Nordic Spirit Pouch Nicotine Pharmacokinetics Abuse Liability

Exclusion Criteria32

• Self-reported puffers (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).
• Any postponement of a quit attempt to participate in the study; or any attempts to quit smoking in the 3 months prior to Check-in).
• Poor dentition that prevents participant from using nicotine gum.
• History or presence of any type of malignant tumor or 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 interfere with the absorption, distribution, metabolism, or excretion of nicotine or jeopardize the safety of the participant or impact the validity of the study results.
• Current evidence or any history of congestive heart failure.
• Any other condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study, or unable or unwilling to comply with the study procedures.
• All prescribed medication must have been stopped at least 14 days prior to (first) admission to the clinical site. An exception is made for hormonal contraceptives that may be used throughout the study.
• All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's wort) must have been stopped at least 14 days prior to (first) admission to the clinical site. An exception is made for acetaminophen that is allowed up to admission to the clinical site.
• Clinically significant abnormal vital sign, physical examination (including oral cavity and oropharynx), medical history, or clinical laboratory finding(s), in the opinion of the Investigator.
• Positive test for HIV-1 or HIV-2; or HBsAg or HCV consistent with current infection at screening.
• Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator. Fasting plasma glucose \>126 mg/dL (7 mmol/L) is exclusionary. One recheck may be performed for fasting plasma glucose values \>126 mg/dL but \<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.
• History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study through EOS.
• History of alcohol abuse or drug abuse within 24 months prior to Check-in.
• Consumption of alcohol-containing food or beverages within 48 hours prior to Check-in.
• Positive screen for alcohol (breath or urine) or drugs of abuse (urine), regardless of the reason of use at screening or Check-in, with the exception of positive results for THC. If positive for THC at check-in (Day -1), a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of the Investigator.
• Fever (i.e., body temperature \>100.5°F) at screening or Check-in; 1 recheck may be performed at the Investigator's discretion.
• BMI \<18.0 kg/m2 or \>40.0 kg/m2 at screening.
• Estimated glomerular filtration rate \<80 mL/minute using the CKD-EPI formula (Medscape) at screening.
• Serum alanine aminotransferase ≥1.5 times the upper limit of normal and/or aspartate aminotransferase ≥2.0 times the upper limit of normal at screening; 1 recheck may be performed at the Investigator's discretion.
• Female participants who are pregnant (positive pregnancy test at screening or Check-in), lactating, or intend to become pregnant from screening through EOS.
• Use of prescription or OTC bronchodilator medication (e.g., inhaled or oral β-agonists) for treatment of any illness within 12 months prior to Check-in.
• Use of antibiotics within 2 weeks prior to Check-in.
• Use of medications known or 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, and tioconazole, tranylcypromine) within 14 days or 5 half lives of the medication, whichever is longer, prior to Check-in.
• Has taken other investigational drugs/products or participated in any clinical study for an investigational drug, device, biologic, or for a tobacco product within 30 days or 5 half-lives (if known) of the investigational product's PK, PD, or biological activity (if known), whichever is longer, prior to first administration of study product in this study or is currently participating in another clinical study prior to Check-in.
• Has received a vaccination within 14 days prior to Check-in.
• Plasma donation within 7 days prior to Day 1.
• Donation of ≥1 unit of blood or blood products (with the exception of plasma as noted), had significant blood loss \>450 mL, or received whole blood or a blood product transfusion within 56 days prior to Check-in.
• Strenuous activity (as assessed by the Investigator) within 48 hours prior to Check-in.
• Participant 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.
• Participant or a first-degree relative (i.e., parent, sibling, child, spouse) is a current employee of the study site or service provider.
• Unwilling or unlikely to comply with the requirements of the study