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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 4
- 主要终点
- Plasma Nicotine (ng/mL)
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 22 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Self-affirmed adult consumers of MST with usual brand of COPENHAGEN Fine Cut, or COPENHAGEN Long Cut, SKOAL Long Cut, or GRIZZLY Long Cut MST products in Mint, Natural, and Wintergreen flavor variants (and a single Straight variant; consumption of at least ½ can per day in the 30 days prior to Screening) for at least 12 months prior to Check-in; subjects cannot reject any of the flavor variants. Brief periods (i.e., up to 7 consecutive days) of non-MST usage within 90 days before Check-in (e.g., due to illness, participation in a clinical study where tobacco use was prohibited) will not be exclusionary at the discretion of the Investigator.
- •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.
- •Willing to comply with the requirements of the study.
- •Willing and able to use all oral TDN study products for at least 45 minutes.
排除标准
- •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.
- •Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator. Fasting serum glucose of 126 mg/dL [7 mmol/L] is exclusionary. One re-check may be performed for values greater than or equal to 126 mg/dL but less than 200 mg/dL.
- •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.
- •Allergic to or cannot tolerate mint, cool mint, spearmint, or peppermint flavoring agents.
- •Any planned surgery from the time of Screening through the End-of-Study.
- •History of drug or alcohol abuse within 24 months prior to Check-in.
- •Fever (i.e., body temperature > 100.5 ͦ F) at Screening or Check-in. One re-check may be performed at the Investigator's discretion.
- •Systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 90 mmHg at Screening or Check-in, measured after being seated for at least 10 minutes. Two re-checks may be performed at the Investigator's discretion.
- •BMI greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.
- •Estimated glomerular filtration rate (eGFR) < 80 mL/minute (using the Modification of Diet in Renal Disease formula) at Screening.
- •Serum alanine aminotransferase (ALT) ≥ 1.5 times the upper limit of normal and/or aspartate aminotransferase (AST) ≥ 2.0 times the upper limit of normal at Screening.
- •Positive urine/breath screen for alcohol at Screening or Check-in.
- •Positive urine/saliva screen for any of the following drugs of abuse, regardless of the reason of use: amphetamines, opiates, cannabinoids, or cocaine at Screening or Check-in.
- •Female subjects who are pregnant (positive serum/urine pregnancy test at Screening, prior to the start of Follow-up Screening/Product Trial, or Check-in), lactating, or intend to become pregnant from Screening through the End-of-Study.
- •Use of medications known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to Check-in or during the study.
- •Use of antibiotic treatment within 2 weeks prior to Check-in.
- •Plasma donation within 7 days prior to Day
- •Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Day
- •Participation in a previous clinical study for an investigational drug, device, biologic, or for a tobacco product within 30 days prior to Check- in.
- •Participation in more than two Altria Client Services LLC (ALCS) sponsored studies within the past 12-month period prior to Check-in.
- •Subject or a first-degree relative (i.e., parent, sibling, child, spouse) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company.
- •Subject or a first-degree relative (i.e., parent, sibling, child, spouse) is a current employee of the study site.
结局指标
主要结局
Plasma Nicotine (ng/mL)
时间窗: Day 1 through Day 6
Maximum plasma nicotine concentration (Cmax) measured following the product use under controlled use conditions
Smokeless Urge and Craving Questionnaire
时间窗: Day 1 through Day 6
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.
Product Effects Questionnaire
时间窗: Day 1 through Day 6
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.
次要结局
未报告次要终点