessation of smoking** and involves a study population comprising both male and female participants. The age range of the participants is 18 years and older, with a body mass index (BMI) between 18.5 and 29.5 kg/m². Participants are moderate smokers, defined as those who smoke 11-20 cigarettes per day and have a Fagerström score of 5 to 6. The trial does not include a vulnerable population. Participants were selected based on their motivation for smoking cessation, which is greater than 7 on the Richmond test. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the requirement for female participants of childbearing potential to use an efficient contraceptive method. The trial population was selected to ensure a negative antigenic test to SARS-CoV-2 or its variants at screening and on Day 0, and for female participants, a negative serum β-HCG test at screening and a negative urine β-HCG test on Day 0 if the screening test was conducted more than 72 hours prior. The sponsor has not provided information regarding the total number of participants.

The clinical trial is designed to evaluate the effects of **nicotine resinate** in a 1.5 mg lozenge form on the craving in moderate smokers placed in non-smoking situations. This study is a **randomized, double-blind, placebo-controlled** trial with parallel groups. The trial aims to assess the efficacy of a single dose of the nicotine lozenge compared to a placebo in reducing craving from 30 minutes up to 3 minutes in a reverse chronological manner. The trial is expected to commence on April 6, 2024, and conclude by June 5, 2024, with an estimated duration of two months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as age, smoking habits, and motivation for smoking cessation. A negative antigenic test for SARS-CoV-2 or its variants is required at screening and on Day 0. The study includes follow-up visits to monitor the primary endpoint, which is the change in the Questionnaire of Smoking Urges (QSU)-brief Total score from baseline at 30 minutes and earlier times. Secondary endpoints include improvements in QSU-brief scores at 45, 60, and 90 minutes, as well as the area under the curve of QSU-brief score improvement over 30 minutes, and changes in the Minnesota Nicotine Withdrawal Scale (MNWS) score at the end of Day 1.

The expected length of participant involvement is one day, with the primary and secondary endpoints assessed within this period. Conditions that may lead to early termination from the study include the occurrence of treatment-emergent adverse events (TEAEs) or treatment-emergent serious adverse events (TESAEs), as well as any clinically significant abnormalities in physical examinations or vital signs measurements. The study is conducted in accordance with ICH/GCP guidelines and national/local regulations, ensuring the safety and well-being of participants throughout the trial.

The clinical trial involves the administration of **NICOPASS 1.5 mg SANS SUCRE MENTHE FRAICHEUR**, a lozenge containing **nicotine resinate** as the active substance. This pharmaceutical form is a sugar-free mint-flavored lozenge, sweetened with aspartame and acesulfame potassium. The lozenge is designed for **oromucosal** administration, allowing the active substance to be absorbed through the mucous membranes in the mouth. The maximum daily dose is 31.5 mg, with a total treatment period of one day. The lozenge is manufactured by Pierre Fabre Medicament and is classified under the ATC code N07BA01, indicating its use as a nicotine replacement therapy. The trial aims to evaluate the efficacy of a single 1.5 mg dose in reducing craving in moderate smokers placed in non-smoking situations.

The study also includes a **placebo** group, utilizing a product labeled as **V0018 Placebo**. This placebo is used as a comparator to the active treatment to assess the efficacy of the nicotine lozenge. The placebo does not contain any active substance and is intended to mimic the appearance and administration route of the active lozenge, ensuring the study remains double-blind. The placebo is administered in the same manner as the active treatment, maintaining consistency in the trial's methodology. Participant compliance with the dosing schedule is monitored throughout the study to ensure accurate and reliable results.

The efficacy of the clinical trial will be assessed by evaluating the reduction of craving in moderate smokers using a single dose of a 1.5 mg nicotine lozenge compared to a placebo. The primary endpoint for efficacy evaluation is the change in the Questionnaire of Smoking Urges (QSU)-brief Total score from baseline at 30 minutes and any earlier times. Secondary endpoints include the improvement in QSU-brief Total score from baseline, changes at 45, 60, and 90 minutes, and the area under the curve of QSU-brief Total score improvement from baseline over 30 minutes. Additional secondary endpoints involve the Visual Analogue Scale (VAS) for global evaluation of craving during the day, the number of lozenges used, and changes from baseline in the Minnesota Nicotine Withdrawal Scale (MNWS) score at the end of Day 1. The study will also monitor the incidence, severity, causality, and outcomes of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs), as well as any clinically significant abnormalities in physical examinations and vital signs measurements.