Smoking Cessation
Conditions
Brief summary
This is a randomized, single center, open label, single dose, four way crossover study in fasted healthy male subjects to compare the pharmacokinetics of nicotine following administration of 3 prototype 4mg nicotine lozenge to an internationally marketed 4mg nicotine lozenge. Blood samples will be drawn at pre-specified intervals for a total of 12 hours post dose in each treatment session and plasma samples analyzed for nicotine levels.
Interventions
DRUGnicotine
4 mg nicotine lozenge experimental
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
\- smoked commercially-manufactured cigarettes daily for the preceding 12 months and routinely smokes first cigarette within 30mins of awakening.
Exclusion criteria
* inability to refrain from smoking during confinement period, smoking tobacco in any other form other than commercially manufactured cigarettes, subject has used chewing tobacco or other tobacco products other than commercially manufactured cigarettes within 7 days of dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to t, AUC (0-t) | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined from plasma concentration time profile of nicotine. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data. |
| Maximum Plasma Concentration (Cmax) | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Maximum plasma nicotine concentration was determined from plasma-concentration time profiles. Cmax was based on the baseline adjusted nicotine plasma concentration data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Area under the plasma nicotine concentration-time curve from zero extrapolated to infinity was determined. AUC(0-inf) was based on the baseline adjusted nicotine plasma concentration data. |
| Time to Maximum Plasma Concentration (Tmax) | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Tmax was determined from plasma concentration time profiles. Tmax was based on the baseline adjusted nicotine plasma concentration data. |
| Rate of Elimination (Kel) | Blood samples were collected pre-dose at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data. |
| Plasma Half Life (t1/2) | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | Half-life of elimination of nicotine was determined. t1/2 was based on the baseline adjusted nicotine plasma concentration data. |
Countries
India
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
A total of 102 participants were screened, of which only 40 were randomized into the study. Fourteen participants did not meet the study criteria, 32 were lost to follow up, 2 withdrew consent while remaining 14 were not randomized due to other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population Baseline measurements were performed for safety population which included all participants in the study who were dispensed at least one of the study treatment. Out of 40 randomized participants, one participant did not receive any treatment and was lost to follow-up. | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period I | Lost to Follow-up | 1 |
| Washout Period II | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 28.7 Years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 39 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 | 0 / 38 | 0 / 37 | 0 / 39 | 0 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 37 | 0 / 39 | 0 / 38 |
Outcome results
Primary
Area Under the Curve From Time 0 to t, AUC (0-t)
Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined from plasma concentration time profile of nicotine. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: Per protocol (PP) population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Lozenge (A) | Area Under the Curve From Time 0 to t, AUC (0-t) | 89.14 nanograms (ng)*hours (h)/milliliter (mL) | Standard Deviation 44.777 |
| Test Lozenge (B) | Area Under the Curve From Time 0 to t, AUC (0-t) | 87.38 nanograms (ng)*hours (h)/milliliter (mL) | Standard Deviation 42.816 |
| Test Lozenge (C) | Area Under the Curve From Time 0 to t, AUC (0-t) | 86.60 nanograms (ng)*hours (h)/milliliter (mL) | Standard Deviation 36.191 |
| Reference Lozenge | Area Under the Curve From Time 0 to t, AUC (0-t) | 91.97 nanograms (ng)*hours (h)/milliliter (mL) | Standard Deviation 45.601 |
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.93, 0.99]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.93, 0.99]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.91, 0.97]
Primary
Maximum Plasma Concentration (Cmax)
Maximum plasma nicotine concentration was determined from plasma-concentration time profiles. Cmax was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Lozenge (A) | Maximum Plasma Concentration (Cmax) | 18.50 ng/mL | Standard Deviation 5.626 |
| Test Lozenge (B) | Maximum Plasma Concentration (Cmax) | 18.39 ng/mL | Standard Deviation 5.099 |
| Test Lozenge (C) | Maximum Plasma Concentration (Cmax) | 17.41 ng/mL | Standard Deviation 4.796 |
| Reference Lozenge | Maximum Plasma Concentration (Cmax) | 18.97 ng/mL | Standard Deviation 6.001 |
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.93, 1.02]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.94, 1.03]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.88, 0.96]
Secondary
AUC(0-inf)
Area under the plasma nicotine concentration-time curve from zero extrapolated to infinity was determined. AUC(0-inf) was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Lozenge (A) | AUC(0-inf) | 100.33 ng*hr/mL | Standard Deviation 60.132 |
| Test Lozenge (B) | AUC(0-inf) | 98.90 ng*hr/mL | Standard Deviation 61.958 |
| Test Lozenge (C) | AUC(0-inf) | 97.83 ng*hr/mL | Standard Deviation 52.324 |
| Reference Lozenge | AUC(0-inf) | 104.53 ng*hr/mL | Standard Deviation 65.525 |
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.93, 0.99]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.93, 0.99]
Comparison: Null hypothesis considered no difference in the treatments being compared.90% CI: [0.9, 0.96]
Secondary
Plasma Half Life (t1/2)
Half-life of elimination of nicotine was determined. t1/2 was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Lozenge (A) | Plasma Half Life (t1/2) | 2.86 hours | Standard Deviation 0.8 |
| Test Lozenge (B) | Plasma Half Life (t1/2) | 2.91 hours | Standard Deviation 0.99 |
| Test Lozenge (C) | Plasma Half Life (t1/2) | 2.86 hours | Standard Deviation 1.07 |
| Reference Lozenge | Plasma Half Life (t1/2) | 2.94 hours | Standard Deviation 0.99 |
Secondary
Rate of Elimination (Kel)
Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Lozenge (A) | Rate of Elimination (Kel) | 0.26 1/ hour | Standard Deviation 0.06 |
| Test Lozenge (B) | Rate of Elimination (Kel) | 0.26 1/ hour | Standard Deviation 0.07 |
| Test Lozenge (C) | Rate of Elimination (Kel) | 0.27 1/ hour | Standard Deviation 0.11 |
| Reference Lozenge | Rate of Elimination (Kel) | 0.26 1/ hour | Standard Deviation 0.07 |
Secondary
Time to Maximum Plasma Concentration (Tmax)
Tmax was determined from plasma concentration time profiles. Tmax was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing
Population: PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Lozenge (A) | Time to Maximum Plasma Concentration (Tmax) | 1.50 hours |
| Test Lozenge (B) | Time to Maximum Plasma Concentration (Tmax) | 1.50 hours |
| Test Lozenge (C) | Time to Maximum Plasma Concentration (Tmax) | 1.50 hours |
| Reference Lozenge | Time to Maximum Plasma Concentration (Tmax) | 1.50 hours |
Comparison: Null hypothesis considered no difference in the treatments being compared.p-value: 0.220895% CI: [0, 0.5]Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis considered no difference in the treatments being compared.p-value: 0.569595% CI: [-0.25, 0.25]Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis considered no difference in the treatments being compared.p-value: 0.006395% CI: [0, 0.5]Wilcoxon (Mann-Whitney)