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

NCT06691386 | Completed

• 1 other identifier: ALCS-REG-22-03-OTDN
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Tobacco Use

Keywords

Tobacco; Moist Tobacco; Oral Derived Tobacco Nicotine

Outcome Measures

Primary Outcomes (3)

• Plasma Nicotine (ng/mL)

  Maximum plasma nicotine concentration (Cmax) measured following the product use under controlled use conditions

  Day 1 through Day 6

• Smokeless Urge and Craving Questionnaire

  Maximum reduction in response relative to pre-use for subjective ratings of all items in the Smokeless Urge and Craving Questionnaire (Emax-UC) following the product use under controlled use conditions. Each question was paired with a 100 millimeter (mm) visual analog scale (VAS). The VAS was anchored with "Not at All" on the left and "Extremely on the right. Subjects placed a vertical line at a place along the VAS based on how he/she felt in the moment. Scoring of response based on measurement of distance in mm from "Not at All" hash to mark made by subject with no response being better or worse.

  Day 1 through Day 6

• Product Effects Questionnaire

  Maximum response for subjective ratings of all items in the Product Effects Questionnaire (Emax-PE) following the product use under controlled use conditions. Each question was paired with a 100 millimeter (mm) visual analog scale (VAS). The VAS was anchored with "Not at All" on the left and "Extremely" on the right. Subjects placed a vertical line at a place along the VAS based on how he/she felt in the moment. Scoring of response based on measurement of distance in mm from "Not at All" hash to mark made by subject with no response being better or worse.

  Day 1 through Day 6

Study Arms (6)

Randomization Sequence 1 = ABFCED

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Test Product A Test Product B Reference Product F Test Product C Test Product E Test Product D

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Randomization Sequence 2 = BCADFE

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Test Product B Test Product C Test Product A Test Product D Reference Product F Test Product E

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Sequence 3 = CDBEAF

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Test Product C Test Product D Test Product B Test Product E Test Product A Reference Product F

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Sequence 4 = DECFBA

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Test Product D Test Product E Test Product C Reference Product F Test Product B Test Product A

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Sequence 5 = EFDACB

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Test Product E Reference Product F Test Product D Test Product A Test Product C Test Product B

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Sequence 6 = FAEBDC

EXPERIMENTAL

Usage of Test and Reference study products in controlled use and ad libitum use sessions during the 6 day in-clinic period in following order: Reference Product F Test Product A Test Product E Test Product B Test Product D Test Product C

Other: Test Product A; Other: Test Product B; Other: Test Product C; Other: Test Product D; Other: Test Product E; Other: Reference Product F: Subjects' OBMST

Interventions

Test Product A OTHER

Use of Test Product A in controlled use and ad libitum use sessions

Also known as: Prototype 6 mg nicotine oral TDN pouch in Wintergreen flavor

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Test Product B OTHER

Use of Test Product B in controlled use and ad libitum use sessions

Also known as: Prototype 9 mg nicotine oral TDN pouch in Wintergreen flavor

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Test Product C OTHER

Use of Test Product C in controlled use and ad libitum use sessions

Also known as: Prototype 12 mg nicotine oral TDN pouch in Wintergreen flavor

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Test Product D OTHER

Use of Test Product D in controlled use and ad libitum use sessions

Also known as: Prototype 9 mg nicotine oral TDN pouch in Mint flavor

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Test Product E OTHER

Use of Test Product E in controlled use and ad libitum use sessions

Also known as: Prototype 9 mg nicotine oral TDN pouch in Tobacco flavor

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Reference Product F: Subjects' OBMST OTHER

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.

Also known as: COPENHAGEN SNUFF Fine Cut, COPENHAGEN Long Cut Mint, COPENHAGEN Long Cut, COPENHAGEN Long Cut Wintergreen, SKOAL Long Cut Mint, SKOAL Long Cut Straight, SKOAL Long Cut Wintergreen, GRIZZLY Long Cut Mint, GRIZZLY Long Cut Natural, GRIZZLY Long Cut Wintergreen

Randomization Sequence 1 = ABFCED; Randomization Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC

Eligibility Criteria

• Age: 22 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary consent to participate in this study documented on the signed informed consent form (ICF).
• Adult males and females 22 to 65 years of age, inclusive, at Screening. Full COVID-19 vaccination (FDA authorized vaccines) record that was completed at least 14 days prior to Screening for subjects \>45 years of age. Full vaccination as defined by the Centers for Disease Control and Prevention.
• Positive urine cotinine (≥ 500 ng/mL) at Screening.
• Negative pregnancy test at Screening, prior to the start of Product Trial, and Check-in (Day -1) for all female subjects.
• Female subjects who are heterosexually active and of childbearing potential (e.g., not surgically sterile at least 6 months prior to Check-in nor postmenopausal with amenorrhea for at least 1 year prior to Check-in and FSH levels consistent with postmenopausal status) 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, injection) consistently for at least 3 months prior to Check-in,
• double barrier (e.g., condom with spermicide or diaphragm with spermicide) consistently for at least 2 weeks prior to Check-in,
• intrauterine device for at least 3 months prior to Check-in,
• exclusive partner who has been vasectomized for at least 6 months (inclusive) prior to Check-in.
• Female subjects of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.
• Female subjects who are of nonchildbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Check-in:
• hysteroscopic sterilization with documentation of success with hysterosalpingogram;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to Check-in and have FSH levels consistent with postmenopausal status.

You may not qualify if:

• Subjects will be excluded from the study if there is evidence of any of the following criteria at Screening or Check-in, or at any time during the study as appropriate.
• An ad libitum pinch mass that is less than 2 g as captured at the Follow-up Screening visit.
• Use of any oral TDN or nicotine-containing products with the exception of MST and combustible cigarettes (e.g., nicotine lozenge, nicotine gum, nicotine inhaler, nicotine mouth spray, nicotine pouch) within the past 30 days prior to the screening visit.
• Any postponement of a quit attempt in order to participate in the study.
• Attempts to quit MST product use in the 3 months prior to Day -1 (Check- in).
• Planning to quit MST product use in the next 3 months (from Screening visit).
• Negative response (i.e., unwilling to use or unable to tolerate \[e.g., experiences AEs during the Product Trial that will prevent them from continuing to use the product as judged by the Investigator\]) to any of the oral TDN study products during the Product Trial.
• Dentition that prevents subjects from using products.
• History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, 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 vital signs, physical examination (including oral cavity and oropharynx), medical history, or clinical laboratory results, in the opinion of the Investigator.
• Positive test for HIV, HBsAg, COVID-19 or HCV at Screening or Check-in, as applicable.
• History or presence of any type of malignant tumors.
• Current evidence or any history of congestive heart failure.
• An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to Check-in or at the discretion of the Investigator.
• Presence of gum bleeding and/or abscess, open mouth sores or oral ulcers at Screening or Check-in.

Sponsors & Collaborators

• Altria Client Services LLC: lead
• Celerion: collaborator

Study Sites (2)

Pillar Clinical Research LLC

Bentonville, Arkansas, 72712, United States

Location

QPS Bio-Kinetic

Springfield, Missouri, 65802, United States

Location

MeSH Terms

Conditions

Tobacco Use

Condition Hierarchy (Ancestors)

Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This was a partial and single-blind study. During the in-clinic product use period, subjects knew whether the product was a pouch or MST product but were blinded to the strength of the oral TDN product they used on a given day.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a 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 and subjects' OBMST product. A 6x6 Latin Square was used for the randomization, with the following sequences: Sequence 1 = ABFCED, Sequence 2 = BCADFE, Sequence 3 = CDBEAF, Sequence 4 = DECFBA, Sequence 5 = EFDACB, and Sequence 6 = FAEBDC. For pharmacokinetics analysis a linear mixed model for analysis of variance was performed on the natural log-transformed nicotine baseline-adjusted PK parameters Cmax(0-180) and AUC(0-180). For subjective effects measures a linear mixed model for analysis of variance was performed on each of the Emax-UC parameter values for the 2 items in the Smokeless Urge and Craving Questionnaire and for each of the Emax-PE parameter values for the 7 items in the Product Effects Questionnaire.

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: November 15, 2024
• Study Start: February 6, 2023
• Primary Completion: May 10, 2023
• Study Completion: February 8, 2024
• Last Updated: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)