Smoking Cessation
Conditions
Keywords
nicotine lozenge, nicotine, nicotine replacement therapy
Brief summary
To compare the bio equivalence of new nicotine lozenge formulation with the reference nicotine lozenge so as to deliver the same nicotine blood profile.
Interventions
DRUGNicotine (2 mg)
2 mg nicotine lozenge in two formulations
DRUGNicotine (4 mg)
4 mg nicotine lozenge in two formulations
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must be healthy smokers who usually smoked their first cigarette within 30 minutes of waking. * Body Mass Index within the range 19-27 kilograms/meters\^2
Exclusion criteria
* Participants who used chewing tobacco or tobacco products other than cigarettes within 21 days of screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | AUC(0-t) was evaluated using the trapezoid rule. |
| Maximum Observed Plasma Concentration [Cmaximum (Max)] | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | Cmax was depicted from plasma concentration of nicotine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC [0-infinity (Inf)] | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | AUC (0-inf) was evaluated using the trapezoid rule. |
| Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | Tmax was time at which Cmax of nicotine was reached. |
| Apparent Elimination Half-life of Nicotine T(1/2) | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | T(1/2) was calculated using plasma time-concentration values. |
| Elimination Rate Constant for Plasma Nicotine: K (el) | Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours | Kel was calculated with the help of plasma time concentration values. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Out of 141 participants screened, only 50 were randomized since 91 were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants were evaluated for baseline measures | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 3 | Adverse Event | 0 | 0 | 0 | 1 |
| Washout Period 1 | Withdrawal by Subject | 1 | 2 | 0 | 0 |
| Washout Period 2 | Adverse Event | 1 | 0 | 0 | 0 |
| Washout Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 |
| Washout Period 3 | Adverse Event | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age Continuous | 30.3 Years STANDARD_DEVIATION 9.58 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 47 | 9 / 46 | 13 / 45 | 15 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 46 | 0 / 45 | 1 / 47 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)]
AUC(0-t) was evaluated using the trapezoid rule.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg Cherry Lozenge | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] | 18.84 nanogram (ng).hour (hr)/millilitre (mL) | Standard Deviation 7.07 |
| 2mg Mint Lozenge | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] | 20.71 nanogram (ng).hour (hr)/millilitre (mL) | Standard Deviation 7.42 |
| 4mg Cherry Lozenge | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] | 34.71 nanogram (ng).hour (hr)/millilitre (mL) | Standard Deviation 14.48 |
| 4mg Mint Lozenge | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] | 33.68 nanogram (ng).hour (hr)/millilitre (mL) | Standard Deviation 12.17 |
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.88, 0.94]Wilcoxon Signed Rank Test
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.98, 1.05]Wilcoxon Signed Rank test
Primary
Maximum Observed Plasma Concentration [Cmaximum (Max)]
Cmax was depicted from plasma concentration of nicotine.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg Cherry Lozenge | Maximum Observed Plasma Concentration [Cmaximum (Max)] | 5.67 ng/mL | Standard Deviation 1.53 |
| 2mg Mint Lozenge | Maximum Observed Plasma Concentration [Cmaximum (Max)] | 6.35 ng/mL | Standard Deviation 1.43 |
| 4mg Cherry Lozenge | Maximum Observed Plasma Concentration [Cmaximum (Max)] | 9.37 ng/mL | Standard Deviation 2.63 |
| 4mg Mint Lozenge | Maximum Observed Plasma Concentration [Cmaximum (Max)] | 9.72 ng/mL | Standard Deviation 2.7 |
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.85, 0.94]Wilcoxon Signed Rank Test
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.93, 1.02]Wilcoxon Signed Rank Test
Secondary
Apparent Elimination Half-life of Nicotine T(1/2)
T(1/2) was calculated using plasma time-concentration values.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2mg Cherry Lozenge | Apparent Elimination Half-life of Nicotine T(1/2) | 3.39 hr |
| 2mg Mint Lozenge | Apparent Elimination Half-life of Nicotine T(1/2) | 3.41 hr |
| 4mg Cherry Lozenge | Apparent Elimination Half-life of Nicotine T(1/2) | 3.19 hr |
| 4mg Mint Lozenge | Apparent Elimination Half-life of Nicotine T(1/2) | 3.13 hr |
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.5619Wilcoxon Signed Rank Test
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.4523Wilcoxon Signed Rank Test
Secondary
AUC [0-infinity (Inf)]
AUC (0-inf) was evaluated using the trapezoid rule.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg Cherry Lozenge | AUC [0-infinity (Inf)] | 21.03 ng.hr/mL | Standard Deviation 8.05 |
| 2mg Mint Lozenge | AUC [0-infinity (Inf)] | 22.66 ng.hr/mL | Standard Deviation 8.48 |
| 4mg Cherry Lozenge | AUC [0-infinity (Inf)] | 37.48 ng.hr/mL | Standard Deviation 16.87 |
| 4mg Mint Lozenge | AUC [0-infinity (Inf)] | 36.08 ng.hr/mL | Standard Deviation 13.96 |
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.88, 0.95]Wilcoxon Signed Rank Test
Comparison: The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.90% CI: [0.98, 1.06]Wilcoxon Signed Rank Test
Secondary
Elimination Rate Constant for Plasma Nicotine: K (el)
Kel was calculated with the help of plasma time concentration values.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2mg Cherry Lozenge | Elimination Rate Constant for Plasma Nicotine: K (el) | 0.20 1/hr |
| 2mg Mint Lozenge | Elimination Rate Constant for Plasma Nicotine: K (el) | 0.20 1/hr |
| 4mg Cherry Lozenge | Elimination Rate Constant for Plasma Nicotine: K (el) | 0.22 1/hr |
| 4mg Mint Lozenge | Elimination Rate Constant for Plasma Nicotine: K (el) | 0.22 1/hr |
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.5113Wilcoxon Signed Rank Test
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.537Wilcoxon Signed Rank Test
Secondary
Time to Reach Maximum Plasma Nicotine Concentration (Tmax)
Tmax was time at which Cmax of nicotine was reached.
Time frame: Blood samples taken pre-dose and post-dose at 3, 5, 10, 15, 20, 30, 40, and 50 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours
Population: Analysis was done per intention to treat (ITT) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2mg Cherry Lozenge | Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | 0.83 hr |
| 2mg Mint Lozenge | Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | 0.67 hr |
| 4mg Cherry Lozenge | Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | 0.83 hr |
| 4mg Mint Lozenge | Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | 0.83 hr |
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.1491Wilcoxon Signed Rank Test
Comparison: The null hypothesis considered that there is no median within-subject difference between two treatment groups.p-value: 0.679Wilcoxon Signed Rank Test