NCT06777784

Brief Summary

This is a two-site, open-label, randomized, 8-way cross-over study designed to evaluate elements of abuse liability (AL) including subjective effects and physiological measures (pharmacodynamics \[PD\]) and plasma nicotine uptake (pharmacokinetics \[PK\]) during and following ad libitum use of the study investigational products (IPs) by generally healthy smokers.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Feb 2025

Shorter than P25 for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 10, 2025

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 16, 2025

Completed
18 days until next milestone

Study Start

First participant enrolled

February 3, 2025

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 5, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 5, 2025

Completed
Last Updated

December 23, 2025

Status Verified

December 1, 2025

Enrollment Period

1 month

First QC Date

January 10, 2025

Last Update Submit

December 22, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • AUECPL 5-240

    area under the effect curve (AUEC) for PL (VAS score-versus-time)

    5 minutes to 240 minutes

  • Emax PL

    maximum effect (maximum PL VAS score after the start of IP use)

    240 minutes

Study Arms (8)

Product usage order ANBGCFDE

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order BACNDGEF

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order CBDAENFG

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order DCEBFAGN

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order EDFCGBNA

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order FEGDNCAB

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order GFNEADBC

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order NGAFBECD

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Interventions

Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Cool Mint 6 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Cool Mint 12 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Cool Mint 15 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Smooth 6 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Wintergreen 6 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Modern Nicotine Oral Product Dragon Fruit 6 mg Nicotine

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Nicorette® White Ice Mint 4 mg nicotine gum

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Eligibility Criteria

Age21 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
  • Generally healthy males or females, 21 to 60 years of age, inclusive, at the time of consent.
  • Smokes combustible, filtered, non-menthol or menthol cigarettes, 83 mm to 100 mm in length as primary source of tobacco.
  • Smokes an average of at least 10 cigarettes per day (CPD) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (prior to 30 days of Screening), or clinical study participation (prior to 30 days of Screening) will be allowed at the discretion of the an investigator.
  • Smokers who also use ST products (e.g., moist snuff, snus, modern oral), and have used ST within 30 days prior to screening, will be enrolled.
  • Agrees to smoke the same UB cigarette throughout the study period. The UB cigarette is defined as the reported cigarette brand and style currently smoked most frequently by the subject.
  • Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening and at check-in (Day -1).
  • Positive urine cotinine test (e.g., \>200 ng/mL) via dipstick at Screening.
  • Response at Screening to the Fagerström Test for Nicotine Dependence (FTND) Question 1 ("How soon after you wake up do you smoke your first cigarette?") is either "Within 5 minutes" or "6-30 minutes" (Heatherton et al., 1991).
  • Willing to use the UB cigarette, Velo PLUS IPs, and Nicorette® nicotine gum during the study period.
  • Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of eight Test Sessions.
  • Females must be willing to use a form of contraception acceptable to an investigator from the time of signing the ICF until End-of-Study. Examples of acceptable means of birth control are, but not limited to: a) Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy); b) physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide; c) non-hormone releasing intrauterine devices (IUD) or hormone-releasing IUDs (e.g., Mirena or Kyleena); d) vasectomized partner; or e) post-menopausal and not on hormone replacement therapy.
  • Agrees to an in-clinic confinement of ten days (nine nights).

You may not qualify if:

  • Allergic to or cannot tolerate mint or wintergreen flavoring agents.
  • Individuals or their family members that have ongoing litigation with tobacco company(ies)
  • Have used electronic nicotine delivery system (e.g., Vuse Alto, JUUL) or tobacco heating device (e.g., iQOS) within the last 30 days prior to screening.
  • Presence of clinically significant uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, psychiatric, hematological, neurological disease, or any other concurrent disease or medical condition that, in the opinion of an investigator, makes the study subject unsuitable to participate in this clinical study.
  • History, presence of, or clinical laboratory test results indicating diabetes.
  • Scheduled treatment for asthma currently or within the past consecutive 12 months prior to the Screening Visit. As-needed treatment, such as inhalers, may be included at an investigator discretion.
  • History or presence of bleeding or clotting disorders.
  • Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed.
  • Systolic blood pressure of \> 160 mmHg or a diastolic blood pressure of \> 95 mmHg, measured after being seated for five minutes at Screening or at check-in Day -1.
  • Weight of ≤ 110 pounds at screening or at check-in.
  • Hemoglobin level is \< 12.5 g/dL for females or \< 13.0 g/dL for males at Screening.
  • Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
  • Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
  • Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), or lobelia extract within (≤) 30 days prior to signing the informed consent.
  • Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or self-reports a previous quit attempt within (≤) 30 days prior to signing the informed consent.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

AMR Lexington

Lexington, Kentucky, 40509, United States

Location

AMR Knoxville

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

SmokingTobacco Use

Interventions

HTR3D protein, human

Condition Hierarchy (Ancestors)

Behavior

Study Officials

  • Brian Keyser, PhD

    Reynolds American

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2025

First Posted

January 16, 2025

Study Start

February 3, 2025

Primary Completion

March 5, 2025

Study Completion

March 5, 2025

Last Updated

December 23, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations