Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of Nicotine as Assessed by the Cmax (20-min Directed Bout)
研究概览
简要总结
The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum.
详细描述
The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum. Blood specimens will be obtained throughout the sessions to characterize the pharmacokinetics of nicotine and various pharmacodynamic outcomes (subjective drug effects, tobacco withdrawal symptoms, vital signs) will also be assessed. These procedures will be completed 7 separate times (on separate visits) by each participant (sessions will be separated by at least 48 hours).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Care Provider)
盲法说明
Double-blinded
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •≥ 21 years old
- •good general health based on screening procedures (e.g., physical exam, blood testing)
- •vital signs in normal range (resting heart rate less than 100bpm, systolic blood pressure less than 150mmHg, diastolic blood pressure less than 90mmHg)
- •negative urine test for illicit drug use (excluding THC) and negative breath alcohol test at screening and before each session
- •self-report currently smoking daily
- •self-report at least a one year history of regular smoking
- •exhaled breath CO greater than or equal to 10ppm and urine cotinine greater than 100 ng/ml at screening
- •meet criteria for at least mild tobacco use disorder
- •no self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days
- •no self-reported prior use of novel oral nicotine pouches
- •exhaled breath CO less than 10 ppm upon arrival for each study session.
排除标准
- •Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month
- •Current use of over-the-counter (OTC) drugs, supplements/vitamins, or prescription medications that, in the opinion of the investigators or medical staff, will impact safety
- •Use of cannabis >4 times per week
- •History of or current significant medical condition that, in the opinion of the investigators or medical staff, will impact safety
- •Current psychiatric condition or substance use disorder (aside from tobacco use disorder) that, in the opinion of the investigators or medical staff, will impact safety or study outcomes
- •Women who are pregnant, planning to become pregnant, or are breast-feeding
- •Currently seeking treatment to quit smoking or currently using a nicotine/tobacco cessation product.
- •Enrollment in another clinical trial in the past 30 days
研究组 & 干预措施
Original/Tobacco Flavored Pouch (high nicotine dose)
participants will use a tobacco flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
Mint/Menthol Flavored Pouch (low nicotine dose)
participants will use a mint/menthol flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
Own brand cigarettes
participants will smoke participants' own brand of cigarettes under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Cigarette (Other)
Original/Tobacco Flavored Pouch (low nicotine dose)
participants will use a tobacco flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
Fruit Flavored Pouch (low nicotine dose)
participants will use a fruit flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
Fruit Flavored Pouch (high nicotine dose)
participants will use a fruit flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
Mint/Menthol Flavored Pouch (high nicotine dose)
participants will use a mint/menthol flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
干预措施: Nicotine (Other)
结局指标
主要结局
Pharmacokinetics of Nicotine as Assessed by the Cmax (20-min Directed Bout)
时间窗: 0 to 1 hour
Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Maximum concentration (Cmax), is the highest plasma nicotine concentration reached during a session and provides important insight into the abuse liability of a tobacco product. Bout 1 (20min directed use) Cmax was calculated based on post-baseline blood timepoints which include 10 minutes, 20 minutes, 30 minutes, and 1 hour after bout 1 dosing.
Pharmacokinetics of Nicotine as Assessed by the AUC (20 Min Directed Bout)
时间窗: 0 to 1 hour
Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Area under the curve (AUC), represents the total nicotine exposure during an entire nicotine use period and provides important insight into the abuse liability of a tobacco product. Data is reported as the mean (SD) change from baseline. Bout 1 (20min directed use) AUC was calculated based on post-baseline blood timepoints which include 10 minutes, 20 minutes, 30 minutes, and 1 hour after bout 1 dosing.
Peak Change From Baseline Subjective Ratings of "Like Drug Effect" as Assessed by the Drug Effect Questionnaire
时间窗: Up to 6.5 hours
The DEQ will be used to obtain subjective ratings of "like drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater liking. Data is reported as mean (SD) change from baseline. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.
Subjective Ratings of "Pleasant Drug Effect" as Assessed by the Drug Effect Questionnaire
时间窗: Up to 6.5 hours
The DEQ will be used to obtain subjective ratings of "pleasant drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater "pleasant drug effect". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.
Subjective Ratings of "Take Again" as Assessed by the Drug Effect Questionnaire
时间窗: Up to 6.5 hours
The DEQ will be used to obtain subjective ratings of "take again". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation, with higher score indicating greater "take again" rating. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.
Subjective Ratings of "Urge to Smoke" as Assessed by the Hughes-Hatsukami Withdrawal Questionnaire (Change From Baseline)
时间窗: Up to 6.5 hours
The HHWS will be used to obtain subjective ratings of "urge to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater "urge to smoke". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.
Subjective Ratings of "Craving to Smoke" as Assessed by the Hughes-Hatsukami Withdrawal Questionnaire (Change From Baseline)
时间窗: Up to 6.5 hours
The HHWS will be used to obtain subjective ratings of "craving to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation, with higher score indicating greater "craving to smoke". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.
次要结局
- Pharmacokinetics of Nicotine as Assessed by the Tmax(Up to1 hour)
- Tobacco Withdrawal Symptoms as Assessed by the Tiffany-Drobes QSU Brief-Factor 1 (Change From Baseline)(Up to 6.5 hours)
- Tobacco Withdrawal Symptoms as Assessed by the Tiffany-Drobes QSU Brief-Factor 2 (Change From Baseline)(6.5 hours)
- Topography as Assessed by the Total Time of Use(2 hours)
- The Direct Effects of Nicotine Scale (DENS) (Change From Baseline)(6.5 hours)
- Perceived Strength of Effects as Assessed by the Drug Effect Questionnaire(Up to 6.5 hours)
- Negative and Aversive Effects as Assessed by the Drug Effect Questionnaire(Up to 6.5 hours)