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| Name | Class |
|---|---|
| Covance | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 (CC) | No Intervention | Subjects will be asked to continue smoking their UBCs ad libitum for 7 days. | |
| Group 2 (NP2) | Experimental | Subjects will exclusively use 2 mg NP, using at least 3 pouches per day for 7 days. |
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| Group 3 (NP4) | Experimental | Subjects will exclusively use 4 mg NP, using at least 3 pouches per day for 7 days. |
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| Group 4 (NP8) | Experimental | Subjects will exclusively use 8 mg NP, using at least 3 pouches per day for 7 days. |
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| Group 5 (NT) | Experimental | Subjects will completely stop all tobacco product usage for 7 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OTDN Product 1 | Other | Mint on!® 2 mg nicotine pouches |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Voluntary consent to participate in this study documented on the signed ICF
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
Positive urine cotinine (≥ 500 ng/mL) at screening
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:
Female subjects of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.
Female subjects who are of nonchildbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to check-in:
Hysteroscopic sterilization (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
Willing to comply with the requirements of the study
Willing to use all 3 on!® NP after the Product Trial at check-in
Willing and able to abstain from cigarettes from Day 1 through the end of the study (EOS)
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:
Not more than 60% of either gender
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| Name | Affiliation | Role |
|---|---|---|
| William J Howitt, MD | QPS Holdings LLC | Principal Investigator |
| William Smith, MD | NOCCR | Principal Investigator |
| Mark Adams, MD | CKRA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CKRA | Lexington | Kentucky | 40509 | United States | ||
| QPS |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Not Assigned | Only includes 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. |
| FG001 | Group 1 (CC) | Subjects will be asked to continue smoking their UBCs ad libitum for 7 days. |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The Baseline Analysis Population includes all subjects randomized to a study group (Group 1, 2, 3, 4 or 5), and any subject who was enrolled in the study but failed to meet randomization criteria and was discontinued by the PI. Subjects who met eligibility requirements but were not needed for the study are not included in the Baseline Analysis Population.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Group 1 (CC) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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. | Posted | Mean | Standard Deviation | ng/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
Adverse events were monitored from the time the subject first signs the ICF (within 28 days prior to randomization) to final discharge from the study (up to 8 days after randomization).
Subjects were observed for any signs or symptoms and asked about their condition by open questioning, such as "How have you been feeling since you were last asked?", at least once each day while resident at the study site and at each study visit. Subjects were also be encouraged to spontaneously report AEs occurring at any other time during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Functional Director Clinical Research | Altria | 8043352366 | Jeffery.S.Edmiston@altria.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: ALCS-REG-20-15-OTDN Protocol Version 3 | Jun 30, 2021 | Mar 13, 2024 | Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: ALCS-REG-20-15-OTDN Protocol Version 2 | Apr 28, 2021 | Mar 13, 2024 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: ALCS-REG-20-15-OTDN Protocol Version 1 | Mar 9, 2021 | Mar 13, 2024 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 30, 2021 | Mar 13, 2024 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D064424 | Tobacco Use |
| D012907 | Smoking |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| OTDN Product 2 |
| Other |
Mint on!® 4 mg nicotine pouches |
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| OTDN Product 3 | Other | Mint on!® 8 mg nicotine pouches |
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| No Tobacco | Other | subjects completely stop all tobacco product usage for 7 days |
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| Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
| 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 | Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7 |
| 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. | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
| 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. | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
| 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. | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
| 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. | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
| Springfield |
| Missouri |
| 65802 |
| United States |
| NOCCR | Knoxville | Tennessee | 37920 | United States |
| Withdrawal by Subject |
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| Failure to Meet Randomization Criteria |
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| Met Eligibility Criteria But Not Needed |
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Subjects will be asked to continue smoking their UBCs ad libitum for 7 days.
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Height (cm) | Mean | Standard Deviation | cm |
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| Body Weight (kg) | Mean | Standard Deviation | kg |
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| Body Mass Index (kg/m^2) | Mean | Standard Deviation | kg/m^2 |
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| Cigarettes per Day | Mean | Standard Deviation | Cigarettes per day |
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| Years of Smoking | Mean | Standard Deviation | years |
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| Fagerström test - Total score | The Fagerström Test assesses an individual's dependence on nicotine. It consists of Yes/No and multiple choice questions where each response is assigned a value from 0 to 1 (for yes/no questions) or 0 to 3 (for multiple choice questions). Values are summed to yield a total score with a minimum score of 0 points and a maximum score of 10 points. The higher the total Fagerström score, the more intense is the subject's physical dependence on nicotine. | The Fagerström Test for Cigarette Dependence was completed on the morning of Day 1 before any study product use. Subjects in the 'Not Assigned' group were discontinued prior to administration of the Fagerström Test and, therefore, the 'Number Analyzed' for this group is '0'. | Mean | Standard Deviation | points |
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| 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 | 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. | Posted | Mean | Standard Deviation | mg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | ng/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | ng/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | pg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | Revertants / 24 hours | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | μg/g | Samples collected over 24 hours on Day -1 (baseline) and Day 7 |
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| 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 | 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. | Posted | Mean | Standard Deviation | percent saturation | Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7 |
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| 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. | 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. | Posted | Mean | Standard Deviation | cigarettes per day | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
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| 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. | 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. | Posted | Mean | Standard Deviation | nicotine pouches per day | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
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| 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. | 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. | Posted | Mean | Standard Deviation | 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 |
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| 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. | 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. | Posted | Mean | Standard Deviation | minutes | Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study |
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|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 0 |
| 2 |
| EG001 | Group 1 (CC) | Subjects will be asked to continue smoking their UBCs ad libitum for 7 days. | 0 | 29 | 0 | 29 | 5 | 29 |
| EG002 | 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 | 0 | 28 | 0 | 28 | 15 | 28 |
| EG003 | 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 | 0 | 30 | 0 | 30 | 9 | 30 |
| EG004 | 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 | 0 | 30 | 0 | 30 | 15 | 30 |
| EG005 | 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 | 0 | 29 | 0 | 29 | 12 | 29 |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Gingival discomfort | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Lip disorder | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oral discomfort | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Subcutaneous abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Tinea pedis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Eye pruritus | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
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| Unknown or Not Reported |
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| Day 7 |
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| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.4162 | Ratio of geometric LS means (Test/Ref) | 65.8 | 2-Sided | 95 | 32.0 | 135 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 1.0000 | Ratio of geometric LS means (Test/Ref) | 101 | 2-Sided | 95 | 47.5 | 215 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 2.23 | 2-Sided | 95 | 1.01 | 4.94 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 2230 | 2-Sided | 95 | 965 | 5160 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 2940 | 2-Sided | 95 | 1350 | 6400 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 4530 | 2-Sided | 95 | 2020 | 10200 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
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| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 8.08 | 2-Sided | 95 | 4.88 | 13.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 6.58 | 2-Sided | 95 | 3.88 | 11.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 6.03 | 2-Sided | 95 | 3.46 | 10.5 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9972 | Ratio of geometric LS means (Test/Ref) | 94.4 | 2-Sided | 95 | 52.7 | 169 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.4655 | Ratio of geometric LS means (Test/Ref) | 134 | 2-Sided | 95 | 77.9 | 230 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9851 | Ratio of geometric LS means (Test/Ref) | 109 | 2-Sided | 95 | 62.1 | 192 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
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| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 16.6 | 2-Sided | 95 | 12.1 | 22.6 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 13.4 | 2-Sided | 95 | 9.68 | 18.6 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 15.7 | 2-Sided | 95 | 11.2 | 22.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.7167 | Ratio of geometric LS means (Test/Ref) | 86.8 | 2-Sided | 95 | 60.6 | 124 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9864 | Ratio of geometric LS means (Test/Ref) | 105 | 2-Sided | 95 | 75.3 | 147 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.5911 | Ratio of geometric LS means (Test/Ref) | 85.1 | 2-Sided | 95 | 60.1 | 120 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 28.3 | 2-Sided | 95 | 21.5 | 37.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 33.1 | 2-Sided | 95 | 24.8 | 44.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 37.5 | 2-Sided | 95 | 27.7 | 50.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.1950 | Ratio of geometric LS means (Test/Ref) | 78.8 | 2-Sided | 95 | 57.3 | 108 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0699 | Ratio of geometric LS means (Test/Ref) | 75.5 | 2-Sided | 95 | 56.1 | 102 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.7041 | Ratio of geometric LS means (Test/Ref) | 88.3 | 2-Sided | 95 | 64.7 | 120 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 13.3 | 2-Sided | 95 | 9.84 | 17.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 13.6 | 2-Sided | 95 | 9.93 | 18.6 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 9.28 | 2-Sided | 95 | 6.67 | 12.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0404 | Ratio of geometric LS means (Test/Ref) | 143 | 2-Sided | 95 | 101 | 202 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0243 | Ratio of geometric LS means (Test/Ref) | 143 | 2-Sided | 95 | 104 | 198 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0215 | Ratio of geometric LS means (Test/Ref) | 146 | 2-Sided | 95 | 105 | 205 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 5.65 | 2-Sided | 95 | 4.01 | 7.96 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 5.61 | 2-Sided | 95 | 3.92 | 8.03 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 6.09 | 2-Sided | 95 | 4.17 | 8.89 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.8335 | Ratio of geometric LS means (Test/Ref) | 88.1 | 2-Sided | 95 | 59.4 | 131 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9622 | Ratio of geometric LS means (Test/Ref) | 92.9 | 2-Sided | 95 | 64.2 | 134 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9531 | Ratio of geometric LS means (Test/Ref) | 92.1 | 2-Sided | 95 | 62.8 | 135 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 18.0 | 2-Sided | 95 | 14.8 | 22.1 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 15.8 | 2-Sided | 95 | 12.8 | 19.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 18.2 | 2-Sided | 95 | 14.6 | 22.7 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9993 | Ratio of geometric LS means (Test/Ref) | 98.4 | 2-Sided | 95 | 78.2 | 124 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9998 | Ratio of geometric LS means (Test/Ref) | 98.9 | 2-Sided | 95 | 79.7 | 123 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.3019 | Ratio of geometric LS means (Test/Ref) | 86.4 | 2-Sided | 95 | 69.1 | 108 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 23.7 | 2-Sided | 95 | 17.6 | 31.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 19.3 | 2-Sided | 95 | 14.2 | 26.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 24.0 | 2-Sided | 95 | 17.3 | 33.3 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.1530 | Ratio of geometric LS means (Test/Ref) | 76.1 | 2-Sided | 95 | 54.0 | 107 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9999 | Ratio of geometric LS means (Test/Ref) | 98.6 | 2-Sided | 95 | 71.7 | 136 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.3025 | Ratio of geometric LS means (Test/Ref) | 80.5 | 2-Sided | 95 | 57.8 | 112 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 28.1 | 2-Sided | 95 | 21.6 | 36.6 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 27.5 | 2-Sided | 95 | 20.8 | 36.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 28.7 | 2-Sided | 95 | 21.4 | 38.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.1843 | Ratio of geometric LS means (Test/Ref) | 79.4 | 2-Sided | 95 | 58.6 | 108 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9994 | Ratio of geometric LS means (Test/Ref) | 98.1 | 2-Sided | 95 | 73.9 | 130 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9891 | Ratio of geometric LS means (Test/Ref) | 95.9 | 2-Sided | 95 | 71.4 | 129 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 44.0 | 2-Sided | 95 | 36.5 | 53.1 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 41.8 | 2-Sided | 95 | 34.4 | 50.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 42.9 | 2-Sided | 95 | 34.9 | 52.7 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.3027 | Ratio of geometric LS means (Test/Ref) | 86.9 | 2-Sided | 95 | 70.0 | 108 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9926 | Ratio of geometric LS means (Test/Ref) | 103 | 2-Sided | 95 | 83.9 | 125 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9938 | Ratio of geometric LS means (Test/Ref) | 97.5 | 2-Sided | 95 | 79.1 | 120 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 55.6 | 2-Sided | 95 | 48.0 | 64.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 52.7 | 2-Sided | 95 | 45.2 | 61.5 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 54.9 | 2-Sided | 95 | 46.7 | 64.5 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0504 | Ratio of geometric LS means (Test/Ref) | 84.4 | 2-Sided | 95 | 71.2 | 100 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9988 | Ratio of geometric LS means (Test/Ref) | 101 | 2-Sided | 95 | 86.4 | 119 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9238 | Ratio of geometric LS means (Test/Ref) | 96.0 | 2-Sided | 95 | 81.4 | 113 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 4.25 | 2-Sided | 95 | 2.28 | 7.93 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 4.24 | 2-Sided | 95 | 2.20 | 8.14 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 6.40 | 2-Sided | 95 | 3.22 | 12.7 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.1840 | Ratio of geometric LS means (Test/Ref) | 57.9 | 2-Sided | 95 | 28.3 | 119 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.3552 | Ratio of geometric LS means (Test/Ref) | 66.4 | 2-Sided | 95 | 34.0 | 130 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.3810 | Ratio of geometric LS means (Test/Ref) | 66.2 | 2-Sided | 95 | 33.0 | 133 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 20.5 | 2-Sided | 95 | 16.2 | 25.9 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 18.2 | 2-Sided | 95 | 14.3 | 23.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 17.8 | 2-Sided | 95 | 13.7 | 23.1 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9589 | Ratio of geometric LS means (Test/Ref) | 94.5 | 2-Sided | 95 | 72.0 | 124 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.4442 | Ratio of geometric LS means (Test/Ref) | 115 | 2-Sided | 95 | 89.3 | 148 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9975 | Ratio of geometric LS means (Test/Ref) | 103 | 2-Sided | 95 | 78.8 | 133 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 39.9 | 2-Sided | 95 | 27.1 | 59.0 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 30.2 | 2-Sided | 95 | 20.1 | 45.5 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0002 | Ratio of geometric LS means (Test/Ref) | 48.9 | 2-Sided | 95 | 31.9 | 75.0 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.2938 | Ratio of geometric LS means (Test/Ref) | 74.5 | 2-Sided | 95 | 47.6 | 117 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.5552 | Ratio of geometric LS means (Test/Ref) | 81.6 | 2-Sided | 95 | 53.7 | 124 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0254 | Ratio of geometric LS means (Test/Ref) | 61.7 | 2-Sided | 95 | 39.9 | 95.5 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 49.3 | 2-Sided | 95 | 39.0 | 62.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 40.8 | 2-Sided | 95 | 32.0 | 52.1 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 45.9 | 2-Sided | 95 | 35.7 | 59.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.5817 | Ratio of geometric LS means (Test/Ref) | 113 | 2-Sided | 95 | 86.8 | 148 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.8852 | Ratio of geometric LS means (Test/Ref) | 107 | 2-Sided | 95 | 83.7 | 138 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.6070 | Ratio of geometric LS means (Test/Ref) | 88.9 | 2-Sided | 95 | 68.7 | 115 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
|
| Change from Baseline to Day 7 |
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 23.8 | 2-Sided | 95 | 10.7 | 53.3 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0003 | Ratio of geometric LS means (Test/Ref) | 24.7 | 2-Sided | 95 | 10.6 | 57.4 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0002 | Ratio of geometric LS means (Test/Ref) | 22.3 | 2-Sided | 95 | 9.21 | 54.1 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.4280 | Ratio of geometric LS means (Test/Ref) | 59.1 | 2-Sided | 95 | 23.3 | 150 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9990 | Ratio of geometric LS means (Test/Ref) | 107 | 2-Sided | 95 | 44.8 | 255 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9958 | Ratio of geometric LS means (Test/Ref) | 110 | 2-Sided | 95 | 44.9 | 272 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
|
| Day 7 |
|
|
| Change from Baseline to Day 7 |
|
|
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means | -45.0 | 2-Sided | 95 | -69.6 | -20.3 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0003 | Ratio of geometric LS means | -42.3 | 2-Sided | 95 | -68.2 | -16.5 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.0004 | Ratio of geometric LS means | -44.8 | 2-Sided | 95 | -72.6 | -17.0 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9551 | Ratio of geometric LS means | -6.05 | 2-Sided | 95 | -35.2 | 23.1 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 1.0000 | Ratio of geometric LS means | -0.198 | 2-Sided | 95 | -27.3 | 26.9 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9981 | Ratio of geometric LS means | 2.48 | 2-Sided | 95 | -25.6 | 30.6 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| Day 7 |
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| Change from Baseline to Day 7 |
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| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 28.5 | 2-Sided | 95 | 17.6 | 46.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 24.3 | 2-Sided | 95 | 14.7 | 40.2 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means (Test/Ref) | 28.1 | 2-Sided | 95 | 16.6 | 47.7 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9511 | Ratio of geometric LS means (Test/Ref) | 113 | 2-Sided | 95 | 64.7 | 197 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 1.0000 | Ratio of geometric LS means (Test/Ref) | 101 | 2-Sided | 95 | 60.4 | 170 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.9003 | Ratio of geometric LS means (Test/Ref) | 86.5 | 2-Sided | 95 | 50.6 | 148 | Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group & gender included as fixed effects; baseline value included as covariate. | Superiority |
| Day 7 |
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| Change from Baseline to Day 7 |
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| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means | 43.1 | 2-Sided | 95 | 35.1 | 52.9 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means | 44.1 | 2-Sided | 95 | 35.5 | 54.6 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | <.0001 | Ratio of geometric LS means | 39.1 | 2-Sided | 95 | 31.0 | 49.4 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.2351 | Ratio of geometric LS means | 119 | 2-Sided | 95 | 93.2 | 151 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.6570 | Ratio of geometric LS means | 110 | 2-Sided | 95 | 87.7 | 138 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
| ANCOVA | Least square means (LSM) calculated from mixed model to control for variables were used for analysis instead of the observed means reported on table. | 0.5112 | Ratio of geometric LS means | 113 | 2-Sided | 95 | 89.1 | 142 | Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale. | Superiority |
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