Clinical trial NCT03571724: A Study to Assess Changes in Cigarette Consumption During a Switch to Very Low Nicotine Cigarettes
Official title: A Longitudinal Ambulatory Study to Assess Changes in Cigarette Consumption and Biomarkers of Exposure During a 6-week Switch to Very Low Nicotine Cigarettes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Use
Keywords: Very Low Nicotine
Cigarette
VLN
Lead sponsor: 22nd Century Group, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2018-06-28
Enrollment: 142
Sex: ALL
Minimum age (years): 26
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Longitudinal ambulatory switching study
Primary purpose: OTHER

Brief summary: This study evaluates the impact of switching from usual brand cigarettes to very low nicotine cigarettes on cigarette consumption, smoking behavior, and biomarkers of exposure.

Detailed description: Very low nicotine (VLN) cigarettes contain a 'non-additive' level of nicotine. This study will switch smokers from their usual brand to VLN cigarettes. Periodically during the study the investigators will collect blood and measure nicotine exposure and also other biomarkers to see what effect switching has. The participants will also use a diary to record number of cigarettes smoked. Cigarette butts will also be collected.

Eligibility criteria: Inclusion Criteria:

Potential subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study.

1. Is a healthy adult male or female adult smoker, 26 to 65 years of age, inclusive, at Screening.
2. Has been a smoker for at least 5 years prior to Screening. Brief periods of non smoking (e.g., up to 7 consecutive days due to illness, trying to quit, participation in a study where smoking was prohibited) during that time will be permitted at the discretion of the Investigator.
3. Reports smoking an average of 10 or more manufactured combustible cigarettes per day at Screening.
4. Usual brand (UB) of cigarette is a filtered king size cigarette (with an approximate length of 84 mm (± 3 mm)).
5. Has a positive urine cotinine (≥ 500 ng/ml) at Screening.
6. Has an exhaled Carbon Monoxide \> 10 ppm at Screening.
7. If female, has a negative serum pregnancy test at Screening.
8. A female subject of childbearing potential must have been using one of the following forms of contraception and agree to continue using it through completion of the study:

   * hormonal (e.g., oral, vaginal ring, transdermal patch, implant, or injection) consistently for at least 3 months prior to Screening;
   * double barrier method (e.g., condom with spermicide, diaphragm with spermicide) consistently for at least 14 days prior to Screening;
   * intrauterine device for at least 3 months prior to Screening;
   * Essure® or similar nonsurgical sterilization procedure at least 6 months prior to Screening
   * a partner who has been vasectomized for at least 6 months prior to Screening;
   * abstinence beginning at least 14 days prior to Screening and through the End of Study.
9. A female subject of non childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Screening:

   * hysteroscopic sterilization;
   * bilateral tubal ligation or bilateral salpingectomy;
   * hysterectomy;
   * bilateral oophorectomy; Or be postmenopausal with amenorrhea for at least 1 year prior to Day 1 and follicle stimulating hormone (FSH) levels consistent with postmenopausal status.
10. Willing to comply with the requirements of the study, including a willingness to use the test products.
11. Voluntary consent to participate in this study documented on the signed informed consent form (ICF).
12. Subject is not planning to leave the area during the course of the study.

Exclusion Criteria:

Subjects may be excluded from the study if there is evidence of any of the following criteria at Screening, start of Week -1 (first clinic visit), or during the study as noted, in the opinion of the Investigator.

1. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary (especially bronchospastic diseases and asthma), immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2. Clinically significant abnormal findings on the physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Investigator.
3. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
4. An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment with prescription medication(s) within 14 days prior to Screening or first clinic visit.
5. Fever (\>100.5 degrees F) at Screening or first clinic visit.
6. Body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.
7. History of drug or alcohol abuse or has used medical/recreational marijuana within 12 months of Screening.
8. Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator.
9. Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening, unless deemed not clinically significant by the PI.
10. Seated systolic blood pressure \<90 mmHg or \>150 mmHg, diastolic blood pressure \<40 mmHg or \>95 mmHg at Screening, unless deemed not clinically significant by the PI.
11. Positive urine screen for drugs of abuse or alcohol at Screening or at the first clinic visit.
12. Female subjects who are pregnant, lactating, or intend to become pregnant from Screening through the End of Study.
13. Use of medications known to interact with cytochrome p450 2A6 (including, but not limited to, amiodarone, desipramine, isoniazid, ketoconazole, miconazole, phenobarbital, rifampin, tranylcypromine, methoxsalen) within 3 months prior to Screening and throughout the study.
14. Use of inhalers to treat any medical condition within 3 months prior to Screening and throughout the study.
15. Use of nicotine-containing products other than factory manufactured cigarettes \[e.g., roll-your-own cigarettes, e-vapor products, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum\] within 28 days prior to Screening.
16. Use of any prescription smoking cessation treatments, including, but not limited to, varenicline (Chantix®) or buproprion (Zyban®) within 3 months prior to Screening.
17. Self-reported puffer/non-inhaler (i.e., a smoker who draws smoke from the cigarette into the mouth and throat but does not inhale).
18. Planning to quit smoking during the study period or postponing a quit attempt in order to participate in the study.
19. Plasma donation within 7 days prior to Screening or at any time during the study.
20. Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Screening.
21. Participation in a previous clinical study for an investigational drug, device, biologic, or tobacco product within 30 days prior to Screening.
22. Subject or a first-degree relative (i.e., parent, sibling, child) is a current or former employee of the tobacco industry or a named party or class representative in litigation with the tobacco industry.
23. Subject or a first-degree relative (i.e., parent, sibling, child) is a current employee of the clinic sites.

Primary outcomes:
measure: Cigarettes Per Day
timeFrame: Assessed daily from Week -1 to Week 6; Week -1, Week 2, and Week 6 reported
Secondary outcomes:
measure: Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL)
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN)
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA)
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA)
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP)
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - Total Nicotine Equivalents
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Biomarkers of Exposure - Carboxyhemoglobin (COHb)
timeFrame: Week -1, and at 2 and 6 weeks.
measure: Biomarkers of Exposure -Cotinine
timeFrame: Week -1, and at 2 and 6 weeks.
measure: Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max)
timeFrame: Week -1, and at 2 and 6 weeks.
measure: Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max)
timeFrame: Week -1, and at 2 and 6 weeks.
measure: Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC)
timeFrame: Week -1, and at 2 and 6 weeks.
measure: Smoking Topography - Puff Duration
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Smoking Topography - Puff Volume
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Smoking Topography - Peak Puff Flow Rate
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Smoking Topography - Average Flow Rate
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Smoking Topography - Inter-puff Interval
timeFrame: -1 week, and at 2 and 6 weeks.
measure: Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD)
timeFrame: -1 week, and at 2, 4, and 6 weeks.
measure: Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief)
timeFrame: Week -1, and at 2, 4, and 6 weeks.
measure: Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R)
timeFrame: -1 week, and at 2, 4, and 6 weeks.
measure: Subjective Effects - Perceived Health Risks
timeFrame: -1 week, and at 2, 4, and 6 weeks.
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
city: High Point
country: United States
facility: High Point Clinical Trials
state: North Carolina
Study officials:
affiliation: Celerion
name: Philip L Matthew, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: High Point Clinical Trials
name: Melanie Fein
role: PRINCIPAL_INVESTIGATOR
References: