A Longitudinal Ambulatory Study to Assess Changes in Cigarette Consumption and Biomarkers of Exposure During a 6-week Switch to Very Low Nicotine Cigarettes

22nd Century Group, Inc.2 sites in 1 country142 target enrollmentJune 28, 2018

ConditionsTobacco Use

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Tobacco Use
Sponsor: 22nd Century Group, Inc.
Enrollment: 142
Locations: 2
Primary Endpoint: Cigarettes Per Day
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 28, 2018

End Date

March 8, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

22nd Century Group, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Potential subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study.
•Is a healthy adult male or female adult smoker, 26 to 65 years of age, inclusive, at Screening.
•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.
•Reports smoking an average of 10 or more manufactured combustible cigarettes per day at Screening.
•Usual brand (UB) of cigarette is a filtered king size cigarette (with an approximate length of 84 mm (± 3 mm)).
•Has a positive urine cotinine (≥ 500 ng/ml) at Screening.
•Has an exhaled Carbon Monoxide \> 10 ppm at Screening.
•If female, has a negative serum pregnancy test at Screening.
•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;

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.
•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.
•Clinically significant abnormal findings on the physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Investigator.
•Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
•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.
•Fever (\>100.5 degrees F) at Screening or first clinic visit.
•Body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.
•History of drug or alcohol abuse or has used medical/recreational marijuana within 12 months of Screening.
•Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator.
•Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening, unless deemed not clinically significant by the PI.

Outcomes

Primary Outcomes

Cigarettes Per Day

Time Frame: Assessed daily from Week -1 to Week 6; Week -1, Week 2, and Week 6 reported

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. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).All 142 randomized subjects were included in the ITT population based on product use. Out of these, 71 subjects were included in the PP Population and 71 were excluded. All excluded subjects had a ratio of \[plasma cotinine/CPD VLN\]/\[plasma cotinine/CPD baseline\] \> 0.2. It was pre-specified to exclude participants with a ratio \>0.2 as they were considered non-compliant.

Secondary Outcomes

Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN)(-1 week, and at 2 and 6 weeks.)
Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA)(-1 week, and at 2 and 6 weeks.)
Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA)(-1 week, and at 2 and 6 weeks.)
Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max)(Week -1, and at 2 and 6 weeks.)
Smoking Topography - Puff Duration(-1 week, and at 2 and 6 weeks.)
Smoking Topography - Puff Volume(-1 week, and at 2 and 6 weeks.)
Smoking Topography - Inter-puff Interval(-1 week, and at 2 and 6 weeks.)
Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD)(-1 week, and at 2, 4, and 6 weeks.)
Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL)(-1 week, and at 2 and 6 weeks.)
Biomarkers of Exposure - Total Nicotine Equivalents(-1 week, and at 2 and 6 weeks.)
Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max)(Week -1, and at 2 and 6 weeks.)
Smoking Topography - Peak Puff Flow Rate(-1 week, and at 2 and 6 weeks.)
Biomarkers of Exposure - Carboxyhemoglobin (COHb)(Week -1, and at 2 and 6 weeks.)
Biomarkers of Exposure -Cotinine(Week -1, and at 2 and 6 weeks.)
Smoking Topography - Average Flow Rate(-1 week, and at 2 and 6 weeks.)
Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R)(-1 week, and at 2, 4, and 6 weeks.)
Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP)(-1 week, and at 2 and 6 weeks.)
Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC)(Week -1, and at 2 and 6 weeks.)
Subjective Effects - Perceived Health Risks(-1 week, and at 2, 4, and 6 weeks.)
Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief)(Week -1, and at 2, 4, and 6 weeks.)