Smoking Cessation
Conditions
Keywords
nicotine, nicotine replacement therapy, nicotine gum
Brief summary
The primary objective of this study is to compare pharmacokinetic (PK) profiles and assess the bioequivalence between the newly developed nicotine gums (2 mg and 4 mg) and the reference nicotine gums (2 mg and 4 mg) in healthy smokers.
Interventions
DRUGNicotine (2 mg)
2 mg nicotine gum in two formulations
DRUGNicotine (4 mg)
4 mg nicotine gum in two formulations
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI within the range of 19 to 30 kilograms/meters\^2 * Current cigarette smokers who have smoked daily for at least a year, and smoke their first cigarette within 30 minutes of waking up
Exclusion criteria
* Participants who have attempted to quit smoking in the last 12 months, are currently attempting to quit smoking or reduce the number of cigarettes they smoke, or are intending to quit smoking in the next 3 months, with or without use of smoking cessation aids * Treatment with known hepatic enzyme altering agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Nicotine 4 mg Test and Reference Product | Blood samples to be collected from baseline to 12 hours post-dose | Cmax for 4 mg test was compared with 4 mg reference gum |
| Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product | Blood samples to be collected from baseline to 12 hours post dose | AUC(0-t) for 2 mg test was compared with 2 mg reference gum |
| AUC(0-t) of Nicotine 4 mg Test and Reference Product | Blood samples to be collected from baseline to 12 hours post dose | AUC(0-t) of Nicotine 4 mg test was compared with 4 mg reference gum |
| Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product | Blood samples to be collected from baseline to 12 hours post dose | Cmax for 2 mg test was compared with 2 mg reference gum |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | Blood samples to be collected from baseline to 12 hours post dose | Tmax for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum |
| Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | Blood samples to be collected from baseline to 12 hours post dose | T1/2 of 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum |
| Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | Blood samples to be collected from baseline to 12 hours post dose | Kel for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum |
| Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | Blood samples to be collected from baseline to 12 hours post dose | AUC(0-∞) for 2mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum |
Countries
United Kingdom
Participant flow
Recruitment details
Potential participants were recruited at a single site in the UK.
Pre-assignment details
A total of 160 participants were screened for this study, of which 84 participants were randomized. Seventy seven participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Total Participants | 84 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Study Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Washout Period Before Study Period 2 | Adverse Event | 1 | 1 | 0 | 0 |
| Washout Period Before Study Period 2 | Other reason | 1 | 0 | 0 | 0 |
| Washout Period Before Study Period 3 | Other reason | 1 | 0 | 0 | 0 |
| Washout Period Before Study Period 4 | Positive alcohol test | 1 | 0 | 0 | 0 |
| Washout Period Before Study Period 4 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Participants |
|---|---|
| Age, Continuous | 26.8 Years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 44 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 | 11 / 82 | 12 / 77 | 12 / 79 | 11 / 81 |
| serious Total, serious adverse events | 0 / 82 | 0 / 77 | 0 / 79 | 0 / 81 |
Outcome results
Primary
Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product
AUC(0-t) for 2 mg test was compared with 2 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nicotine Gum (2 mg) | Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product | 11.49 hr*ng/mL | Standard Deviation 4.224 |
| Reference Nicotine Gum (2 mg) | Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product | 10.24 hr*ng/mL | Standard Deviation 3.768 |
Comparison: Null hypothesis stated that there was no difference between the test and reference gums in AUC(0-t)90% CI: [1.07, 1.147]ANOVA
Primary
AUC(0-t) of Nicotine 4 mg Test and Reference Product
AUC(0-t) of Nicotine 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1of 4 treatment sequences; took atleast one dose of study medication (both test and ref) in 2 mg dose and/or in 4 mg doses; did not have any AE assimilated to vomiting in first 4h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nicotine Gum (2 mg) | AUC(0-t) of Nicotine 4 mg Test and Reference Product | 23.44 hr*ng/mL | Standard Deviation 7.593 |
| Reference Nicotine Gum (2 mg) | AUC(0-t) of Nicotine 4 mg Test and Reference Product | 21.50 hr*ng/mL | Standard Deviation 6.874 |
Comparison: Null hypothesis stated that there was no difference between the test and reference gums in AUC(0-t)90% CI: [1.061, 1.137]ANOVA
Primary
Cmax of Nicotine 4 mg Test and Reference Product
Cmax for 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post-dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nicotine Gum (2 mg) | Cmax of Nicotine 4 mg Test and Reference Product | 7.49 ng/mL | Standard Deviation 1.72 |
| Reference Nicotine Gum (2 mg) | Cmax of Nicotine 4 mg Test and Reference Product | 6.98 ng/mL | Standard Deviation 1.777 |
Comparison: Null hypothesis stated that there was no difference between the test and reference gums in Cmax90% CI: [1.028, 1.116]ANOVA
Primary
Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product
Cmax for 2 mg test was compared with 2 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nicotine Gum (2 mg) | Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product | 3.93 ng/mL | Standard Deviation 1.232 |
| Reference Nicotine Gum (2 mg) | Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product | 3.72 ng/mL | Standard Deviation 1.289 |
Comparison: Null hypothesis stated that there was no difference between the test and reference gums in Cmax90% CI: [1.002, 1.089]ANOVA
Secondary
Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products
T1/2 of 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Nicotine Gum (2 mg) | Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 2.12 hr |
| Reference Nicotine Gum (2 mg) | Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 2.03 hr |
| Test Nicotine Gum (4 mg) | Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 2.01 hr |
| Reference Nicotine Gum (4 mg) | Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 2.02 hr |
Secondary
Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products
Kel for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Nicotine Gum (2 mg) | Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.33 1/hr |
| Reference Nicotine Gum (2 mg) | Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.34 1/hr |
| Test Nicotine Gum (4 mg) | Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.34 1/hr |
| Reference Nicotine Gum (4 mg) | Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.34 1/hr |
Secondary
Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products
AUC(0-∞) for 2mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nicotine Gum (2 mg) | Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 12.56 hr*ng/mL | Standard Deviation 4.409 |
| Reference Nicotine Gum (2 mg) | Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 11.20 hr*ng/mL | Standard Deviation 3.955 |
| Test Nicotine Gum (4 mg) | Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 24.60 hr*ng/mL | Standard Deviation 7.845 |
| Reference Nicotine Gum (4 mg) | Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 22.64 hr*ng/mL | Standard Deviation 7.136 |
Secondary
Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products
Tmax for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum
Time frame: Blood samples to be collected from baseline to 12 hours post dose
Population: Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration \>5% of Cmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Nicotine Gum (2 mg) | Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.75 hr |
| Reference Nicotine Gum (2 mg) | Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.75 hr |
| Test Nicotine Gum (4 mg) | Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.75 hr |
| Reference Nicotine Gum (4 mg) | Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products | 0.75 hr |