Nicotine Pharmacokinetics and Subjective Effects of Nicotine Pouch 1.0 Compared to Velo® Ice Cool and Zyn® Cool Mint Mini Dry in Healthy Smokers

Study Overview
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Brief Summary
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This is a single-center, randomized, controlled, open-label, cross-over study in healthy smoking subjects to investigate the nicotine pharmacokinetic (PK) profiles of 4 variants of Nicotine pouch 1.0 compared to marketed Velo - Nicotine Pouch (NP) and Zyn-NP. In addition, pharmacodynamic (PD) effects will be evaluated to provide further insights on Nicotine pouch 1.0 product acceptance and abuse liability. The study will be conducted with 3 periods and 6 sequences in a Williams design (cross-over).

Detailed Description
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The purpose of the study is to evaluate the nicotine PK profiles of 4 variants of NP 1.0 versus Velo-NP and Zyn-NP following a 30-minute use period. In addition, PD, including subjective effects and related behavioral assessments will be evaluated, to provide further insights on NP 1.0 product acceptance and abuse liability. Safety will be assessed throughout the study. The aim is to evaluate if NP 1.0 can provide an acceptable alternative to smoking cigarettes in terms of both, nicotine delivery and sensorial satisfaction for smokers who would otherwise continue smoking cigarettes.

Official Title
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A Single-center, Randomized, Controlled, Open-label Study to Investigate the Nicotine Pharmacokinetic Profiles and Subjective Effects of Four Variants of Nicotine Pouch 1.0 Compared to Velo® Ice Cool and Zyn® Cool Mint Mini Dry in Healthy Smokers

Conditions
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Smoking, Nicotine

Intervention / Treatment
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* Other: NP-1
* Other: NP-2
* Other: NP-3
* Other: NP-4
* Other: Velo-NP
* Other: Zyn-NP


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Subject has smoked continuously for at least the last 3 years prior to the Screening visit. Subject has smoked ≥ 10 commercially available cigarettes per day for 4 weeks prior to Screening Visit and Admission. Smoking status will be verified based on a urinary cotinine test (cotinine ≥ 500 ng/mL). Subject does not plan to quit using tobacco and/or nicotine products within the next 3 months. Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period. Main Exclusion Criteria: As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical. Subject is legally incompetent, or physically or mentally incapable of giving consent. Subject has a clinically relevant disease that requires medication, which as per the judgment of the Investigator would jeopardize the safety of the subject. Subject has donated or received whole blood or blood products within 30 days prior to Screening Visit. Subject has a BMI < 18.5 kg/m2 or > 32.0 kg/m2 (Europe) or > 35.0 kg/m2 (USA). For women only: subject is pregnant (does not have negative pregnancy test at Screening Visit and at Admission) or is breastfeeding.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NP-1<br>Nicotine Pouch 1.0 (variant NP-1) | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|
| Experimental: NP-2<br>Nicotine Pouch 1.0 (variant NP-2) | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|
| Experimental: NP-3<br>Nicotine Pouch 1.0 (variant NP-3) | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|
| Experimental: NP-4<br>Nicotine Pouch 1.0 (variant NP-4) | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|
| Active Comparator: Velo-NP<br>Velo® Ice Cool | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|
| Active Comparator: Zyn-NP<br>Zyn® Cool Mint Mini Dry | Other: NP-1<br>* NP-1; 8.4 mg nicotine; pH 8.0; moisture 30<br>Other: NP-2<br>* NP-2; 8.4 mg nicotine; pH 9.0; moisture 30<br>Other: NP-3<br>* NP-3; 3.6 mg nicotine; pH 8.0; moisture 15<br>Other: NP-4<br>* NP-4; 3.6 mg nicotine; pH 8.0; moisture 30<br>Other: Velo-NP<br>* Velo-NP; 10 mg nicotine;<br>Other: Zyn-NP<br>* Zyn-NP; 3 mg nicotine;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Background-corrected maximum plasma concentration [Cmax] | To measure the background-corrected maximum plasma concentration [Cmax] of 4 variants of NP 1.0 nicotine pouches compared to Velo-NP and Zyn-NP in healthy smokers from a 30 minutes product use period. | Measured at baseline (day 1), day 2, and day 3 | 
| Background-corrected time to the maximum concentration [Tmax] | To measure the background-corrected time to the maximum concentration [Tmax] of 4 variants of NP 1.0 nicotine pouches compared to Velo-NP and Zyn-NP in healthy smokers from a 30 minutes product use period. | Measured at baseline (day 1), day 2, and day 3 | 
| Area under the background-corrected concentration-time curve (AUC) from start of product use | To measure the area under the background-corrected concentration-time curve (AUC) from start of product use of 4 variants of NP 1.0 nicotine pouches compared to Velo-NP and Zyn-NP in healthy smokers from a 30 minutes product use period. | Measured at baseline (day 1), day 2, and day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of cigarette craving by the visual analog sale (VAS)-craving assessment | To measure cigarette craving by the visual analog sale (VAS)-craving assessment in healthy smokers following a 30 minutes product use period of 4 variants of Nicotine pouch 1.0 compared to Velo-NP and Zyn-NP. | Measured at baseline (day 1), day 2, and day 3 | 
| Score of in the moment product liking by the VAS-liking assessment | To measure in the moment product liking by the VAS-liking assessment in healthy smokers following a 30 minutes product use period of 4 variants of Nicotine pouch 1.0 compared to Velo-NP and Zyn-NP. | Measured at baseline (day 1), day 2, and day 3 | 
| Score of overall product liking by the VAS-liking assessment | To measure overall product liking by the VAS-liking assessment in healthy smokers following a 30 minutes product use period of 4 variants of Nicotine pouch 1.0 compared to Velo-NP and Zyn-NP. | Measured at baseline (day 1), day 2, and day 3 | 
| Score of product satisfaction by the VAS-satisfaction assessment | To measure product satisfaction by the VAS-satisfaction assessment in healthy smokers following a 30 minutes product use period of 4 variants of Nicotine pouch 1.0 compared to Velo-NP and Zyn-NP. | Measured at baseline (day 1), day 2, and day 3 | 
| Score of product intention to use again by the VAS-intention to use again assessment | To measure intention to use product again by the VAS-intention to use again assessment in healthy smokers following a 30 minutes product use period of 4 variants of Nicotine pouch 1.0 compared to Velo-NP and Zyn-NP. | Measured at baseline (day 1), day 2, and day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine-containing products, Nicotine delivery