Tobacco Dependence
Conditions
Keywords
Smoking Cessation, Nicotine pharmacokinetics
Brief summary
A comparison of three products for oral nicotine replacement with respect to pharmacokinetics after single-dose of nicotine.
Detailed description
This study compares a new oral Nicotine Replacement Therapy (NRT) product with NiQuitin™ lozenge 4 mg and Nicorette®gum 4 mg, after 12 hours of nicotine abstinence, with respect to nicotine pharmacokinetics, during 12 hours after start of administration. Single doses of each treatment are given once in the morning during five separate treatment visits scheduled in a crossover setting with randomized treatment sequences. The study will include 45 healthy smokers between 18-50 years, who have been smoking at least 15 cigarettes daily during at least one year preceding inclusion. Subjects and study personnel will be aware of which treatment is administered at a given visit.
Interventions
DRUGOral Nicotine
A new l mg oral nicotine product
DRUGNiQuitinTM Nicotine Lozenge
A marketed 4 mg Nicotine lozenge
DRUGNicorette® Nicotine Gum
A marketed 4 mg Nicotine Gum
Sponsors
McNeil AB
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Healthy smokers, smoking at least 15 cigarettes daily during at least one year preceding inclusion and BMI between 17.5 and 30.0 kg/m2. * Female participants of child-bearing potential are required to use a medically acceptable means of birth control. * A personally signed and dated informed consent document, indicating that the subject has been informed of all pertinent aspects of the study.
Exclusion criteria
* Pregnancy, lactation or intended pregnancy. * Treatment with an investigational product or donation or loss of blood within 3 months preceding the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration | During 12 hours after start of administration | Cmax, which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered measured in nanograms/milliliter (ng/ml) |
| Bioavailability | 12 hours | A measure of how much of the drug reaches a person's bloodstream within a given period of time for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The area under the curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period to form a curve. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour\*nanograms/milliliter (h\*ng/ml). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Plasma Concentration | During 10 minutes after start of administration | Area under the nicotine plasma concentration curve at 10 minutes (AUC10 min) |
| Time of Maximum Concentration | During 12 hours after start of administration | The time at which maximum concentration is reached (Tmax) |
| Terminal Elimination Rate Constant | During 12 hours after start of administration | The terminal nicotine elimination rate constant (Lamda z) |
| Released Nicotine | After 30 minutes' chewing | The amount of nicotine released from Nicorette® gum 4 mg during 30 minutes' chewing |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Full Safety Set | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline | Withdrawal by Subject | 2 |
| Nicorette® Gum | Withdrawal by Subject | 1 |
| NiQuitinTM Lozenge | Withdrawal by Subject | 1 |
| Oral Nicotine 1 | Withdrawal by Subject | 1 |
| Washout Period 4 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Region of Enrollment Sweden | 45 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 41 | 11 / 42 | 24 / 43 | 7 / 43 | 9 / 42 |
| serious Total, serious adverse events | 0 / 41 | 1 / 42 | 0 / 43 | 0 / 43 | 0 / 42 |
Outcome results
Primary
Bioavailability
A measure of how much of the drug reaches a person's bloodstream within a given period of time for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The area under the curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period to form a curve. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour\*nanograms/milliliter (h\*ng/ml).
Time frame: 12 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Nicotine 1 | Bioavailability | AUC to last measurable concentration | 5.85 h*ng/ml | Standard Deviation 3.7 |
| Oral Nicotine 1 | Bioavailability | AUC to infinity | 7.54 h*ng/ml | Standard Deviation 4.1 |
| Oral Nicotine 2 | Bioavailability | AUC to last measurable concentration | 11.50 h*ng/ml | Standard Deviation 3.98 |
| Oral Nicotine 2 | Bioavailability | AUC to infinity | 13.30 h*ng/ml | Standard Deviation 4.2 |
| Oral Nicotine 4 | Bioavailability | AUC to last measurable concentration | 21.96 h*ng/ml | Standard Deviation 9 |
| Oral Nicotine 4 | Bioavailability | AUC to infinity | 24.10 h*ng/ml | Standard Deviation 9.35 |
| NiQuitinTM Lozenge 4 mg | Bioavailability | AUC to infinity | 24.30 h*ng/ml | Standard Deviation 11.91 |
| NiQuitinTM Lozenge 4 mg | Bioavailability | AUC to last measurable concentration | 22.00 h*ng/ml | Standard Deviation 11.05 |
| Nicorette® Gum 4 mg | Bioavailability | AUC to last measurable concentration | 19.69 h*ng/ml | Standard Deviation 7.95 |
| Nicorette® Gum 4 mg | Bioavailability | AUC to infinity | 21.62 h*ng/ml | Standard Deviation 8.43 |
Primary
Maximum Plasma Concentration
Cmax, which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered measured in nanograms/milliliter (ng/ml)
Time frame: During 12 hours after start of administration
Population: ITT
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Nicotine 1 | Maximum Plasma Concentration | 3.04 (ng/ml) | Standard Deviation 1.47 |
| Oral Nicotine 2 | Maximum Plasma Concentration | 4.94 (ng/ml) | Standard Deviation 2.06 |
| Oral Nicotine 4 | Maximum Plasma Concentration | 8.63 (ng/ml) | Standard Deviation 2.96 |
| NiQuitinTM Lozenge 4 mg | Maximum Plasma Concentration | 6.44 (ng/ml) | Standard Deviation 2.06 |
| Nicorette® Gum 4 mg | Maximum Plasma Concentration | 7.36 (ng/ml) | Standard Deviation 2.66 |
Secondary
Nicotine Plasma Concentration
Area under the nicotine plasma concentration curve at 10 minutes (AUC10 min)
Time frame: During 10 minutes after start of administration
Population: ITT
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Nicotine 1 | Nicotine Plasma Concentration | 0.43 (h*ng/ml) | Standard Deviation 0.23 |
| Oral Nicotine 2 | Nicotine Plasma Concentration | 0.56 (h*ng/ml) | Standard Deviation 0.33 |
| Oral Nicotine 4 | Nicotine Plasma Concentration | 0.87 (h*ng/ml) | Standard Deviation 0.42 |
| NiQuitinTM Lozenge 4 mg | Nicotine Plasma Concentration | 0.29 (h*ng/ml) | Standard Deviation 0.2 |
| Nicorette® Gum 4 mg | Nicotine Plasma Concentration | 0.29 (h*ng/ml) | Standard Deviation 0.2 |
Secondary
Released Nicotine
The amount of nicotine released from Nicorette® gum 4 mg during 30 minutes' chewing
Time frame: After 30 minutes' chewing
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Nicotine 1 | Released Nicotine | 2.70 (ng/ml) | Standard Deviation 0.27 |
Secondary
Terminal Elimination Rate Constant
The terminal nicotine elimination rate constant (Lamda z)
Time frame: During 12 hours after start of administration
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Nicotine 1 | Terminal Elimination Rate Constant | 0.29 (1/hr) | Standard Deviation 0.13 |
| Oral Nicotine 2 | Terminal Elimination Rate Constant | 0.29 (1/hr) | Standard Deviation 0.1 |
| Oral Nicotine 4 | Terminal Elimination Rate Constant | 0.30 (1/hr) | Standard Deviation 0.1 |
| NiQuitinTM Lozenge 4 mg | Terminal Elimination Rate Constant | 0.26 (1/hr) | Standard Deviation 0.07 |
| Nicorette® Gum 4 mg | Terminal Elimination Rate Constant | 0.31 (1/hr) | Standard Deviation 0.1 |
Secondary
Time of Maximum Concentration
The time at which maximum concentration is reached (Tmax)
Time frame: During 12 hours after start of administration
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Nicotine 1 | Time of Maximum Concentration | 0.17 (hours) |
| Oral Nicotine 2 | Time of Maximum Concentration | 0.21 (hours) |
| Oral Nicotine 4 | Time of Maximum Concentration | 0.17 (hours) |
| NiQuitinTM Lozenge 4 mg | Time of Maximum Concentration | 0.75 (hours) |
| Nicorette® Gum 4 mg | Time of Maximum Concentration | 0.50 (hours) |