NCT06691386

Nicotine Pharmacokinetics and Subjective Effects of Oral Nicotine Products Relative to Smokeless Tobacco in Adult Users

A Randomized, Controlled, Partial-Blind, Crossover Study to Characterize the Nicotine Pharmacokinetics and Subjective Effects of Five Oral Nicotine Products Relative to Moist Smokeless Tobacco (MST) in Adult MST Users

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Altria Client Services LLC · Industry
• Sex: All
• Age: 22 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to obtain information on nicotine exposure following the use of five oral tobacco-derived nicotine (OTDN) products relative to subjects' own brand moist smokeless tobacco (OBMST) product in adult moist smokeless tobacco (MST) users, as well as to characterize subjective effects under controlled use conditions. Male and female adult MST users between the ages of 22 to 65 years were recruited. The total duration of participation for each subject was approximately 34 days including screening and a 6-day in-clinic study confinement period.

Detailed description

This was a partial and single-blind (oral TDN products and subject only), randomized, 6-way crossover design to evaluate plasma nicotine PK and subjective effects associated with the use of different nicotine levels (6, 9, and 12 mg) and different flavors of oral TDN products (Wintergreen, Mint and Tobacco) and subjects' OBMST product. Subjects had to be regular users of one of the following OBMST products in Natural, Wintergreen, or Mint flavor variants (and a single Straight variant), and could not have rejected any of the listed flavors they did not use at the time: COPENHAGEN Fine Cut, COPENHAGEN Long Cut, SKOAL Long Cut, or GRIZZLY Long Cut. Products used in the study were: Product A 6 mg oral TDN pouch in Wintergreen (Test) Product B 9 mg oral TDN pouch in Wintergreen (Test) Product C 12 mg oral TDN pouch in Wintergreen (Test) Product D 9 mg oral TDN pouch in Mint (Test) Product E 9 mg oral TDN pouch in Tobacco (Test) Product F Subject's OBMST (Reference) Initial Screening Visit Screening was performed within 28 days prior to Check-in (Day -1). Medical and tobacco use histories and demographic data were collected. Other screening procedures included a physical examination (including oral cavity and oropharynx), vital signs, electrocardiogram (ECG), body mass index (BMI), clinical laboratory tests (hematology, clinical chemistry, routine urinalysis), human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and coronavirus disease 2019 (COVID-19) viral \[antigen\] tests, urine/saliva drug, urine/breath alcohol, cotinine screen, and serum pregnancy and follicle-stimulating hormone (FSH) tests (for females as appropriate). Follow-up Screening and Product Trial Visit Follow-up Screening To ensure subjects met inclusion criteria, they took a pinch reflecting their typical quid size and used their OBMST for at least 45 minutes; cans were weighed before and after subjects selected their pinch size. Subjects were allowed to "top off" their pinch within the first minute, after which the total mass used was recorded; the brand of MST product used was collected. Tobacco cessation information was provided. Subjects who responded negatively (i.e., unwilling to use and/or could not tolerate their OBMST for at least 45 minutes) did not continue in the study. Product Trial: Following completion of screening procedures, eligible subjects participated in a product trial at home for at least 5 days and were provided a single 14-pouch can of each of the five oral TDN products to be used ad libitum prior to Day -1 to allow subjects to become accustomed to the products. Subjects who responded negatively (i.e., unwilling to use and/or could not tolerate any of the oral TDN products \[e.g., experience AEs during the use of the oral TDN product that prevented them from continuing to use the product as judged by the Investigator\]) to any of the study products during the Product Trial did not continue in the study. Check-in and Randomization Subjects who met all inclusion criteria and none of the exclusion criteria checked in to the clinic on Day -1 at a time determined by the clinic. Subjects received a COVID-19 viral \[antigen\] test. Female subjects received a pregnancy test as well. Subjects demonstrated that they were able/willing to use the 12 mg nicotine product (Product C) by using one pouch for at least 45 minutes. The 12 mg demonstrated use session had to be completed at least 4 hours prior to the start of the first ad libitum use session. Subjects were trained on the questionnaires for familiarization with the questions, scales, and computerized tablets prior to randomization by completing the questionnaires during a training session. Subjects were randomized to 1 of 6 product sequences on Day -1 prior to the afternoon ad libitum product use episode. A 6x6 Latin Square was used for randomization, with the following sequences: Sequence 1 = ABFCED, Sequence 2 = BCADFE, Sequence 3 = CDBEAF, Sequence 4 = DECFBA, Sequence 5 = EFDACB, and Sequence 6 = FAEBDC. Subjects were stratified based on age (Males only \[Low (\<45), High (≥46)\]) and sex. A total of 64 subjects (63 males, 1 female) were enrolled and 56 subjects (55 males, 1 female) were ultimately randomized to one of six study product sequences. Subjects were not allowed to use any tobacco/nicotine-containing product other than the assigned ones from the time of Check-in on Day -1 through the completion of last study procedure on Day 6. Ad Libitum Product Use (Afternoon Use Session) On each of Days -1 through 5, subjects participated each afternoon, starting at least 2 hours after the last PK blood draw, as applicable, but no later than 16 hours prior to the following morning's controlled product use, in an approximately 2-hour (± 10 minutes) ad libitum product use episode. Subjects were allowed to use up to 2 units (oral TDN pouch or OBMST quid) of the same product as the assigned product for the following morning's controlled product use episode per randomization. Controlled Product Use (Pharmacokinetic Use Session) On the morning of each study day (Days 1 - 6), subjects used the assigned product under controlled conditions: * Oral TDN product (Products A, B, C, D, and E): use one unit of oral TDN product by placing the product in the mouth at the location chosen by the subject for 45 minutes. * OBMST product (Product F): use one quid of the OBMST by placing the product in the mouth at the location chosen by the subject for 45 minutes. The quid mass for each subject was determined at Screening, and was weighed to ± 0.1 g. Used oral TDN products and expectorate from the OTDN controlled product use episodes were collected; the used MST quids were discarded. PK Blood Sample Collection On Days 1 through 6, venous blood samples (\~4 mL) for nicotine PK were collected at 5 minutes prior to, and at 5, 15, 30, 40, 45, 50, 60, 90, 120, and 180 minutes following the start of each controlled product use episode. Used study products were collected (with the exception of the OBMST) for analysis of residual nicotine. Subjective Effects Measures For collection of primary outcome measures subjects completed the following subjective measures questionnaires: * Smokeless Urge and Craving Questionnaire before, during, and following each controlled product use episode * Product Effects Questionnaire during and following each controlled product use episode Available data from all 56 randomized subjects (55 males, 1 female) were included in the analysis of primary outcome measures.

Conditions

• Tobacco Use

Interventions

Type	Name	Description
OTHER	Test Product A	Use of Test Product A in controlled use and ad libitum use sessions
OTHER	Test Product B	Use of Test Product B in controlled use and ad libitum use sessions
OTHER	Test Product C	Use of Test Product C in controlled use and ad libitum use sessions
OTHER	Test Product D	Use of Test Product D in controlled use and ad libitum use sessions
OTHER	Test Product E	Use of Test Product E in controlled use and ad libitum use sessions
OTHER	Reference Product F: Subjects' OBMST	Use of Reference Product F in controlled use and ad libitum use sessions. The subjects' Own Brand Moist Smokeless Tobacco (OBMST) reference products used in this study were commercially available and had been reported by the subjects as the brands they usually consume.

Timeline

• Start date: 2023-02-06
• Primary completion: 2023-05-10
• Completion: 2024-02-08
• First posted: 2024-11-15
• Last updated: 2025-01-17

Locations

2 sites across 1 country: United States