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This is a randomized, open-label, single-dose, three-period, crossover, single-center comparative bioavailability (BA) study under fasting condition in Chinese healthy male adult participants with a history of cigarette smoking. The participants will be admitted to the investigational clinic at least 38 hours before dosing and will remain domiciled until the completion of all study procedures at approximately 24 hours after dosing. Three toothpastes (one is commercial non-medicated non-nicotine containing chewing gum and other two are nicotine containing gums) will be provided across the 3 treatment periods. During each of the 3 treatment periods, participants will be under supervision in a non-smoking area and will abstain from smoking.There will be a total of at least 7 days and not more than 10 days (clinical furlough period) between treatment periods. Twenty (20) blood samples will be collected for pharmacokinetic (PK) analysis at baseline and multiple time points following study drug administration. The trial duration will be approximately 49 days and up to 55 days from screening to study end including the screening period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A:Treatment B:Treatment C | Other | Participants will be administered with Treatment A(Nicorette 2 mg coated mint gum) followed by Treatment B (Nicotinell 2 mg coated mint gum) followed by Treatment C (Nicotinell 2 mg coated fruit flavor gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Treatment B:Treatment C:Treatment A | Other | Participants will be administered with Treatment B (Nicotinell 2 mg coated mint gum) followed by Treatment C (Nicotinell 2 mg coated fruit flavor gum) followed by Treatment A(Nicorette 2 mg coated mint gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Treatment C:Treatment A:Treatment B | Other | Participants will be administered with Treatment C (Nicotinell 2 mg coated fruit flavor gum) followed by Treatment A(Nicorette 2 mg coated mint gum) followed by Treatment B (Nicotinell 2 mg coated mint gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment A: Nicorette 2 mg coated mint gum | Other | Participants will be administered with 2 mg coated mint gum of Nicorette |
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| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve from time zero to last sampling time [AUC(0-t)] | AUC(0-t) will be calculated using the trapezoidal rule. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Area under the curve from time zero extrapolated to infinity [AUC(0-inf)] | The area under the plasma concentration versus time curve will be calculated from time 0 to infinity where AUC = AUClast + Clast/λz Clast is the concentration at the last measurable sampling time point and λz is the terminal elimination rate constant. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Maximum plasma concentration (Cmax) | Cmax will be obtained graphically from the plasma concentration over time profile. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Time to reach maximum plasma concentration (Tmax) | Tmax will be obtained graphically from the plasma concentration over time profile. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Termination rate constant (Lambda_z) | Lambda_z will be computed as the slope of the regression line of ln (C(t)) on time. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Elimination half life (t1/2) |
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Inclusion Criteria:
Exclusion Criteria:-
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Beijing | 100032 | China |
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| Treatment A: Treatment C:Treatment B |
| Other |
Participants will be administered with Treatment A (Nicorette 2 mg coated mint gum) followed by Treatment C (Nicotinell 2 mg coated fruit flavor gum) followed by Treatment B (Nicotinell 2 mg coated mint gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Treatment B:Treatment A: Treatment C | Other | Participants will be administered with Treatment B (Nicotinell 2 mg coated mint gum) followed by Treatment A (Nicorette 2 mg coated mint gum) followed by Treatment C (Nicotinell 2 mg coated fruit flavor gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Treatment C:Treatment B:Treatment A | Other | Participants will be administered with Treatment C (Nicotinell 2 mg coated fruit flavor gum) followed by Treatment B (Nicotinell 2 mg coated mint gum) followed by Treatment A (Nicorette 2 mg coated mint gum). Administration of each treatment will be separated by clinical furlough period of at least 7 days and not more than 10 days. |
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| Treatment B: Nicotinell 2 mg coated mint gum | Other | Participants will be administered with 2 mg coated mint gum of Nicotinell |
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| Treatment C: Nicotinell 2 mg coated fruit flavor gum | Other | Participants will be administered with 2 mg coated fruit flavor gum of Nicotinell |
|
T1/2 will be computed as T1/2 = 0.693/ λz. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration.
| 2 days |
| Systemic clearance (CL/F) | CL/F will be calculated as the Dose/AUCinf, where Dose is the actual nicotine dose released. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| Apparent volume of distribution (Vd/F) | Vd/F will be determined by the following equation: Vz/F = Dose/(lambda_z · AUCinf), where Dose is the actual nicotine dose released. Twenty (20) blood samples will be collected at baseline and multiple timepoints following study drug administration. | 2 days |
| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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