This is a research study to verify the same effectiveness and safety profile for the test products, nicotine 2 mg gum and nicotine 4 mg gum, as for the already approved products, Nicorette Mint 2 mg gum and Nicorette Mint 4 mg gum (reference products), in a standardized mode. This verification is done in a so-called bioequivalence study, which means that the same amount of the same active substance (nicotine), in the same dosage form, for the same route of administration, and meeting the same or comparable standards is performed. During the study visits, blood samples will be drawn to measure the level of the substance in the blood to verify that the two test products are comparable to the reference products. Tolerability of the treatments will be evaluated based on reported and observed adverse events.
This is a single-center, randomized, single-dose open-label, cross-over study in 76 healthy males and females in total. The investigational products (IPs), i.e., Nicorette Extra Mint Gum 2 and 4 mg, and Nicorette Mint Gum 2 and 4 mg, will be given as single doses at separate treatment visits. Investigational treatments will be separated by at least 36 hours. Blood samples for determination of nicotine will be drawn pre-dose (within 5 minutes of administering, i.e., start of chewing) and at 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration. Used gums will be collected and analyzed to determine the amount of remaining nicotine. Any Adverse Events (AEs) that may occur will be registered.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
76
A single dose of one nicotine gum will be placed on the tongue to be chewed every 2 seconds for 30 minutes.
A single dose of one nicotine gum will be placed on the tongue to be chewed every 2 seconds for 30 minutes.
A single dose of one nicotine gum will be placed on the tongue to be chewed every 2 seconds for 30 minutes.
A single dose of one nicotine gum will be placed on the tongue to be chewed every 2 seconds for 30 minutes.
Beijing Hospital, No.1
Beijing, China
Peak Plasma Concentration (Cmax) of nicotine.
The maximum observed plasma concentration (Cmax).
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
Area under the plasma concentration versus time curve (AUCt) from start of nicotine administration until the last measurable concentration.
AUCt is defined as area under the plasma concentration versus time curves from start of drug administration until the last measureable concentration.
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
Area under the plasma concentration versus time curve (AUC∞) of nicotine.
AUC∞ is defined as area under the plasma concentration versus time curves from start of drug administration until the nicotine plasma concentration is negligible (infinity).
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
The extrapolated part of area under the plasma concentration versus time curve (AUC∞) of nicotine.
The area under the plasma concentration versus time curves from start of drug administration until 48 hours (infinity).
Time frame: Extrapolation from 12 hours after start of drug administration until 48 hours.
The time at which the maximum nicotine concentration (Cmax) occurs (Tmax).
Tmax is defined as the time point at which the maximum nicotine concentration (Cmax) occurs.
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
Determination of the terminal elimination rate constant (lambda_z) for nicotine.
The rate at which the drug is removed from the body system.
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
The plasma half-life (t1/2) of nicotine.
The time taken for the nicotine plasma concentration to fall to half its original value.
Time frame: At baseline, 5, 10, 15, 20, 30, 45, and 60 minutes, as well as 1.5, 2, 4, 6, 7, 8, 9, and 10 hours after start of administration.
Amount of nicotine extracted from Nicorette Mint 2 mg gums.
The residual amount of nicotine in the chewed gums will be analyzed and subtracted from the original amount of nicotine in the gums, and summarized descriptively.
Time frame: After 30 minutes of chewing.
Amount of nicotine extracted from Nicorette Mint 4 mg gums.
The residual amount of nicotine in the chewed gums will be analyzed and subtracted from the original amount of nicotine in the gums, and summarized descriptively.
Time frame: After 30 minutes of chewing.
Amount of nicotine extracted from Nicorette Extra Mint 2 mg gums.
The residual amount of nicotine in the chewed gums will be analyzed and subtracted from the original amount of nicotine in the gums, and summarized descriptively.
Time frame: After 30 minutes of chewing.
Amount of nicotine extracted from Nicorette Extra Mint 4 mg gums.
The residual amount of nicotine in the chewed gums will be analyzed and subtracted from the original amount of nicotine in the gums, and summarized descriptively.
Time frame: After 30 minutes of chewing.
Percentage of Subjects with Treatment-Emergent Adverse Events after single-dose administration of investigational product.
Percentage of subjects experiencing treatment-emergent adverse events by treatment, system organ class and preferred term.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion for any unresolved adverse events.
Percentage of Subjects with Treatment-Emergent Adverse Events after single-dose administration of investigational product - by worst-case severity.
Percentage (%) of subjects experiencing treatment-emergent adverse events by treatment, system organ class, preferred term and severity.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion for any unresolved adverse events.
Percentage of Subjects with common treatment-emergent adverse events (AEs) after single-dose administration of Investigational product.
Percentage (%) of subjects with commonly reported treatment-emergent adverse events by system organ class and preferred term.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion for any unresolved adverse events.
Percentage of Subjects with treatment-related adverse events (AEs) after single-dose administration of investigational product.
Percentage (%) of subjects experiencing treatment-related adverse events by treatment, system organ class and preferred term.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion for any unresolved adverse event.
Percentage of Subjects with treatment-related adverse events (AEs) after single-dose administration of investigational product - by worst-case severity.
Percentage (%) of subjects experiencing treatment-related adverse events by treatment, system organ class, preferred term and severity.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion for any unresolved adverse events.
Percentage of Subjects with treatment-emergent serious adverse events (SAEs).
Percentage (%) of subjects experiencing treatment-emergent serious adverse events.
Time frame: From first dose received up to 2.5 weeks + 30 days follow up after study completion.
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