Tobacco Dependence
Conditions
Keywords
Smoking Cessation, Nicotine
Brief summary
The purpose of this study is to assess the bioequivalence between two new oral nicotine replacement therapy products and Nicorette® microtab.
Detailed description
The trial has a single-dose, randomized, crossover design and includes 84 subjects. The investigational products will be given as single doses at separate treatment visits. Periods without Nicotine Replacement Therapy (NRT), lasting for at least 36 hours, will separate treatment visits. At each treatment visit, blood for pharmacokinetic analyses will be sampled immediately before, and at 5, 10, 15, 20, 30, and 45 minutes, as well as at 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 10 hours after start of product administration. The time until complete tablet dissolution will be recorded. Subjects will also be monitored to capture any adverse events that may occur. Treatment labels will be concealed from subjects and study personnel.
Interventions
DRUGCode STD
2 mg Single-dose of experimental nicotine product coded STD
DRUGCode STE
2 mg Single-dose of experimental nicotine product coded STE
DRUGNicorette Microtab
A comparative 2 mg Single-dose of marketed tablet
Sponsors
McNeil AB
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Healthy subjects, smoking at least 10 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 month preceding the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | During 10 hours post-dose | Cmax, which is the maximum observed plasma concentration after a dose is administered, measured in nanograms/milliliter (ng/mL) |
| Area Under the Curve [AUC(0-t)] | During 10 hours post-dose | Bioavailability within the Set Period \[AUC(0-t)\] is the area under the plasma concentration verses time curve from start of drug administration until the time of the last measurable plasma concentration, calculated as hour \* nanograms (ng) per milliliter (mL). |
| AUC(0-∞) | 10 hours post-dose | AUC (0-∞) is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. It is obtained from calculating AUC (0-t) plus AUC (t-∞). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Product Dissolution Time | During 10 hours post-dose | Product Dissolution Time is the time from administration until the investigational products were completely dissolved. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study | 84 |
| Total | 84 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age Continuous | 32.2 years STANDARD_DEVIATION 9.32 |
| Region of Enrollment Sweden | 84 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 84 | 12 / 84 | 19 / 84 |
| serious Total, serious adverse events | 0 / 84 | 0 / 84 | 0 / 84 |
Outcome results
Primary
Area Under the Curve [AUC(0-t)]
Bioavailability within the Set Period \[AUC(0-t)\] is the area under the plasma concentration verses time curve from start of drug administration until the time of the last measurable plasma concentration, calculated as hour \* nanograms (ng) per milliliter (mL).
Time frame: During 10 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STD 2 mg | Area Under the Curve [AUC(0-t)] | 12.69 hr*ng/mL | Standard Deviation 5.46 |
| STE 2 mg | Area Under the Curve [AUC(0-t)] | 12.56 hr*ng/mL | Standard Deviation 5.36 |
| Nicorette Microtab 2 mg | Area Under the Curve [AUC(0-t)] | 13.01 hr*ng/mL | Standard Deviation 5.8 |
Primary
AUC(0-∞)
AUC (0-∞) is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. It is obtained from calculating AUC (0-t) plus AUC (t-∞).
Time frame: 10 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STD 2 mg | AUC(0-∞) | 15.74 hr*ng/mL | Standard Deviation 6.33 |
| STE 2 mg | AUC(0-∞) | 15.09 hr*ng/mL | Standard Deviation 6.62 |
| Nicorette Microtab 2 mg | AUC(0-∞) | 15.57 hr*ng/mL | Standard Deviation 7.09 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Cmax, which is the maximum observed plasma concentration after a dose is administered, measured in nanograms/milliliter (ng/mL)
Time frame: During 10 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STD 2 mg | Maximum Observed Plasma Concentration (Cmax) | 3.90 ng/mL | Standard Deviation 1.35 |
| STE 2 mg | Maximum Observed Plasma Concentration (Cmax) | 4.00 ng/mL | Standard Deviation 1.37 |
| Nicorette Microtab 2 mg | Maximum Observed Plasma Concentration (Cmax) | 4.08 ng/mL | Standard Deviation 1.48 |
Secondary
Product Dissolution Time
Product Dissolution Time is the time from administration until the investigational products were completely dissolved.
Time frame: During 10 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| STD 2 mg | Product Dissolution Time | 23.3 Minutes | Standard Deviation 8.9 |
| STE 2 mg | Product Dissolution Time | 23.8 Minutes | Standard Deviation 10.22 |
| Nicorette Microtab 2 mg | Product Dissolution Time | 25.0 Minutes | Standard Deviation 6.33 |