Evaluation of the Abuse Liability of Very Low Nicotine (VLN) Cigarettes

Conditions:Smoking Cessation
Therapuetic Areas:Pulmonary / Respiratory Diseases
Age Range:22 - 65
Start Date:April 13, 2018
End Date:July 26, 2018
Contact:Debra Kelsh, MD

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Evaluation of the Abuse Liability of Very Low Nicotine (VLN) Cigarettes With Characterization of Nicotine Exposure Profiles in Adult Smokers

This study is designed to evaluate the abuse liability of very low nicotine cigarettes
compared to nicotine gum and usual brand cigarettes

This study will be a randomized, two-part, 3-way crossover designed to evaluate the abuse
liability, pharmacokinetics (PK), and product use behavior associated with study products,
including VLN cigarettes, subjects' own-brand cigarettes, and nicotine polacrilex gum in
healthy adult male and female exclusive smokers. Subjects will participate in a standard
Screening visit and one 7-day Confined Assessment Phase, which will include a product trial
session (Day -1), and two study parts (Part A and Part B). Following the Screening visit,
eligible subjects will check-in to the study site on Day -1. Following the polacrilex gum
training session, subjects will be required to abstain from nicotine- and tobacco-containing
products for approximately 20 hours until the first product use session on Days 1 to 3; use
of other nicotine-containing products will be prohibited throughout the study. No additional
tobacco or nicotine products will be provided after the second product use on Days 4 to 6.

On Day 1, subjects will be randomized to one of three product sequence groups in Part A,
which will consist of an ad libitum product use session for each of the following study
products for 4 hours in a randomized crossover manner (Days 1 to 3; one product per day):

Product A: VLN cigarette

Product B: Own-brand filtered standard king size cigarette

Product C: 4 mg Nicotine polacrilex gum

A pharmacodynamic measure ("use product again" Visual Analog Scale (VAS)) will be
administered at the end of each ad libitum product use period. Product use behaviors (i.e.,
number of units consumed,duration of gum in mouth) will be collected throughout each ad
libitum product use period. Upon completion of Part A, subjects will be randomized to one of
three product sequence groups in Part B, which will consist of 3 study days (Days 4 to 6),
with one product per day. Each study day will consist of: 1) Controlled Product Use Session
(10 puffs from their own-brand cigarette or VLN cigarette [maximum 3 ± 2 seconds per puff] at
approximately 30 ± 5-second interpuff intervals, or chew the nicotine polacrilex gum using
the "chew and park" method for 10 minutes); and 2) Uncontrolled Product Use Session (ad
libitum use for 10 minutes). The Controlled Product Use Session and Uncontrolled Product Use
Session will be separated by approximately 6 hours. During Part B, pharmacodynamic measures,
PK, and product use behavior (Uncontrolled only) will be collected at various time points
each day.

Inclusion Criteria:

Subjects will be required to meet each one of the following inclusion criteria in order to
be eligible for participation in the study:

1. Must provide written informed consent prior to the initiation of any protocol-specific

2. Male and female adults, between 22 to 65 years of age, inclusive.

3. Body mass index (BMI) within 18.0 to 35.0 kg/m2, inclusive (minimum weight of at least
50.0 kg at Screening).

4. Healthy, as determined by no clinically significant medical history, physical
examination, 12-lead ECG, vital signs or laboratory (including hematology, clinical
chemistry, urinalysis, and serology) findings at Screening, as judged by an

5. Smoking history of an average of at least 10 manufactured filtered standard (i.e., not
slim) king size combustible cigarettes daily for at least 1 year prior to Screening.
Brief periods (i.e., up to 7 consecutive days) of non-smoking during the 3 months
prior to Screening (e.g., due to illness or participation in a study where smoking was
prohibited) will be permitted.

6. Self-reporting of desire to smoke within approximately 30 minutes of waking.

7. Positive urine cotinine (≥500 ng/mL) at Screening.

8. Negative pregnancy test at Screening and Day -1 (check-in) for all female subjects.

9. Female subjects of non-childbearing potential must be surgically sterile or 1 year
postmenopausal (as confirmed by serum Follicle Stimulating Hormone (FSH) > 35 U/L). A
subject is considered to be surgically sterile if she has had a tubal ligation,
hysterectomy, bilateral salpingo-oophorectomy or bilateral oophorectomy, or
hysterectomy with bilateral salpingo-oophorectomy. If the subject is of childbearing
potential, she must be using a medically accepted method of contraception and agree to
continued use of this method for the duration of the study and for 30 days after
completion of the study. Acceptable methods of contraception include abstinence, birth
control pill, or an intrauterine device (known to have a failure rate of less than 1%
per year) or double barrier method of contraception (e.g., male condom in addition to
a diaphragm, contraceptive sponge or spermicide).

10. Able to speak, read, and understand English sufficiently to allow completion of all
study assessments.

11. Must be willing to comply with the requirements and restrictions of the study.

Exclusion Criteria:

Subjects will not be eligible to participate in this study if any one of the following
exclusion criteria is met:

1. Inability to tolerate 4 mg nicotine polacrilex gum during product use trial on Day -1
(check-in) or dentition prevents subjects from chewing gum.

2. History or presence of any clinically significant cardiac, psychiatric, endocrine,
hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic,
dermatologic, renal, or other major disease at Screening, which in the opinion of an
investigator would jeopardize the safety of the subject or the validity of the study

3. History or presence of any type of malignant tumors.

4. Clinically significant abnormal findings on the vital signs, physical examination
(including oral exam), medical history, or clinical laboratory results, in the opinion
of an investigator.

5. Positive serology test results for human immunodeficiency virus (HIV-1/HIV-2)
Antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C Antibody (HCVAb).

6. An acute illness (e.g., upper respiratory infection, viral infection) requiring
treatment within 2 weeks prior to Day -1 (check-in).

7. Drug or alcohol abuse or dependence within the 24 months prior to Screening (except
nicotine), as defined by the Diagnostic and Statistical Manual of Mental Disorders,
4th edition text revision (DSM-IV-TR), or any self-reported dependence or "addiction"
within the subject's lifetime (except nicotine or caffeine).

8. Subjects who have ever been in treatment for substance use disorder(s) or who are

9. Positive urine drug screen (UDS) or urine alcohol test at Screening or Day -1

10. History or any current conditions that may interfere with drug absorption,
distribution, metabolism, or excretion.

11. History of severe allergic reaction (including anaphylaxis) to any substance, or
previous status asthmaticus, or food allergies/intolerances/restrictions, or special
dietary needs which, in the judgment of an investigator, contraindicates the subject's
participation in the study.

12. Requires concomitant treatment with prescription or non-prescription products that
contain pseudoephedrine (e.g., nasal/sinus decongestants).

13. Self-reported use of nicotine polacrilex gum, or other nicotine replacement therapy
products in the 30 days prior to Day -1 (check-in). Isolated incidents within 30 days
prior to Day -1 (check-in) may be permitted at the discretion of the investigator.

14. Subject has unsuitable or difficult venous access or is unwilling or unable to undergo
direct venipuncture or catheter insertion.

15. Subject has donated or lost 100 to 499 mL whole blood within 30 days or more than 499
mL whole blood within 56 days preceding entry into the Confined Assessment Phase.

16. Subject is an employee of the sponsor or research site personnel directly affiliated
with this study or their immediate family member defined as a spouse, parent, child or
sibling, whether biological or legally adopted.

17. Subject is lactating and or breast feeding.

18. A subject who, in the opinion of an investigator, is considered unsuitable or unlikely
to comply with the study protocol for any reason.
We found this trial at
Overland Park, Kansas 23112
Principal Investigator: Debra Kelsh, MD
Phone: 913-696-1601
Overland Park, KS
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