Tobacco Use
Conditions
Keywords
Tobacco, Smoking
Brief summary
The purpose of this study is to generate evidence regarding the extent of reduction in exposure to selected HPHCs in adult smokers switching to on!® NPs. The study intends to determine changes in exposure to selected HPHCs by measuring biomarkers in adult smokers who completely switch from smoking to use of on!® NP compared to those who continue smoking cigarettes or stop using all tobacco products.
Detailed description
This is an open-label, randomized, 5 parallel-group clinical study evaluating changes in exposure to selected harmful and potentially harmful constituents (HPHCs) and product use behavior in adult smokers who are randomly assigned to 1 of the 5 groups; continue smoking, partially or completely switch to oral tobacco-derived nicotine products, or stop using any tobacco products for 7 days.
Interventions
OTHEROTDN Product 1
Mint on!® 2 mg nicotine pouches
OTHEROTDN Product 2
Mint on!® 4 mg nicotine pouches
OTHEROTDN Product 3
Mint on!® 8 mg nicotine pouches
OTHERNo Tobacco
subjects completely stop all tobacco product usage for 7 days
Sponsors
Covance
Altria Client Services LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntary consent to participate in this study documented on the signed ICF 2. Smoking history (self-reported at screening) of an average of at least 10 but no more than 30 factory-manufactured combustible cigarettes (either menthol or non-menthol) daily for at least 12 months prior to screening. Brief periods (ie, up to 7 consecutive days) of non-smoking during the 3 months prior to screening (eg, due to illness or participation in a study where smoking was prohibited) will be permitted 3. Positive urine cotinine (≥ 500 ng/mL) at screening 4. Female subjects who are heterosexually active and of childbearing potential (eg, neither surgically sterile at least 6 months prior to check-in nor postmenopausal with amenorrhea for at least 12 months prior to check-in with follicle-stimulating hormone \[FSH\] levels consistent with postmenopausal status) must have been using one of the following forms of contraception for the time period indicated and agree to continue using it through completion of the study: * Hormonal (eg, oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to check-in, double barrier (ie, condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to check-in, an intrauterine device for at least 4 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. 5. 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 (including Essure® or similar nonsurgical sterilization procedures); bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy Or be postmenopausal with amenorrhea for at least 12 months prior to check-in and have FSH levels consistent with postmenopausal status 6. Willing to comply with the requirements of the study 7. Willing to use all 3 on!® NP after the Product Trial at check-in 8. Willing and able to abstain from cigarettes from Day 1 through the end of the study (EOS) 9. Healthy adult males and females, 21 to 65 years of age, inclusive at screening, with subjects aged 46 to 65 years being fully vaccinated for COVID-19 (SARS-CoV-2) at least 14 days before the screening visit.
Exclusion criteria
1. Use of any type of tobacco- or nicotine-containing products other than manufactured cigarettes (eg, e-vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to check-in 2. Self-reported puffers (ie, adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale) 3. Planning to quit smoking in the next 30 days (from screening visit) 4. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, 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 5. Clinically significant abnormal findings on the vital signs, physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results, in the opinion of the investigator 6. Positive test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at screening 7. History or presence of any type of malignant tumors 8. Current evidence or any history of congestive heart failure 9. Diabetes mellitus (fasting glucose ≥126 mg/L \[7 mmol/L\]) that is not controlled by diet/exercise alone, in the opinion of the investigator 10. An acute illness (eg, upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to check-in 11. Dentition that prevents subjects from using on!® NP products 12. Allergic to or cannot tolerate mint flavoring agents or phenylalanine 13. Any planned surgery from the time of screening through EOS 14. History of drug or alcohol abuse within 24 months prior to check-in 15. Fever (ie, body temperature \>100.5°F) at screening or check-in. One recheck may be performed at the investigator's discretion 16. Body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at screening 17. Systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 90 mmHg at screening or check-in, measured after being seated for at least 5 minutes. One recheck may be performed at the investigator's discretion 18. Estimated creatinine clearance (by Cockcroft-Gault equation) \< 80 mL/minute at screening 19. Serum alanine aminotransferase ≥1.5 times the upper limit of normal and/or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening 20. Positive screen for alcohol (breath) or any of the following drugs of abuse (urine), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or check-in 21. Female subjects who are pregnant (positive serum pregnancy test at screening or urine pregnancy test at check-in), lactating, or intend to become pregnant from screening through EOS 22. Use of prescription or over-the-counter bronchodilator medication (eg, inhaled or oral ß-agonists) within 12 months prior to check-in 23. Use of medications or foods 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, grapefruit, 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 24. Use of antibiotic treatment within 2 weeks prior to check-in 25. Plasma donation within 7 days prior to check-in 26. 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 check-in 27. Participation in a previous clinical study for an investigational drug, device, biologic, or a tobacco product within 30 days prior to check-in 28. Participation in 2 or more Altria Client Services (ALCS) studies within the past 12-month period prior to check-in 29. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company 30. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current employee of the study site 31. Positive result for coronavirus disease (COVID)-19 (SARS-CoV-2) test at screening or check-in 32. One or more yes answers to any of the questions on the COVID-19 (SARS-CoV-2) screening questionnaire (provided by the study site) at screening or check-in. 33. Have been diagnosed with major depressive disorder or have a history of suicide attempt.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-aminonaphthalene (2-AN) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 4-aminobiphenyl (4-ABP) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-hydroxyethylmercapturic acid (HEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted cyanoethylmercapturic acid (CEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted S-phenylmercapturic acid (SPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 3-hydroxypropylmercapturic acid (3-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-hydroxypropylmercapturic acid (2-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoylethyl) cysteine (AAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-1-cysteine (GAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-hydroxybutenylmercapturic acid (2-MHBMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted Nicotine Equivalents (NE) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during the 24 hours was converted to 24-hour urine volume using the assumed density of 1 gram (g) equals 1 milliliter (mL). The amount of biomarker was calculated as follows: NE concentration (μg/mL) = (nicotine \[ng/mL\]/162.23 \[mg/mmol\] + nicotine-gluc \[ng/mL\]/338.36 \[mg/mmol\] + cotinine \[ng/mL\]/176.22 \[mg/mmol\] + cotinine-gluc \[ng/mL\]/352.34 \[mg/mmol\] + trans-3'-hydroxycotinine \[ng/mL\]/192.22 \[mg/mmol\] + trans-3'-hydroxycotinine-gluc \[ng/mL\]/368.34 \[mg/mmol\]) × 162.23 (mg/mmol) × 1 μg/1000 ng Adjusted Nicotine equivalents (mg NE/g creatinine) = NE concentration (μg/mL) × 100 / Creatinine concentration (mg/dL) Absolute change from baseline = Post Randomization Value - Baseline Value |
| 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-OH-Fluorene (2-OH-Flu) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 2-Naphthol (2-OH-Nap) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 1-OH-Phenanthrene (1-OH-Phe) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 3-hydroxybenzo\[a\]pyrene (3-OH-B\[a\]P) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urine mutagenicity (Rev/24h) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. Measurement results are reported as revertants/μL. Urine mutagenicity count in the 24-hour urine was calculated as: Urine mutagenicity (revertants/250 mL) = Urine mutagenicity (revertants/μL) x 1000V, where V is the volume after concentration in mL Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x \[24h urine volume(mL) ÷ V\], where V is the volume in mL of urine sample used for the mutagenicity test |
| 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected over 24 hours on Day -1 (baseline) and Day 7 | Summary of 24-hour urinary creatinine-adjusted 1-hydroxypyrene (1-OH-Pyr) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value |
| Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7 | Summary of blood carboxyhemoglobin (%) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. The absolute change from baseline of urine biomarker amount excreted in 24 hours and blood biomarker concentration will be calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value where Baseline = Day -1 |
| Summary of Cigarettes Smoked Per Day (CPD) | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study | The number of cigarettes smoked per day (CPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Subjects in NP2, NP4, NP8 and NT groups were not allowed to use cigarettes starting at Day 1. |
| Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study | The number of nicotine pouches used per day (NPPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study. |
| Summary of Average Number of Nicotine Pouches Per Use | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study | The average number of nicotine pouches per use occasion (NPPU) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study. |
| Summary of Average Duration of Each Nicotine Pouch Use | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study | The average duration (in minutes) of each nicotine pouch use from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study. |
Countries
United States
Participant flow
Pre-assignment details
After screening, subjects who met eligibility criteria but were not needed once sample size objectives were met, were discontinued. The remaining subjects participated in a brief Product Use Trial to allow them to become accustomed to the products prior to randomization. Subjects who did not meet the randomization criteria after completing the Product Use Trial were discontinued; these subjects are included in the safety population but were not assigned to a study group.
Participants by arm
| Arm | Count |
|---|---|
| Not Assigned Only include subjects that enrolled in the study but dropped prior to randomization. This group includes subjects who participated in the Product Trial Period but withdrew before randomization. | 2 |
| Group 1 (CC) Subjects will be asked to continue smoking their UBCs ad libitum for 7 days. | 29 |
| Group 2 (NP2) Subjects will exclusively use 2 mg NP, using at least 3 pouches per day for 7 days.
OTDN Product 1: Mint on!® 2 mg nicotine pouches | 28 |
| Group 3 (NP4) Subjects will exclusively use 4 mg NP, using at least 3 pouches per day for 7 days.
OTDN Product 2: Mint on!® 4 mg nicotine pouches | 30 |
| Group 4 (NP8) Subjects will exclusively use 8 mg NP, using at least 3 pouches per day for 7 days.
OTDN Product 3: Mint on!® 8 mg nicotine pouches | 30 |
| Group 5 (NT) Subjects will completely stop all tobacco product usage for 7 days.
No Tobacco: subjects completely stop all tobacco product usage for 7 days | 29 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Failure to Meet Randomization Criteria | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Met Eligibility Criteria But Not Needed | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 | 0 | 5 | 6 |
Baseline characteristics
| Characteristic | Group 1 (CC) | Total | Group 5 (NT) | Not Assigned | Group 4 (NP8) | Group 3 (NP4) | Group 2 (NP2) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 7.51 | 34.2 years STANDARD_DEVIATION 7.4 | 35.5 years STANDARD_DEVIATION 7.29 | 36.0 years STANDARD_DEVIATION 12.73 | 31.7 years STANDARD_DEVIATION 6.53 | 35.9 years STANDARD_DEVIATION 8.49 | 33.6 years STANDARD_DEVIATION 6.73 |
| Body Mass Index (kg/m^2) | 30.05 kg/m^2 STANDARD_DEVIATION 5.528 | 29.90 kg/m^2 STANDARD_DEVIATION 5.925 | 29.80 kg/m^2 STANDARD_DEVIATION 5.687 | 30.87 kg/m^2 STANDARD_DEVIATION 0.813 | 28.94 kg/m^2 STANDARD_DEVIATION 6.077 | 30.35 kg/m^2 STANDARD_DEVIATION 6.336 | 30.42 kg/m^2 STANDARD_DEVIATION 6.242 |
| Body Weight (kg) | 88.67 kg STANDARD_DEVIATION 19.968 | 89.39 kg STANDARD_DEVIATION 19.971 | 88.74 kg STANDARD_DEVIATION 19.284 | 89.55 kg STANDARD_DEVIATION 14.213 | 85.82 kg STANDARD_DEVIATION 19.027 | 91.28 kg STANDARD_DEVIATION 20.291 | 92.61 kg STANDARD_DEVIATION 21.949 |
| Cigarettes per Day | 16.03 Cigarettes per day STANDARD_DEVIATION 5.519 | 16.34 Cigarettes per day STANDARD_DEVIATION 5.66 | 16.69 Cigarettes per day STANDARD_DEVIATION 5.439 | 16.50 Cigarettes per day STANDARD_DEVIATION 4.95 | 16.57 Cigarettes per day STANDARD_DEVIATION 6.372 | 16.23 Cigarettes per day STANDARD_DEVIATION 5.425 | 16.14 Cigarettes per day STANDARD_DEVIATION 5.848 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 145 Participants | 28 Participants | 2 Participants | 30 Participants | 30 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fagerström test - Total score | 4.7 points STANDARD_DEVIATION 1.37 | 4.8 points STANDARD_DEVIATION 1.83 | 5.4 points STANDARD_DEVIATION 1.84 | — | 4.4 points STANDARD_DEVIATION 1.92 | 5.1 points STANDARD_DEVIATION 2.12 | 4.5 points STANDARD_DEVIATION 1.71 |
| Height (cm) | 171.41 cm STANDARD_DEVIATION 10.442 | 172.73 cm STANDARD_DEVIATION 9.6 | 172.32 cm STANDARD_DEVIATION 9.781 | 170.00 cm STANDARD_DEVIATION 11.314 | 172.35 cm STANDARD_DEVIATION 10.216 | 173.42 cm STANDARD_DEVIATION 8.53 | 174.16 cm STANDARD_DEVIATION 9.357 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 54 Participants | 10 Participants | 0 Participants | 16 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 91 Participants | 17 Participants | 2 Participants | 14 Participants | 17 Participants | 20 Participants |
| Sex: Female, Male Female | 13 Participants | 64 Participants | 12 Participants | 1 Participants | 13 Participants | 13 Participants | 12 Participants |
| Sex: Female, Male Male | 16 Participants | 84 Participants | 17 Participants | 1 Participants | 17 Participants | 17 Participants | 16 Participants |
| Years of Smoking | 16.15 years STANDARD_DEVIATION 9.228 | 15.80 years STANDARD_DEVIATION 8.579 | 15.94 years STANDARD_DEVIATION 8.304 | 10.00 years STANDARD_DEVIATION 0 | 14.27 years STANDARD_DEVIATION 7.924 | 16.71 years STANDARD_DEVIATION 10.495 | 15.98 years STANDARD_DEVIATION 6.784 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 29 | 0 / 28 | 0 / 30 | 0 / 30 | 0 / 29 |
| other Total, other adverse events | 0 / 2 | 5 / 29 | 15 / 28 | 9 / 30 | 15 / 30 | 12 / 29 |
| serious Total, serious adverse events | 0 / 2 | 0 / 29 | 0 / 28 | 0 / 30 | 0 / 30 | 0 / 29 |
Outcome results
Primary
NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 363 ng/g | Standard Deviation 239 |
| Group 1 (CC) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -32.8 ng/g | Standard Deviation 67.6 |
| Group 1 (CC) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 330 ng/g | Standard Deviation 224 |
| Group 2 (NP2) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 67.8 ng/g | Standard Deviation 70 |
| Group 2 (NP2) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 274 ng/g | Standard Deviation 203 |
| Group 2 (NP2) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -206 ng/g | Standard Deviation 146 |
| Group 3 (NP4) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 73.2 ng/g | Standard Deviation 42.7 |
| Group 3 (NP4) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 312 ng/g | Standard Deviation 201 |
| Group 3 (NP4) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -239 ng/g | Standard Deviation 172 |
| Group 4 (NP8) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 293 ng/g | Standard Deviation 213 |
| Group 4 (NP8) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -228 ng/g | Standard Deviation 171 |
| Group 4 (NP8) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 64.7 ng/g | Standard Deviation 51 |
| Group 5 (NT) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 71.3 ng/g | Standard Deviation 62.2 |
| Group 5 (NT) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 392 ng/g | Standard Deviation 308 |
| Group 5 (NT) | NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -321 ng/g | Standard Deviation 290 |
p-value: <0.000195% CI: [15.9, 37]ANCOVA
p-value: <0.000195% CI: [17.1, 37.3]ANCOVA
p-value: <0.000195% CI: [14.9, 33.7]ANCOVA
p-value: <0.000195% CI: [10.8, 25.3]ANCOVA
p-value: 0.114895% CI: [93.7, 230]ANCOVA
p-value: 0.04495% CI: [101, 233]ANCOVA
p-value: 0.242295% CI: [87.8, 210]ANCOVA
Secondary
1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 1-OH-Phenanthrene (1-OH-Phe) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.218 μg/g | Standard Deviation 0.107 |
| Group 1 (CC) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.0142 μg/g | Standard Deviation 0.0517 |
| Group 1 (CC) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.203 μg/g | Standard Deviation 0.108 |
| Group 2 (NP2) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0804 μg/g | Standard Deviation 0.0397 |
| Group 2 (NP2) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.162 μg/g | Standard Deviation 0.0816 |
| Group 2 (NP2) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.0818 μg/g | Standard Deviation 0.0592 |
| Group 3 (NP4) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0804 μg/g | Standard Deviation 0.0397 |
| Group 3 (NP4) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.172 μg/g | Standard Deviation 0.0938 |
| Group 3 (NP4) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.0918 μg/g | Standard Deviation 0.0738 |
| Group 4 (NP8) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.171 μg/g | Standard Deviation 0.0902 |
| Group 4 (NP8) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.103 μg/g | Standard Deviation 0.0685 |
| Group 4 (NP8) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0674 μg/g | Standard Deviation 0.038 |
| Group 5 (NT) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0833 μg/g | Standard Deviation 0.0431 |
| Group 5 (NT) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.191 μg/g | Standard Deviation 0.0895 |
| Group 5 (NT) | 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.107 μg/g | Standard Deviation 0.0818 |
p-value: <0.000195% CI: [40.4, 67.1]ANCOVA
p-value: <0.000195% CI: [39, 62.2]ANCOVA
p-value: <0.000195% CI: [32, 52.1]ANCOVA
p-value: <0.000195% CI: [35.7, 59.2]ANCOVA
p-value: 0.581795% CI: [86.8, 148]ANCOVA
p-value: 0.885295% CI: [83.7, 138]ANCOVA
p-value: 0.60795% CI: [68.7, 115]ANCOVA
Secondary
1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 1-hydroxypyrene (1-OH-Pyr) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.208 μg/g | Standard Deviation 0.147 |
| Group 1 (CC) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.00991 μg/g | Standard Deviation 0.102 |
| Group 1 (CC) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.198 μg/g | Standard Deviation 0.146 |
| Group 2 (NP2) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0489 μg/g | Standard Deviation 0.0485 |
| Group 2 (NP2) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.148 μg/g | Standard Deviation 0.102 |
| Group 2 (NP2) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.0989 μg/g | Standard Deviation 0.0704 |
| Group 3 (NP4) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0485 μg/g | Standard Deviation 0.0369 |
| Group 3 (NP4) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.145 μg/g | Standard Deviation 0.0912 |
| Group 3 (NP4) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.0969 μg/g | Standard Deviation 0.0817 |
| Group 4 (NP8) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.174 μg/g | Standard Deviation 0.114 |
| Group 4 (NP8) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.123 μg/g | Standard Deviation 0.0822 |
| Group 4 (NP8) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0506 μg/g | Standard Deviation 0.0372 |
| Group 5 (NT) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0509 μg/g | Standard Deviation 0.0325 |
| Group 5 (NT) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 0.174 μg/g | Standard Deviation 0.115 |
| Group 5 (NT) | 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.123 μg/g | Standard Deviation 0.0935 |
p-value: <0.000195% CI: [18.7, 53.9]ANCOVA
p-value: <0.000195% CI: [17.6, 46.2]ANCOVA
p-value: <0.000195% CI: [14.7, 40.2]ANCOVA
p-value: <0.000195% CI: [16.6, 47.7]ANCOVA
p-value: 0.951195% CI: [64.7, 197]ANCOVA
p-value: 195% CI: [60.4, 170]ANCOVA
p-value: 0.900395% CI: [50.6, 148]ANCOVA
Secondary
2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-aminonaphthalene (2-AN) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 21.7 ng/g | Standard Deviation 11.5 |
| Group 1 (CC) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.58 ng/g | Standard Deviation 5.1 |
| Group 1 (CC) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 20.2 ng/g | Standard Deviation 11.3 |
| Group 2 (NP2) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.07 ng/g | Standard Deviation 0.728 |
| Group 2 (NP2) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 17.0 ng/g | Standard Deviation 9.93 |
| Group 2 (NP2) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -16.0 ng/g | Standard Deviation 9.77 |
| Group 3 (NP4) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.82 ng/g | Standard Deviation 1.36 |
| Group 3 (NP4) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 21.6 ng/g | Standard Deviation 12 |
| Group 3 (NP4) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -19.8 ng/g | Standard Deviation 11.8 |
| Group 4 (NP8) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 19.8 ng/g | Standard Deviation 11.2 |
| Group 4 (NP8) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -18.3 ng/g | Standard Deviation 10.9 |
| Group 4 (NP8) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.45 ng/g | Standard Deviation 1.35 |
| Group 5 (NT) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.29 ng/g | Standard Deviation 1.01 |
| Group 5 (NT) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 20.6 ng/g | Standard Deviation 11.7 |
| Group 5 (NT) | 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -19.3 ng/g | Standard Deviation 11.7 |
p-value: <0.000195% CI: [3.29, 9.87]ANCOVA
p-value: <0.000195% CI: [4.88, 13.4]ANCOVA
p-value: <0.000195% CI: [3.88, 11.2]ANCOVA
p-value: <0.000195% CI: [3.46, 10.5]ANCOVA
p-value: 0.997295% CI: [52.7, 169]ANCOVA
p-value: 0.465595% CI: [77.9, 230]ANCOVA
p-value: 0.985195% CI: [62.1, 192]ANCOVA
Secondary
2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-hydroxypropylmercapturic acid (2-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 52.7 μg/g | Standard Deviation 28.7 |
| Group 1 (CC) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.81 μg/g | Standard Deviation 13.8 |
| Group 1 (CC) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 50.9 μg/g | Standard Deviation 31.8 |
| Group 2 (NP2) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 9.44 μg/g | Standard Deviation 3.87 |
| Group 2 (NP2) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 39.2 μg/g | Standard Deviation 19.4 |
| Group 2 (NP2) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -29.8 μg/g | Standard Deviation 20.4 |
| Group 3 (NP4) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 11.9 μg/g | Standard Deviation 3.97 |
| Group 3 (NP4) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 47.3 μg/g | Standard Deviation 28.4 |
| Group 3 (NP4) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -35.4 μg/g | Standard Deviation 26.9 |
| Group 4 (NP8) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 45.4 μg/g | Standard Deviation 23.8 |
| Group 4 (NP8) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -33.0 μg/g | Standard Deviation 26 |
| Group 4 (NP8) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 12.5 μg/g | Standard Deviation 7.43 |
| Group 5 (NT) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 11.9 μg/g | Standard Deviation 3.97 |
| Group 5 (NT) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 41.4 μg/g | Standard Deviation 23.6 |
| Group 5 (NT) | 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -29.6 μg/g | Standard Deviation 22.4 |
p-value: <0.000195% CI: [17, 30.4]ANCOVA
p-value: <0.000195% CI: [21.6, 36.6]ANCOVA
p-value: <0.000195% CI: [20.8, 36.2]ANCOVA
p-value: <0.000195% CI: [21.4, 38.4]ANCOVA
p-value: 0.184395% CI: [58.6, 108]ANCOVA
p-value: 0.999495% CI: [73.9, 130]ANCOVA
p-value: 0.989195% CI: [71.4, 129]ANCOVA
Secondary
2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-hydroxybutenylmercapturic acid (2-MHBMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.93 μg/g | Standard Deviation 1.53 |
| Group 1 (CC) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.194 μg/g | Standard Deviation 0.517 |
| Group 1 (CC) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.74 μg/g | Standard Deviation 1.33 |
| Group 2 (NP2) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0359 μg/g | Standard Deviation 0.0338 |
| Group 2 (NP2) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.24 μg/g | Standard Deviation 1.12 |
| Group 2 (NP2) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.20 μg/g | Standard Deviation 1.11 |
| Group 3 (NP4) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0487 μg/g | Standard Deviation 0.0466 |
| Group 3 (NP4) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.60 μg/g | Standard Deviation 1.66 |
| Group 3 (NP4) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.56 μg/g | Standard Deviation 1.63 |
| Group 4 (NP8) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.47 μg/g | Standard Deviation 1.37 |
| Group 4 (NP8) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.43 μg/g | Standard Deviation 1.36 |
| Group 4 (NP8) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0460 μg/g | Standard Deviation 0.0413 |
| Group 5 (NT) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.0729 μg/g | Standard Deviation 0.08 |
| Group 5 (NT) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.26 μg/g | Standard Deviation 1.15 |
| Group 5 (NT) | 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.19 μg/g | Standard Deviation 1.11 |
p-value: <0.000195% CI: [1.88, 7.31]ANCOVA
p-value: <0.000195% CI: [2.28, 7.93]ANCOVA
p-value: <0.000195% CI: [2.2, 8.14]ANCOVA
p-value: <0.000195% CI: [3.22, 12.7]ANCOVA
p-value: 0.18495% CI: [28.3, 119]ANCOVA
p-value: 0.355295% CI: [34, 130]ANCOVA
p-value: 0.38195% CI: [33, 133]ANCOVA
Secondary
2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-OH-Fluorene (2-OH-Flu) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 2.24 μg/g | Standard Deviation 1.11 |
| Group 1 (CC) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.159 μg/g | Standard Deviation 0.401 |
| Group 1 (CC) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 2.08 μg/g | Standard Deviation 1.17 |
| Group 2 (NP2) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.280 μg/g | Standard Deviation 0.144 |
| Group 2 (NP2) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1.71 μg/g | Standard Deviation 0.89 |
| Group 2 (NP2) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.43 μg/g | Standard Deviation 0.777 |
| Group 3 (NP4) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.356 μg/g | Standard Deviation 0.141 |
| Group 3 (NP4) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 2.01 μg/g | Standard Deviation 1.08 |
| Group 3 (NP4) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.65 μg/g | Standard Deviation 0.995 |
| Group 4 (NP8) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 2.14 μg/g | Standard Deviation 1.09 |
| Group 4 (NP8) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.78 μg/g | Standard Deviation 0.916 |
| Group 4 (NP8) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.361 μg/g | Standard Deviation 0.225 |
| Group 5 (NT) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.345 μg/g | Standard Deviation 0.203 |
| Group 5 (NT) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 2.08 μg/g | Standard Deviation 1.11 |
| Group 5 (NT) | 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.73 μg/g | Standard Deviation 0.931 |
p-value: <0.000195% CI: [13, 21.8]ANCOVA
p-value: <0.000195% CI: [16.2, 25.9]ANCOVA
p-value: <0.000195% CI: [14.3, 23.4]ANCOVA
p-value: <0.000195% CI: [13.7, 23.1]ANCOVA
p-value: 0.958995% CI: [72, 124]ANCOVA
p-value: 0.444295% CI: [89.3, 148]ANCOVA
p-value: 0.997595% CI: [78.8, 133]ANCOVA
Secondary
2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-Naphthol (2-OH-Nap) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.1 μg/g | Standard Deviation 5.08 |
| Group 1 (CC) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.550 μg/g | Standard Deviation 2.55 |
| Group 1 (CC) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 10.6 μg/g | Standard Deviation 5.06 |
| Group 2 (NP2) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 5.16 μg/g | Standard Deviation 6.38 |
| Group 2 (NP2) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.5 μg/g | Standard Deviation 8.46 |
| Group 2 (NP2) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.38 μg/g | Standard Deviation 3.86 |
| Group 3 (NP4) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 5.26 μg/g | Standard Deviation 3.89 |
| Group 3 (NP4) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 12.6 μg/g | Standard Deviation 5.56 |
| Group 3 (NP4) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -7.31 μg/g | Standard Deviation 5.2 |
| Group 4 (NP8) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 13.8 μg/g | Standard Deviation 7.01 |
| Group 4 (NP8) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -9.00 μg/g | Standard Deviation 5.09 |
| Group 4 (NP8) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.80 μg/g | Standard Deviation 4.38 |
| Group 5 (NT) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 6.00 μg/g | Standard Deviation 5.56 |
| Group 5 (NT) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.8 μg/g | Standard Deviation 7.6 |
| Group 5 (NT) | 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -5.81 μg/g | Standard Deviation 5.91 |
p-value: <0.000195% CI: [23.9, 55.6]ANCOVA
p-value: <0.000195% CI: [27.1, 59]ANCOVA
p-value: <0.000195% CI: [20.1, 45.5]ANCOVA
p-value: 0.000295% CI: [31.9, 75]ANCOVA
p-value: 0.293895% CI: [47.6, 117]ANCOVA
p-value: 0.555295% CI: [53.7, 124]ANCOVA
p-value: 0.025495% CI: [39.9, 95.5]ANCOVA
Secondary
3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 3-hydroxypropylmercapturic acid (3-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1250 μg/g | Standard Deviation 605 |
| Group 1 (CC) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -82.7 μg/g | Standard Deviation 299 |
| Group 1 (CC) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1170 μg/g | Standard Deviation 614 |
| Group 2 (NP2) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 195 μg/g | Standard Deviation 98.9 |
| Group 2 (NP2) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 969 μg/g | Standard Deviation 414 |
| Group 2 (NP2) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -774 μg/g | Standard Deviation 410 |
| Group 3 (NP4) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 259 μg/g | Standard Deviation 118 |
| Group 3 (NP4) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1160 μg/g | Standard Deviation 550 |
| Group 3 (NP4) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -897 μg/g | Standard Deviation 557 |
| Group 4 (NP8) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1170 μg/g | Standard Deviation 516 |
| Group 4 (NP8) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -957 μg/g | Standard Deviation 494 |
| Group 4 (NP8) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 215 μg/g | Standard Deviation 98.7 |
| Group 5 (NT) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 281 μg/g | Standard Deviation 205 |
| Group 5 (NT) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 1200 μg/g | Standard Deviation 844 |
| Group 5 (NT) | 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -923 μg/g | Standard Deviation 836 |
p-value: <0.000195% CI: [13.2, 25.3]ANCOVA
p-value: <0.000195% CI: [17.6, 31.9]ANCOVA
p-value: <0.000195% CI: [14.2, 26.4]ANCOVA
p-value: <0.000195% CI: [17.3, 33.3]ANCOVA
p-value: 0.15395% CI: [54, 107]ANCOVA
p-value: 0.999995% CI: [71.7, 136]ANCOVA
p-value: 0.302595% CI: [57.8, 112]ANCOVA
Secondary
3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 3-hydroxybenzo\[a\]pyrene (3-OH-B\[a\]P) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 216 pg/g | Standard Deviation 155 |
| Group 1 (CC) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | 30.0 pg/g | Standard Deviation 192 |
| Group 1 (CC) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 246 pg/g | Standard Deviation 215 |
| Group 2 (NP2) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 30.8 pg/g | Standard Deviation 50.9 |
| Group 2 (NP2) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 139 pg/g | Standard Deviation 111 |
| Group 2 (NP2) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -108 pg/g | Standard Deviation 109 |
| Group 3 (NP4) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 82.5 pg/g | Standard Deviation 105 |
| Group 3 (NP4) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 223 pg/g | Standard Deviation 158 |
| Group 3 (NP4) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -141 pg/g | Standard Deviation 186 |
| Group 4 (NP8) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 172 pg/g | Standard Deviation 139 |
| Group 4 (NP8) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -115 pg/g | Standard Deviation 160 |
| Group 4 (NP8) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 57.7 pg/g | Standard Deviation 77.6 |
| Group 5 (NT) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 84.8 pg/g | Standard Deviation 174 |
| Group 5 (NT) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 166 pg/g | Standard Deviation 101 |
| Group 5 (NT) | 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -80.8 pg/g | Standard Deviation 195 |
p-value: <0.000195% CI: [5.44, 32]ANCOVA
p-value: <0.000195% CI: [10.7, 53.3]ANCOVA
p-value: 0.000395% CI: [10.6, 57.4]ANCOVA
p-value: 0.000295% CI: [9.21, 54.1]ANCOVA
p-value: 0.42895% CI: [23.3, 150]ANCOVA
p-value: 0.99995% CI: [44.8, 255]ANCOVA
p-value: 0.995895% CI: [44.9, 272]ANCOVA
Secondary
4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 4-aminobiphenyl (4-ABP) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 13.8 ng/g | Standard Deviation 6.74 |
| Group 1 (CC) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.589 ng/g | Standard Deviation 4.53 |
| Group 1 (CC) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 13.2 ng/g | Standard Deviation 7.44 |
| Group 2 (NP2) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.42 ng/g | Standard Deviation 0.45 |
| Group 2 (NP2) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 10.2 ng/g | Standard Deviation 5.04 |
| Group 2 (NP2) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -8.75 ng/g | Standard Deviation 4.94 |
| Group 3 (NP4) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.97 ng/g | Standard Deviation 0.749 |
| Group 3 (NP4) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 13.3 ng/g | Standard Deviation 6.29 |
| Group 3 (NP4) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -11.3 ng/g | Standard Deviation 6.04 |
| Group 4 (NP8) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 12.8 ng/g | Standard Deviation 6.22 |
| Group 4 (NP8) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -11.1 ng/g | Standard Deviation 5.81 |
| Group 4 (NP8) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.72 ng/g | Standard Deviation 0.985 |
| Group 5 (NT) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.92 ng/g | Standard Deviation 1.04 |
| Group 5 (NT) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 12.8 ng/g | Standard Deviation 6.81 |
| Group 5 (NT) | 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -10.9 ng/g | Standard Deviation 6.58 |
p-value: <0.000195% CI: [9.72, 19.2]ANCOVA
p-value: <0.000195% CI: [12.1, 22.6]ANCOVA
p-value: <0.000195% CI: [9.68, 18.6]ANCOVA
p-value: <0.000195% CI: [11.2, 22.2]ANCOVA
p-value: 0.716795% CI: [60.6, 124]ANCOVA
p-value: 0.986495% CI: [75.3, 147]ANCOVA
p-value: 0.591195% CI: [60.1, 120]ANCOVA
Secondary
AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoylethyl) cysteine (AAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 92.6 μg/g | Standard Deviation 30.5 |
| Group 1 (CC) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -4.90 μg/g | Standard Deviation 19 |
| Group 1 (CC) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 87.7 μg/g | Standard Deviation 31.8 |
| Group 2 (NP2) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 29.4 μg/g | Standard Deviation 6.96 |
| Group 2 (NP2) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 82.6 μg/g | Standard Deviation 36.1 |
| Group 2 (NP2) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -53.1 μg/g | Standard Deviation 33 |
| Group 3 (NP4) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 39.1 μg/g | Standard Deviation 12.7 |
| Group 3 (NP4) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 95.6 μg/g | Standard Deviation 29.7 |
| Group 3 (NP4) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -56.5 μg/g | Standard Deviation 27 |
| Group 4 (NP8) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 94.0 μg/g | Standard Deviation 36.4 |
| Group 4 (NP8) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -57.3 μg/g | Standard Deviation 32.1 |
| Group 4 (NP8) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 36.7 μg/g | Standard Deviation 13.4 |
| Group 5 (NT) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 35.9 μg/g | Standard Deviation 10.4 |
| Group 5 (NT) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 94.3 μg/g | Standard Deviation 46 |
| Group 5 (NT) | AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -58.3 μg/g | Standard Deviation 43.1 |
p-value: <0.000195% CI: [30.4, 45.7]ANCOVA
p-value: <0.000195% CI: [36.5, 53.1]ANCOVA
p-value: <0.000195% CI: [34.4, 50.9]ANCOVA
p-value: <0.000195% CI: [34.9, 52.7]ANCOVA
p-value: 0.302795% CI: [70, 108]ANCOVA
p-value: 0.992695% CI: [83.9, 125]ANCOVA
p-value: 0.993895% CI: [79.1, 120]ANCOVA
Secondary
Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of blood carboxyhemoglobin (%) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. The absolute change from baseline of urine biomarker amount excreted in 24 hours and blood biomarker concentration will be calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value where Baseline = Day -1
Time frame: Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.8 percent saturation | Standard Deviation 4.2 |
| Group 1 (CC) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.585 percent saturation | Standard Deviation 4 |
| Group 1 (CC) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 11.3 percent saturation | Standard Deviation 4.29 |
| Group 2 (NP2) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.99 percent saturation | Standard Deviation 1.67 |
| Group 2 (NP2) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 10.3 percent saturation | Standard Deviation 3.59 |
| Group 2 (NP2) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -5.35 percent saturation | Standard Deviation 4.01 |
| Group 3 (NP4) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.60 percent saturation | Standard Deviation 1.14 |
| Group 3 (NP4) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.3 percent saturation | Standard Deviation 3.2 |
| Group 3 (NP4) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.65 percent saturation | Standard Deviation 3.28 |
| Group 4 (NP8) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.1 percent saturation | Standard Deviation 5.25 |
| Group 4 (NP8) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.49 percent saturation | Standard Deviation 5.12 |
| Group 4 (NP8) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.60 percent saturation | Standard Deviation 0.918 |
| Group 5 (NT) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.22 percent saturation | Standard Deviation 1.02 |
| Group 5 (NT) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.0 percent saturation | Standard Deviation 3.84 |
| Group 5 (NT) | Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.77 percent saturation | Standard Deviation 3.5 |
p-value: <0.000195% CI: [37.1, 58]ANCOVA
p-value: <0.000195% CI: [35.1, 52.9]ANCOVA
p-value: <0.000195% CI: [35.5, 54.6]ANCOVA
p-value: <0.000195% CI: [31, 49.4]ANCOVA
p-value: 0.235195% CI: [93.2, 151]ANCOVA
p-value: 0.65795% CI: [87.7, 138]ANCOVA
p-value: 0.511295% CI: [89.1, 142]ANCOVA
Secondary
CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted cyanoethylmercapturic acid (CEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 163 μg/g | Standard Deviation 74.1 |
| Group 1 (CC) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -12.4 μg/g | Standard Deviation 28.9 |
| Group 1 (CC) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 150 μg/g | Standard Deviation 72.1 |
| Group 2 (NP2) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 17.4 μg/g | Standard Deviation 10.3 |
| Group 2 (NP2) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 133 μg/g | Standard Deviation 65 |
| Group 2 (NP2) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -116 μg/g | Standard Deviation 56.6 |
| Group 3 (NP4) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 18.9 μg/g | Standard Deviation 10.7 |
| Group 3 (NP4) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 154 μg/g | Standard Deviation 83.4 |
| Group 3 (NP4) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -135 μg/g | Standard Deviation 75.8 |
| Group 4 (NP8) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 170 μg/g | Standard Deviation 72.9 |
| Group 4 (NP8) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -147 μg/g | Standard Deviation 67.5 |
| Group 4 (NP8) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 23.0 μg/g | Standard Deviation 13.1 |
| Group 5 (NT) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 16.0 μg/g | Standard Deviation 11.6 |
| Group 5 (NT) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 160 μg/g | Standard Deviation 94.8 |
| Group 5 (NT) | CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -144 μg/g | Standard Deviation 85.4 |
p-value: <0.000195% CI: [9.57, 18.4]ANCOVA
p-value: <0.000195% CI: [9.84, 17.9]ANCOVA
p-value: <0.000195% CI: [9.93, 18.6]ANCOVA
p-value: <0.000195% CI: [6.67, 12.9]ANCOVA
p-value: 0.040495% CI: [101, 202]ANCOVA
p-value: 0.024395% CI: [104, 198]ANCOVA
p-value: 0.021595% CI: [105, 205]ANCOVA
Secondary
GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-1-cysteine (GAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 14.4 μg/g | Standard Deviation 6.15 |
| Group 1 (CC) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.256 μg/g | Standard Deviation 3.59 |
| Group 1 (CC) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 14.1 μg/g | Standard Deviation 6.48 |
| Group 2 (NP2) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 5.93 μg/g | Standard Deviation 1.94 |
| Group 2 (NP2) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 13.1 μg/g | Standard Deviation 5.27 |
| Group 2 (NP2) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -7.20 μg/g | Standard Deviation 3.99 |
| Group 3 (NP4) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 7.58 μg/g | Standard Deviation 1.88 |
| Group 3 (NP4) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 14.3 μg/g | Standard Deviation 4.29 |
| Group 3 (NP4) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.77 μg/g | Standard Deviation 3.51 |
| Group 4 (NP8) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 14.7 μg/g | Standard Deviation 5.23 |
| Group 4 (NP8) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -7.35 μg/g | Standard Deviation 4.11 |
| Group 4 (NP8) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 7.30 μg/g | Standard Deviation 2.24 |
| Group 5 (NT) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 7.26 μg/g | Standard Deviation 2.26 |
| Group 5 (NT) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 14.1 μg/g | Standard Deviation 5.89 |
| Group 5 (NT) | GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6.79 μg/g | Standard Deviation 4.94 |
p-value: <0.000195% CI: [39.5, 54.4]ANCOVA
p-value: <0.000195% CI: [48, 64.4]ANCOVA
p-value: <0.000195% CI: [45.2, 61.5]ANCOVA
p-value: <0.000195% CI: [46.7, 64.5]ANCOVA
p-value: 0.050495% CI: [71.2, 100]ANCOVA
p-value: 0.998895% CI: [86.4, 119]ANCOVA
p-value: 0.923895% CI: [81.4, 113]ANCOVA
Secondary
HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 2-hydroxyethylmercapturic acid (HEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 5.19 μg/g | Standard Deviation 5.34 |
| Group 1 (CC) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.559 μg/g | Standard Deviation 1.8 |
| Group 1 (CC) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.63 μg/g | Standard Deviation 4.47 |
| Group 2 (NP2) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.959 μg/g | Standard Deviation 0.66 |
| Group 2 (NP2) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 2.98 μg/g | Standard Deviation 1.69 |
| Group 2 (NP2) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -2.03 μg/g | Standard Deviation 1.4 |
| Group 3 (NP4) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.18 μg/g | Standard Deviation 0.758 |
| Group 3 (NP4) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 5.64 μg/g | Standard Deviation 5.29 |
| Group 3 (NP4) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -4.46 μg/g | Standard Deviation 4.63 |
| Group 4 (NP8) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 5.65 μg/g | Standard Deviation 6.11 |
| Group 4 (NP8) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -4.09 μg/g | Standard Deviation 5.5 |
| Group 4 (NP8) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.55 μg/g | Standard Deviation 1.11 |
| Group 5 (NT) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1.30 μg/g | Standard Deviation 0.762 |
| Group 5 (NT) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 3.90 μg/g | Standard Deviation 3.42 |
| Group 5 (NT) | HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -2.60 μg/g | Standard Deviation 3.22 |
p-value: <0.000195% CI: [21.8, 40]ANCOVA
p-value: <0.000195% CI: [21.5, 37.4]ANCOVA
p-value: <0.000195% CI: [24.8, 44.2]ANCOVA
p-value: <0.000195% CI: [27.7, 50.9]ANCOVA
p-value: 0.19595% CI: [57.3, 108]ANCOVA
p-value: 0.069995% CI: [56.1, 102]ANCOVA
p-value: 0.704195% CI: [64.7, 120]ANCOVA
Secondary
HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 371 μg/g | Standard Deviation 161 |
| Group 1 (CC) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -25.6 μg/g | Standard Deviation 75.6 |
| Group 1 (CC) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 345 μg/g | Standard Deviation 159 |
| Group 2 (NP2) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 53.4 μg/g | Standard Deviation 10.4 |
| Group 2 (NP2) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 303 μg/g | Standard Deviation 121 |
| Group 2 (NP2) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -250 μg/g | Standard Deviation 120 |
| Group 3 (NP4) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 57.1 μg/g | Standard Deviation 25 |
| Group 3 (NP4) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 325 μg/g | Standard Deviation 167 |
| Group 3 (NP4) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -268 μg/g | Standard Deviation 163 |
| Group 4 (NP8) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 338 μg/g | Standard Deviation 143 |
| Group 4 (NP8) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -290 μg/g | Standard Deviation 142 |
| Group 4 (NP8) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 48.6 μg/g | Standard Deviation 10.3 |
| Group 5 (NT) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 55.2 μg/g | Standard Deviation 12.4 |
| Group 5 (NT) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 353 μg/g | Standard Deviation 198 |
| Group 5 (NT) | HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -298 μg/g | Standard Deviation 197 |
p-value: <0.000195% CI: [14.4, 22.3]ANCOVA
p-value: <0.000195% CI: [14.8, 22.1]ANCOVA
p-value: <0.000195% CI: [12.8, 19.4]ANCOVA
p-value: <0.000195% CI: [14.6, 22.7]ANCOVA
p-value: 0.999395% CI: [78.2, 124]ANCOVA
p-value: 0.999895% CI: [79.7, 123]ANCOVA
p-value: 0.301995% CI: [69.1, 108]ANCOVA
Secondary
NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted Nicotine Equivalents (NE) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during the 24 hours was converted to 24-hour urine volume using the assumed density of 1 gram (g) equals 1 milliliter (mL). The amount of biomarker was calculated as follows: NE concentration (μg/mL) = (nicotine \[ng/mL\]/162.23 \[mg/mmol\] + nicotine-gluc \[ng/mL\]/338.36 \[mg/mmol\] + cotinine \[ng/mL\]/176.22 \[mg/mmol\] + cotinine-gluc \[ng/mL\]/352.34 \[mg/mmol\] + trans-3'-hydroxycotinine \[ng/mL\]/192.22 \[mg/mmol\] + trans-3'-hydroxycotinine-gluc \[ng/mL\]/368.34 \[mg/mmol\]) × 162.23 (mg/mmol) × 1 μg/1000 ng Adjusted Nicotine equivalents (mg NE/g creatinine) = NE concentration (μg/mL) × 100 / Creatinine concentration (mg/dL) Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 11.6 mg/g | Standard Deviation 6.55 |
| Group 1 (CC) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.20 mg/g | Standard Deviation 3.81 |
| Group 1 (CC) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 10.4 mg/g | Standard Deviation 5.1 |
| Group 2 (NP2) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 5.79 mg/g | Standard Deviation 5.01 |
| Group 2 (NP2) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 8.73 mg/g | Standard Deviation 4.42 |
| Group 2 (NP2) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -2.94 mg/g | Standard Deviation 3.8 |
| Group 3 (NP4) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 8.80 mg/g | Standard Deviation 6.66 |
| Group 3 (NP4) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 10.3 mg/g | Standard Deviation 4.83 |
| Group 3 (NP4) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -1.50 mg/g | Standard Deviation 5.81 |
| Group 4 (NP8) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 10.5 mg/g | Standard Deviation 5.99 |
| Group 4 (NP8) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | 1.34 mg/g | Standard Deviation 6.77 |
| Group 4 (NP8) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 11.8 mg/g | Standard Deviation 8.45 |
| Group 5 (NT) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.978 mg/g | Standard Deviation 2.35 |
| Group 5 (NT) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 12.2 mg/g | Standard Deviation 7.34 |
| Group 5 (NT) | NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -11.2 mg/g | Standard Deviation 6.89 |
p-value: 0.099495% CI: [22.7, 110]ANCOVA
p-value: 0.416295% CI: [32, 135]ANCOVA
p-value: 195% CI: [47.5, 215]ANCOVA
p-value: <0.000195% CI: [1.01, 4.94]ANCOVA
p-value: <0.000195% CI: [965, 5160]ANCOVA
p-value: <0.000195% CI: [1350, 6400]ANCOVA
p-value: <0.000195% CI: [2020, 10200]ANCOVA
Secondary
SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urinary creatinine-adjusted S-phenylmercapturic acid (SPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 4.41 μg/g | Standard Deviation 3.29 |
| Group 1 (CC) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -0.265 μg/g | Standard Deviation 0.81 |
| Group 1 (CC) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 4.14 μg/g | Standard Deviation 3.24 |
| Group 2 (NP2) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.149 μg/g | Standard Deviation 0.108 |
| Group 2 (NP2) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 3.03 μg/g | Standard Deviation 2.24 |
| Group 2 (NP2) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -2.88 μg/g | Standard Deviation 2.17 |
| Group 3 (NP4) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.183 μg/g | Standard Deviation 0.106 |
| Group 3 (NP4) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 3.90 μg/g | Standard Deviation 2.41 |
| Group 3 (NP4) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -3.72 μg/g | Standard Deviation 2.38 |
| Group 4 (NP8) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 3.79 μg/g | Standard Deviation 2.7 |
| Group 4 (NP8) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -3.61 μg/g | Standard Deviation 2.67 |
| Group 4 (NP8) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.186 μg/g | Standard Deviation 0.14 |
| Group 5 (NT) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 0.171 μg/g | Standard Deviation 0.107 |
| Group 5 (NT) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 3.54 μg/g | Standard Deviation 3.18 |
| Group 5 (NT) | SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -3.37 μg/g | Standard Deviation 3.09 |
p-value: <0.000195% CI: [3.69, 7.8]ANCOVA
p-value: <0.000195% CI: [4.01, 7.96]ANCOVA
p-value: <0.000195% CI: [3.92, 8.03]ANCOVA
p-value: <0.000195% CI: [4.17, 8.89]ANCOVA
p-value: 0.833595% CI: [59.4, 131]ANCOVA
p-value: 0.962295% CI: [64.2, 134]ANCOVA
p-value: 0.953195% CI: [62.8, 135]ANCOVA
Secondary
Summary of Average Duration of Each Nicotine Pouch Use
The average duration (in minutes) of each nicotine pouch use from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.
Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Population: The Product Use Population includes all subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. Only subjects in NP2, NP4 and NP8 groups used nicotine pouch products during the study and data from only these subjects are provided in the summary for average duration of each nicotine pouch use.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 2 | 25.1 minutes | Standard Deviation 11.8 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 5 | 27.4 minutes | Standard Deviation 14.2 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 4 | 27.6 minutes | Standard Deviation 15.1 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 1 | 23.5 minutes | Standard Deviation 13.3 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 7 | 25.5 minutes | Standard Deviation 13 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 6 | 30.1 minutes | Standard Deviation 13.8 |
| Group 1 (CC) | Summary of Average Duration of Each Nicotine Pouch Use | Day 3 | 27.6 minutes | Standard Deviation 13.4 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 4 | 25.4 minutes | Standard Deviation 11 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 1 | 22.4 minutes | Standard Deviation 10.3 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 2 | 25.1 minutes | Standard Deviation 13.2 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 3 | 25.5 minutes | Standard Deviation 14.5 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 5 | 27.3 minutes | Standard Deviation 13.2 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 6 | 26.0 minutes | Standard Deviation 13.1 |
| Group 2 (NP2) | Summary of Average Duration of Each Nicotine Pouch Use | Day 7 | 24.5 minutes | Standard Deviation 12.4 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 5 | 26.8 minutes | Standard Deviation 18.8 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 2 | 21.6 minutes | Standard Deviation 13.6 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 7 | 27.3 minutes | Standard Deviation 19.7 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 6 | 28.9 minutes | Standard Deviation 20.2 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 4 | 26.2 minutes | Standard Deviation 18.5 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 3 | 23.3 minutes | Standard Deviation 13.5 |
| Group 3 (NP4) | Summary of Average Duration of Each Nicotine Pouch Use | Day 1 | 19.1 minutes | Standard Deviation 11.4 |
Secondary
Summary of Average Number of Nicotine Pouches Per Use
The average number of nicotine pouches per use occasion (NPPU) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.
Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Population: The Product Use Population includes all subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. Only subjects in NP2, NP4 and NP8 groups used nicotine pouch products during the study and data from only these subjects are provided in the NPPU summary.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 4 | 1.25 nicotine pouches per use | Standard Deviation 0.436 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 7 | 1.37 nicotine pouches per use | Standard Deviation 0.513 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 3 | 1.26 nicotine pouches per use | Standard Deviation 0.468 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 6 | 1.35 nicotine pouches per use | Standard Deviation 0.461 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 1 | 1.19 nicotine pouches per use | Standard Deviation 0.309 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 5 | 1.26 nicotine pouches per use | Standard Deviation 0.42 |
| Group 1 (CC) | Summary of Average Number of Nicotine Pouches Per Use | Day 2 | 1.22 nicotine pouches per use | Standard Deviation 0.434 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 5 | 1.33 nicotine pouches per use | Standard Deviation 0.419 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 6 | 1.35 nicotine pouches per use | Standard Deviation 0.481 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 7 | 1.38 nicotine pouches per use | Standard Deviation 0.473 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 2 | 1.28 nicotine pouches per use | Standard Deviation 0.404 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 4 | 1.32 nicotine pouches per use | Standard Deviation 0.389 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 3 | 1.33 nicotine pouches per use | Standard Deviation 0.575 |
| Group 2 (NP2) | Summary of Average Number of Nicotine Pouches Per Use | Day 1 | 1.22 nicotine pouches per use | Standard Deviation 0.285 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 7 | 1.13 nicotine pouches per use | Standard Deviation 0.227 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 1 | 1.09 nicotine pouches per use | Standard Deviation 0.204 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 2 | 1.15 nicotine pouches per use | Standard Deviation 0.378 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 4 | 1.18 nicotine pouches per use | Standard Deviation 0.308 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 5 | 1.13 nicotine pouches per use | Standard Deviation 0.255 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 6 | 1.13 nicotine pouches per use | Standard Deviation 0.256 |
| Group 3 (NP4) | Summary of Average Number of Nicotine Pouches Per Use | Day 3 | 1.21 nicotine pouches per use | Standard Deviation 0.444 |
Secondary
Summary of Cigarettes Smoked Per Day (CPD)
The number of cigarettes smoked per day (CPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Subjects in NP2, NP4, NP8 and NT groups were not allowed to use cigarettes starting at Day 1.
Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Population: The Product Use Population includes all subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. Only subjects in the CC group were permitted to continue smoking their own brand of cigarettes and only data for these subjects is presented in the CPD summary.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 1 | 16.1 cigarettes per day | Standard Deviation 5.91 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 2 | 15.8 cigarettes per day | Standard Deviation 6.11 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 3 | 15.6 cigarettes per day | Standard Deviation 6.26 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 4 | 14.8 cigarettes per day | Standard Deviation 7.25 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 5 | 15.8 cigarettes per day | Standard Deviation 6.79 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 6 | 15.8 cigarettes per day | Standard Deviation 7.56 |
| Group 1 (CC) | Summary of Cigarettes Smoked Per Day (CPD) | Day 7 | 15.9 cigarettes per day | Standard Deviation 7.18 |
Secondary
Summary of Total Number of Nicotine Pouches Used Per Day (NPPD)
The number of nicotine pouches used per day (NPPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.
Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Population: The Product Use Population includes all subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. Only subjects in NP2, NP4 and NP8 groups used nicotine pouch products during the study and data from only these subjects are provided in the NPPD summary.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 2 | 9.22 nicotine pouches per day | Standard Deviation 6.16 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 5 | 10.1 nicotine pouches per day | Standard Deviation 6.82 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 4 | 9.48 nicotine pouches per day | Standard Deviation 6.46 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 1 | 9.78 nicotine pouches per day | Standard Deviation 6 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 7 | 10.8 nicotine pouches per day | Standard Deviation 7.77 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 6 | 10.7 nicotine pouches per day | Standard Deviation 6.34 |
| Group 1 (CC) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 3 | 10.5 nicotine pouches per day | Standard Deviation 7.12 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 4 | 10.2 nicotine pouches per day | Standard Deviation 6.25 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 1 | 9.77 nicotine pouches per day | Standard Deviation 5.64 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 2 | 10.2 nicotine pouches per day | Standard Deviation 5.47 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 3 | 9.87 nicotine pouches per day | Standard Deviation 5.53 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 5 | 10.4 nicotine pouches per day | Standard Deviation 5.7 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 6 | 10.1 nicotine pouches per day | Standard Deviation 5.71 |
| Group 2 (NP2) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 7 | 11.2 nicotine pouches per day | Standard Deviation 6.91 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 5 | 7.36 nicotine pouches per day | Standard Deviation 4.24 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 2 | 6.93 nicotine pouches per day | Standard Deviation 4.06 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 7 | 7.60 nicotine pouches per day | Standard Deviation 4.24 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 6 | 7.12 nicotine pouches per day | Standard Deviation 3.88 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 4 | 7.15 nicotine pouches per day | Standard Deviation 4 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 3 | 7.34 nicotine pouches per day | Standard Deviation 4.56 |
| Group 3 (NP4) | Summary of Total Number of Nicotine Pouches Used Per Day (NPPD) | Day 1 | 7.27 nicotine pouches per day | Standard Deviation 4.96 |
Secondary
Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Summary of 24-hour urine mutagenicity (Rev/24h) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. Measurement results are reported as revertants/μL. Urine mutagenicity count in the 24-hour urine was calculated as: Urine mutagenicity (revertants/250 mL) = Urine mutagenicity (revertants/μL) x 1000V, where V is the volume after concentration in mL Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x \[24h urine volume(mL) ÷ V\], where V is the volume in mL of urine sample used for the mutagenicity test
Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7
Population: Biomarker of Exposure Population (BOE): All subjects from Groups 1, 2, 3, and 4 who used at least 1 of the assigned study products and all Group 5 subjects. To be included in the BOE population, subjects must have baseline (Day -1) and at least one post-baseline evaluable BOE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (CC) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 10800 Revertants / 24 hours | Standard Deviation 13000 |
| Group 1 (CC) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 13300 Revertants / 24 hours | Standard Deviation 14000 |
| Group 1 (CC) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -2460 Revertants / 24 hours | Standard Deviation 8160 |
| Group 2 (NP2) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 8770 Revertants / 24 hours | Standard Deviation 9480 |
| Group 2 (NP2) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6980 Revertants / 24 hours | Standard Deviation 9170 |
| Group 2 (NP2) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1710 Revertants / 24 hours | Standard Deviation 3150 |
| Group 3 (NP4) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 9170 Revertants / 24 hours | Standard Deviation 11100 |
| Group 3 (NP4) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 2400 Revertants / 24 hours | Standard Deviation 3550 |
| Group 3 (NP4) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -6770 Revertants / 24 hours | Standard Deviation 11800 |
| Group 4 (NP8) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -5650 Revertants / 24 hours | Standard Deviation 7460 |
| Group 4 (NP8) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 7580 Revertants / 24 hours | Standard Deviation 8210 |
| Group 4 (NP8) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 1920 Revertants / 24 hours | Standard Deviation 2440 |
| Group 5 (NT) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day 7 | 3390 Revertants / 24 hours | Standard Deviation 5250 |
| Group 5 (NT) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Day -1 (Baseline) | 12000 Revertants / 24 hours | Standard Deviation 12700 |
| Group 5 (NT) | Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days | Change from Baseline to Day 7 | -8640 Revertants / 24 hours | Standard Deviation 9980 |
p-value: <0.000195% CI: [-77.7, -23.9]ANCOVA
p-value: <0.000195% CI: [-69.6, -20.3]ANCOVA
p-value: 0.000395% CI: [-68.2, -16.5]ANCOVA
p-value: 0.000495% CI: [-72.6, -17]ANCOVA
p-value: 0.955195% CI: [-35.2, 23.1]ANCOVA
p-value: 195% CI: [-27.3, 26.9]ANCOVA
p-value: 0.998195% CI: [-25.6, 30.6]ANCOVA