A Study to Assess Nicotine Uptake From Electronic Nicotine Delivery System Products

Official title

An Open-Label, Randomized, 8-way Crossover Study to Assess Elements of Abuse Liability Electronic Nicotine Delivery System Products in Adult Smokers

Overview

This will be a randomized, open-label, 8-way crossover, single-site 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 electronic nicotine delivery system (ENDS) investigational products (IPs). The study will be conducted in a confinement setting among generally healthy adult smokers of combustible cigarettes and dual users of cigarettes and ENDS products.

Detailed description

Adult smokers of filtered menthol and/or non-menthol cigarettes and smokers who also use ENDS will be recruited into this study to evaluate elements of ENDS IP AL, in comparison to participant's usual brand (UB) cigarette.

Potential participants will undergo a pre-screening interview followed by a Screening Visit within 28 days prior to enrollment, randomization, and study confinement to assess eligibility.

Eligible participants will be scheduled for a check-in and randomization visit. At this visit, eligibility will be reconfirmed prior to randomization to a product use sequence, based on a Williams design. Participants will then enter a 10-day, 9-night confinement period at the clinical site.

On study Day -1, participants will enter a product familiarization period during which they will be required to use each of three ENDS IP (Product C \[Glacier Menthol 5%, device, 6.5W\], Product F \[Fresh Mint 5%, device, 6.5W\], and Product H \[Fresh Mint 5%, device, 6.5W\]) at least once. Use of each ENDS IP during the familiarization period will be approximately 5 minutes. After completing this familiarization, participants will be permitted to smoke their UB cigarettes ad libitum. Participants who also use other tobacco and/or nicotine-containing products such as ENDS, smokeless tobacco or modern oral nicotine products in addition to their UB cigarettes will not have access to those products during the study.

Following the product familiarization period, participants will enter a product acclimation period beginning on Day 1 and each day prior to a test session. During each daily product acclimation period, participants will be required to use their randomized IP assigned for use in the subsequent day's test session (excluding their UB cigarette) at least four times. For each ENDS IP, each product use period during the daily acclimation period will last approximately 5 minutes. After completing this requirement, participants will be permitted to smoke their UB cigarettes ad libitum. Pharmacy logs will be used to capture information on product usage during the product familiarization and acclimation periods.

At the end of the product acclimation period and ad libitum use of the participant's UB cigarette, participants will abstain from use of all tobacco- and nicotine-containing products for a minimum of 12 hours prior to each test session occurring on the following day. In addition, participants will be required to abstain from any caffeine-containing products for 4 hours prior to the start of each test session through the end of the test session.

Starting on Day 2 and continuing through Day 9, each participant will participate in eight consecutive daily test sessions, evaluating one IP per session. Over the course of the study, each participant will evaluate a total of eight IPs: seven ENDS IPs and a high-AL comparator (the participant's UB cigarette).

During each test session, subjective effects questionnaire responses will be collected before, during, and after each product use. Blood samples will then be collected for plasma nicotine PK assessments, and, subsequently, the collection of physiological measures after IP use. Table 1-1 and Table 1-2 outline the schedule of study procedures, and the timing and sequence of activities involving behavioral questionnaires, PK blood sampling and physiological measurements, respectively.

The active period of each test session will start with the assigned IP use initiation and last approximately 4 hours during and following product use. During each test session, participants will be allowed approximately 5 minutes of smoking one UB cigarette and approximately 5 minutes of ENDS IP use based on the product use sequence to which participants will be randomized.

Participants' use of the ENDS IP will be self-defined during the 5-minute ad libitum IP use session; specific parameters around puff duration, volume, inter puff interval, and quantity will not be prescribed.

ENDS IP e-liquid cartridges will be weighed within 4 hours before and after the test session on Days 2 - 9.

Participant general health and well-being will be monitored throughout the study by the Principal Investigator (PI) or qualified designee by adverse events (AEs) assessments, vital sign measurements, physical examinations (including an oral examination), and clinical laboratory tests. The Medical Monitor will be available for consultation throughout the study and for any necessary follow-up after discharge.

Interventions

• Other Golden Tobacco Chill 5% (4) 6.5W
  Golden Tobacco Chill 5% (4) 6.5W
• Other Glacier Menthol 5% (4) 6.5W
  Glacier Menthol 5% (4) 6.5W
• Other Fresh Mint 5% (4) 6.5W
  Fresh Mint 5% (4) 6.5W
• Other Fresh Mint 5% (4) 4.5W
  Fresh Mint 5% (4) 4.5W
• Other Fresh Mint 5% (3) 6.5W
  Fresh Mint 5% (3) 6.5W
• Other Fresh Mint 5% (3) 5.5W
  Fresh Mint 5% (3) 5.5W
• Other Fresh Mint 5% (2) 6.5W
  Fresh Mint 5% (2) 6.5W
• Other Usual Brand Cigarette
  Usual Brand Cigarette

Primary outcome measures

• AUC nic 3-240 [Time frame: 3 minutes to 240 minutes]
• Emax PL [Time frame: 240 minutes]

Eligibility criteria

Inclusion criteria

• Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
• Generally healthy male or female, 21 to 60 years of age, inclusive, at the time of consent.
• Expired breath carbon monoxide level is ≥ 10 ppm and ≤ 100 ppm at Screening.
• Positive urine cotinine test at Screening.
• Smokes combustible filtered, menthol or non-menthol cigarettes, 83 mm to 100 mm in length.
• Agrees to smoke same UB cigarette throughout the study period. UB cigarette is defined as the cigarette brand style currently smoked most frequently by the participant.
• Participants must meet one (a or b) of the following tobacco use conditions:

a. Sole smoker of filtered menthol or non-menthol cigarettes who self reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (more than 30 days prior to Screening), or clinical study participation (more than 30 days prior to Screening) will be allowed at the discretion of an investigator b. Dual user of cigarettes and ENDS who self-reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening Visit. Brief periods of abstinence more than 30 days prior to screening due to illness, quit attempt or clinical study participation will be allowed at the discretion of an investigator, and ii. Using a nicotine-containing ENDS (cartridge or a tank system). NOTE: Cigarette smokers or ENDS users who also use other tobacco- or nicotine-containing products (e.g., smokeless tobacco, and modern oral nicotine products) on no more than one day per week will not be excluded from study participation.

• 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."
• Willing to use only UB cigarettes and ENDS IPs during the study period.
• Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each test session.
• Females must be willing to use a form of contraception acceptable to an investigator from the time of signing informed consent until End-of-Study. Examples of acceptable means of birth control include, but are not limited to:

• Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy);
• Physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide;
• Non-hormone releasing intrauterine devices (IUDs) or hormone-releasing IUDs (e.g., Mirena or Kyleena);
• Vasectomized partner;
• Post-menopausal and not on hormone replacement therapy; or
• Sexual abstinence, defined as refraining from intercourse, when this is in line with the preferred and usual lifestyle of the participant.
• Males must use an acceptable method of birth control from Day -1 "check-in" until the end of the study, unless they have had a vasectomy or are abstinent from heterosexual intercourse, or their female partner is not able to bear children.
• Agrees to in-clinic confinement of 10 days and 9 nights.

Exclusion criteria

• 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 participant unsuitable to participate in this clinical study.
• History, presence of, or clinical laboratory test results indicating diabetes.
• Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg, measured after being seated for five minutes at Screening and at check-in Day -1.
• Weight of ≤ 110 pounds (≤ 50.0 kg) at Screening.
• Hemoglobin level is < 12.5 g/dL for females or <13.0 g/dL for males at Screening.
• 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's discretion.
• Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• 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.
• Must not be a current regular user (i.e., > 5 times per month) of any tobacco products other than cigarettes or ENDS within the last 6 months prior to screening.
• 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®), GLP-1 agonists (e.g., Wegovy®, Mounjaro®, and Ozempic®), or lobelia extract within ≤ 30 days prior to the signing of informed consent.
• History or presence of bleeding or clotting disorders.
• Use of daily aspirin (≥ 325 mg) or other daily anticoagulants.
• Whole blood donation within 8 weeks (≤ 56 days) prior to the signing of informed consent and between Screening and check-in Day -1.

NOTE: Participants will be advised against scheduling a whole blood donation for at least 7 days following study completion.

• Plasma donation within ≤ 7 days prior to the signing of informed consent and between Screening and check-in Day -1.

NOTE: Participants will be advised against scheduling a plasma donation for at least 7 days following study completion.

• Participation in another clinical trial within ≤ 30 days prior to the signing of informed consent. The 30-day window for each participant will be derived from the date of the last study event in the previous study to the time of signing the ICF in the current study.
• Females who have a positive pregnancy test at Screening or check-in on Day -1, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
• Individuals ≥ 35 years of age currently using systemic, estrogen-containing contraception or hormone replacement therapy.
• A positive drug screen or alcohol test (urine or breath) at Screening or at check-in (Day -1), with the exception of positive results for tetrahydrocannabinol (THC). If positive for THC at check-in, a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of an investigator.
• Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or a previous quit attempt within ≤ 30 days prior to the signing of the ICF.
• Has a significant history of alcoholism or drug abuse within 24 months prior to Screening, as determined by an investigator, or has a positive alcohol test at Screening or check-in on Day -1.
• Employed by a tobacco or nicotine company, the study site, or handles tobacco- or nicotine-containing products as part of their job.
• Individuals or their family members that have ongoing litigation with tobacco company(ies).
• Determined by an investigator to be inappropriate for this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07739797 · IHI263101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗