CSD190301: A Study to Assess Elements of Abuse Liability for Two Dissolvable Nicotine Lozenge Tobacco Products

Study Overview
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Brief Summary
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This is a two-arm, single use, single-center, randomized, 10-sequence per arm, open-label, crossover pharmacokinetic/pharmacodynamic (PK/PD) study, designed to evaluate elements of abuse liability (AL) including subjective effects, plasma nicotine uptake, and physiological measures during and following ad libitum use of the study investigational products (IPs) by generally healthy subjects.

Detailed Description
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Cigarette smokers and smokers who also use smokeless tobacco (SST) [e.g., snus, moist snuff] will be recruited into the study. Starting on Day -1, eligible subjects will be confined at the clinical site for 6 days. Subjects will be randomized to evaluate one IP in each of five separate Test Sessions, such that each subject will evaluate five IPs: one of two forms of the nicotine lozenge in three different regimens, a commercially-available nicotine replacement therapy (NRT) nicotine lozenge, and the subjects' usual brand (UB) cigarettes. Each Test Session will last for approximately 6 hours during and following IP use and will include collection of subjective measures, PK assessments and physiological measures. On Day -1, subjects will be instructed on how to use both the specific lozenge IP in their assigned study arm and the NRT lozenge and will have one trial use of both IP.

Official Title
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CSD190301: A Study to Assess Elements of Abuse Liability for Two Dissolvable Nicotine Lozenge Tobacco Products During a 6-Day In-Clinic Confinement

Conditions
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Smoking, Tobacco Use, Tobacco Smoking

Intervention / Treatment
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* Other: Product A
* Other: Product B
* Other: Product C
* Other: Product D
* Other: Product E
* Other: Product F
* Other: Product G
* Other: Product H


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English. Generally healthy male or female, 21 to 60 years of age, inclusive, at the time of consent. Expired breath carbon monoxide level is ≥ 10 ppm and ≤ 100 ppm at Screening. Positive urine cotinine test at Screening. Smokes combustible, filtered, non-menthol or menthol cigarettes, 83 mm to 100 mm in length as primary source of tobacco. Other cigarette sizes may be allowed with sponsor approval. Smokers who also use smokeless tobacco products may be enrolled. Agrees to smoke same UB cigarette throughout the study period. UB cigarette is defined as the reported cigarette brand style currently smoked most frequently by the subject. Smokes at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening. Response at Screening to Fagerström Test for Nicotine Dependence (FTND) Question 1 (How soon after you wake up do you smoke your first cigarette?) is either Within 5 minutes or 6-30 minutes. Willing to use UB cigarette, nicotine lozenges, and Nicorette® lozenge during the study period. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each Test Session. Females must be willing to use a form of contraception acceptable to the Principal Investigator (PI) from the time of signing informed consent until End-of-Study. Agrees to in-clinic confinement of 6 days (5 nights). Exclusion Criteria: Uses vapor products (e.g., e-cigarettes, tank systems) more than one day per week, for the past 6 months prior to screening. Presence of clinically significant uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, psychiatric, hematological, neurological disease, or any other concurrent disease or medical condition that, in the opinion of the PI, makes the study subject unsuitable to participate in this clinical study. History, presence of, or clinical laboratory test results indicating diabetes. Known history of sensitivity to aspartame / phenylalanine Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg, measured after being seated for five minutes at screening and at Day -1. Weight of ≤ 110 pounds. Hemoglobin level is < 12.5 g/dL for females or <13.0 g/dL for males at Screening. Scheduled treatment for asthma currently or within the past consecutive 12 months prior to the Screening Visit. As-needed treatment, such as inhalers, may be included at the PI's discretion pending approval from the Medical Monitor. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed. Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), or lobelia extract within (≤) 30 days prior to the signing of informed consent. History or presence of bleeding or clotting disorders. Any use of anticoagulants or aspirin (≥ 325 mg/day). Whole blood donation within 8 weeks (≤ 56 days) prior to the signing of informed consent. Plasma donation within (≤) 7 days prior to the signing of informed consent. Participation in another clinical trial within (≤) 30 days prior to the signing of informed consent. The 30-day window for each subject will be derived from the date of the last study event in the previous study to the time of signing the informed consent form (ICF) in the current study. Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study. Individuals ≥ 35 years of age currently using systemic, estrogen-containing contraception or hormone replacement therapy. A positive urine drug screen without evidence of prescribed corresponding concomitant medication(s) at Screening or Day -1. Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or a previous attempt within (≤) 30 days prior to signing the ICF. Drinks more than 21 servings of alcoholic beverages per week or has a positive alcohol breathalyzer result at Screening or Day -1. Employed by a tobacco or nicotine company, the study site, or handles tobacco- or nicotine-containing products as part of their job. Determined by the PI to be inappropriate for this study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hard nicotine lozenge arm<br>Subjects will use each of the 5 products sequentially during an evaluation period, followed by a 6 hour Test Session. | Other: Product A<br>* Usual brand (UB) filtered, combustible cigarette<br>Other: Product B<br>* Nicorette® Mint 4 mg nicotine lozenge<br>Other: Product C<br>* CSD1903-11, a hard nicotine lozenge, 2 mg nicotine<br>Other: Product D<br>* CSD1903-11, a hard nicotine lozenge, 4 mg nicotine<br>Other: Product E<br>* CSD1903-11, a hard nicotine lozenge, 8 mg nicotine<br>|
| Experimental: Soft nicotine lozenge arm<br>Subjects will use each of the 5 products sequentially during an evaluation period, followed by a 6 hour Test Session. | Other: Product A<br>* Usual brand (UB) filtered, combustible cigarette<br>Other: Product B<br>* Nicorette® Mint 4 mg nicotine lozenge<br>Other: Product F<br>* CSD1903-12, a soft nicotine lozenge, 2 mg nicotine<br>Other: Product G<br>* CSD1903-12, a soft nicotine lozenge, 4 mg nicotine<br>Other: Product H<br>* CSD1903-12, a soft nicotine lozenge, 8 mg nicotine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUEC PL 5-360 | area under the effects curve (AUEC) for product liking (PL) Visual Analogue Scale (VAS) score-versus-time curve from 5 minutes to 360 minutes after the start of IP use. Data is collected from a 100 point VAS scale; Range from 0 = Strongly dislike to 100 = Strongly Like | 5, 7.5, 10, 15, 20, 30, 45, 60, 120, 180, 240, and 360 minutes | 
| Emax PL | maximum product liking Visual Analogue Scale (VAS) score after the start of IP use. Data is collected from a 100 point VAS scale; Range from 0 = Strongly dislike to 100 = Strongly Like | 360 Minutes |