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A Study to Assess Changes in Cigarette Consumption During a Switch to Very Low Nicotine Cigarettes

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ClinicalTrials.gov Identifier: NCT03571724
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : July 2, 2018
Sponsor:
Collaborator:
Celerion
Information provided by (Responsible Party):
22nd Century Group, Inc.

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.

Condition or disease Intervention/treatment Phase
Tobacco Use Other: Non-Menthol Very Low Nicotine Cigarettes Other: Menthol Very Low Nicotine Cigarettes Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Longitudinal ambulatory switching study
Masking: None (Open Label)
Primary Purpose: Other
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
Estimated Study Start Date : June 28, 2018
Estimated Primary Completion Date : October 28, 2018
Estimated Study Completion Date : March 28, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Non-Menthol Very Low Nicotine Cigarettes
Subjects will be switched from their usual brand to smoke Very Low Nicotine king size cigarettes
Other: Non-Menthol Very Low Nicotine Cigarettes
King size non-menthol cigarettes containing 0.4mg nicotine /g tobacco

Experimental: Menthol Very Low Nicotine Cigarettes
Subjects will be switched from their usual brand to smoke Very Low Nicotine king size Menthol cigarettes
Other: Menthol Very Low Nicotine Cigarettes
King size menthol cigarettes containing 0.4mg nicotine /g tobacco




Primary Outcome Measures :
  1. Cigarettes per Day [ Time Frame: daily 1 week before switch, then daily for 6 weeks. ]
    Primary objective is to measure a change in cigarette consumption behavior before, during and after switching from usual brand to to VLN cigarettes. Subjects will record their cigarette consumption daily in an electronic diary.


Secondary Outcome Measures :
  1. Biomarkers of Exposure - Total 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanol (NNAL) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in NNAL (4-methylnitrosamino)-1-3-pyridyl)-1-butanone biomarker) before, during, and after switching to VLN cigarettes

  2. Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in NNN before, during, and after switching to VLN cigarettes

  3. Biomarkers of Exposure - S-phenylmercapturic acid (S-PMA) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in S-PMA (benzene biomarker) before, during, and after switching to VLN cigarettes

  4. Biomarkers of Exposure - 3-hydroxypropylmercapturic acid (3-HPMA) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in 3-HPMA (acrolein biomarker) before, during, and after switching to VLN cigarettes

  5. Biomarkers of Exposure - 1-hydroxy pyrene(1-OHP) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in 1-OHP before, during, and after switching to VLN cigarettes

  6. Biomarkers of Exposure - Total nicotine equivalents [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Total 24 hour urine will be collected to evaluate changes in total nicotine equivalents before, during, and after switching to VLN cigarettes

  7. Biomarkers of Exposure - Carboxyhemoglobin (COHb) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Blood will be drawn to evaluate COHb before, during, and after switching to VLN cigarettes

  8. Biomarkers of Exposure -Cotinine [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Blood will be drawn to evaluate cotinine levels before, during, and after switching to VLN cigarettes

  9. Nicotine pharmacokinetics - Maximum nicotine concentration (C-Max) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of C-max at weeks -1, 2 and 6.

  10. Nicotine pharmacokinetics - Peak nicotine time (T-Max) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of T-Max at weeks -1, 2 and 6.

  11. Nicotine pharmacokinetics - Area under Nicotine concentration curve (AUC) [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of AUC at weeks -1, 2 and 6.

  12. Smoking topography - Puff Duration [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Puff duration will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session.

  13. Smoking topography - Puff Volume [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Puff volume will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session.

  14. Smoking topography - Peak Puff Flow Rate [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Peak Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session.

  15. Smoking topography - Average Flow Rate [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Average Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session.

  16. Smoking topography - Inter-puff Interval [ Time Frame: -1 week, and at 2 and 6 weeks. ]
    Inter-puff interval will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session.

  17. Subjective effects -Fagerstrom Test for Cigarette Dependance (FTCD) [ Time Frame: -1 week, and at 2, 4, and 6 weeks. ]
    Subjects will answer a FTCD questionnaire

  18. Subjective effects -Brief Questionnaire of Smoking Urges (QSU-Brief) [ Time Frame: -1 week, and at 2, 4, and 6 weeks. ]
    Subjects will answer a QSU-Brief questionnaire

  19. Subjective effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWA-R) [ Time Frame: -1 week, and at 2, 4, and 6 weeks. ]
    Subjects will answer a MNWA-R questionnaire. The MNWA is considered as the briefest scale among the self-report measures of nicotine withdrawal symptoms currently available. The original MNWA was developed by Hughes and Hatsukami in 1986. It consisted of nine nicotine withdrawal symptoms including craving. The scale was modified to reflect changes made in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for nicotine withdrawal. The total score of the scale range from 0 to 36 depending on participant's rate for the symptoms as not present (0), slight (1), mild (2), moderate (3), and severe (4). A high total score implies high nicotine addiction.

  20. Subjective effects - Perceived Health Risks [ Time Frame: -1 week, and at 2, 4, and 6 weeks. ]
    Subjects will answer a Perceived health risks questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   26 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03571724


Contacts
Contact: Edward L Carmines, Ph.D. 8045029275 ed@carminesconsulting.com
Contact: Juan S Tamburrino, Ph.D. 2152857140 jtamburrino@xxiicentury.com

Locations
United States, Nebraska
Celerion Recruiting
Lincoln, Nebraska, United States, 68502
Contact: Philip Matthew, MD    402-476-2811    philip.matthew@celerion.com   
Principal Investigator: Philip Matthew, MD         
United States, North Carolina
High Point Clinical Trials Recruiting
High Point, North Carolina, United States, 27265
Contact: Melanie Fein, MD    336-841-0700 ext 2530    mfein@HighPointCTC.com   
Principal Investigator: Melanie Fein, MD         
Sponsors and Collaborators
22nd Century Group, Inc.
Celerion
Investigators
Principal Investigator: Philip L Matthew, MD Celerion
Principal Investigator: Melanie Fein High Point Clinical Trials
  Study Documents (Full-Text)

Documents provided by 22nd Century Group, Inc.:
Study Protocol  [PDF] May 9, 2018


Responsible Party: 22nd Century Group, Inc.
ClinicalTrials.gov Identifier: NCT03571724     History of Changes
Other Study ID Numbers: CA24914
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 22nd Century Group, Inc.:
Very Low Nicotine
Cigarette
VLN

Additional relevant MeSH terms:
Nicotine
Menthol
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipruritics
Dermatologic Agents