Efficacy and Safety Study of Nicotine Mint Lozenge (2mg and 4mg) in Smoking Cessation

Study Overview
=================
Brief Summary
-----------------
A multi-center, randomized, double-blind, placebo-controlled, 4-arm clinical study to evaluate efficacy and safety of nicotine lozenge (2mg and 4mg) in smoking cessation in adult cigarette smokers who are motivated to quit smoking. Successful quitters or participants who smoke occasionally will be followed up after week 24 till 12 months.

Official Title
-----------------
A Multi-center, Randomized, Double-blind, Parallel, Placebo-controlled Clinical Study to Evaluate Efficacy and Safety of Nicotine Mint Lozenge (2mg and 4mg) in Smoking Cessation

Conditions
-----------------
Smoking

Intervention / Treatment
-----------------
* Drug: Nicotine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be 18 years of age or older; Participant is motivated in smoking cessation using nicotine mint lozenge; Participant has the habit of smoking regularly every day for at least 1 year; Participant is able to read and provide written informed consent. Exclusion Criteria: Participant uses other forms of tobacco other than cigarettes such as pipes, cigars, snuff, or smokeless tobacco within 30 days of entry into the study; Participant uses other nicotine delivery system such as nicotine gum, nicotine patch, nicotine inhaler, or nicotine nasal spray etc. within 30 days of study entry; Participant smoke any other substance within 30 days of study entry (such as cannabis, cocaine, heroin, ice drug, herbal cigarettes etc); The participant has a past history of alcohol or drug abuse; Participants use other smoking cessation aids (including bupropion, varenicline, traditional Chinese medicines such as herbals, acupuncture, consultation etc), within 30 days of study entry.; Participant is currently involved in another clinical trial or has used any investigational medication within 30 days of study entry; Any previous participation in this study; Participant is a member of the same household as another clinical subject. Subject is a relative of study site staff or member of the study staff; Participant is pregnant or breast-feeding, or has childbearing potential but refusing taking medical contraception measures (within first 24 weeks during study). (Note: All female subjects with childbearing potential must take urine pregnancy test before entry the study, only negative result subject is permitted to this study.); Participants who have heart and cerebral vascular disease not stable or controlled by medication or have an irregular heartbeat or have had a heart attack within the last 3 months; Participants with poorly controlled high blood pressure by medications, systolic BP greater than or equal to 140mmHg, diastolic BP greater than or equal to 90mmHg after administration; Participants having hyperthyroidism or current application of insulin for diabetes; Participants having myocardial infarction or cerebral vascular accidents recently (within the past 3 months); Participants who are unable to fulfill study requirements in relation to conforming to the visit schedule; Participants who are allergy to Aspartame or Phenylpyruvic acid (an edulcorant is widely used in foods and drinks)，or have diagnosed with Phenylketonuria; The other clinically significant pulmonary, gastrointestinal, liver, neurological, renal or haematological abnormalities.( unstable or worsening angina pectoris, Prinzmetal's angina, nerve or circulatory problems, rheumatoid arthritis, moderate and severe COPD); A medical history that, in the opinion of the investigator, might jeopardize the safety of the subject or the validity for the study results.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2mg nicotine lozenge<br>2 mg nicotine lozenge | Drug: Nicotine<br>* 2 mg or 4 mg nicotine lozenge<br>|
| Placebo Comparator: 2 mg placebo<br>2 mg placebo | Drug: Placebo<br>* placebo lozenge<br>|
| Experimental: 4 mg nicotine lozenge<br>4 mg nicotine lozenge | Drug: Nicotine<br>* 2 mg or 4 mg nicotine lozenge<br>|
| Placebo Comparator: 4 mg placebo<br>4 mg placebo | Drug: Placebo<br>* placebo lozenge<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Successful Smoking Cessation at Week 6 | Rate of Successful Smoking Cessation at Week 6 was measured by Carbon Monoxide (CO) breath levels. | From baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Continuous abstinence was verified by measurement of CO breath levels. | From baseline to Week 12 and Week 24 | 
| Rate of Long-term Successful Smoking Cessation at Week 24 | Rate of long-term successful smoking cessation at Week 24 was defined as the proportion of participants who achieved the primary end-point with no more than six cumulative days of smoking from Week 6 to Week 24. | From Week 6 to Week 24 | 
| Proportion of Participants With Seven Day Point Prevalence Abstinence | Seven day point prevalence abstinence was defined as complete abstinence from smoking for the 7 days up to and including the evaluation day. | Weekly assessment at Week 1, 2, 4, 6, 12 and Week 24 | 
| Mean Score of Relief of Craving/ Total Withdrawal Symptoms | The evaluation of withdrawal and craving symptoms was carried out every day with the Minnesota Nicotine Withdrawal scale (MNWS). The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated on a 5 grade scale with scores ranging from 0 (best score) to 4 (worst score) i.e. none (score=0), slight (score=1), mild (score=2), moderate (score=3), and severe (score=4). For each symptom at each week, the average score was calculated as the average of the daily scores during that week. The total score was calculated as the sum of the 9 symptoms. | Weekly assessment at Week 1, 2, 3, 4, 5 and Week 6 | 
| Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Mean daily dose of lozenges was calculated as number of lozenges taken at each visit divided by days since the last visit. | Weeks 1-2, 3-4, 5-6, 7-12 and 13-24 | 
| Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Change in body weight was analyzed at Weeks 6, 12, and 24. | Baseline, Week 6, 12 and Week 24 | 
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | All AEs and SAEs were reviewed and reported by investigator. AEs were graded on a 3-point scale as Mild, Moderate and Severe. | Weekly assessments from first treatment dose up to 15 days after last treatment dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
smoking cessation, nicotine lozenge, nicotine replacement therapy