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To compare the bio equivalence of new nicotine lozenge formulation with the reference nicotine lozenge so as to deliver the same nicotine blood profile.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test nicotine lozenge (2 mg) | Experimental | 2 mg test nicotine lozenge to be chewed. |
|
| Test nicotine lozenge (4 mg) | Experimental | 4 mg test nicotine lozenge to be chewed. |
|
| Reference nicotine lozenge (2 mg) | Active Comparator | 2 mg reference nicotine lozenge to be chewed. |
|
| Reference nicotine lozenge (4 mg) | Active Comparator | 4 mg reference nicotine lozenge to be chewed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotine (2 mg) | Drug | 2 mg nicotine lozenge in two formulations |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| Maximum Observed Plasma Concentration [Cmaximum (Max)] | Cmax was depicted from plasma concentration of nicotine. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC [0-infinity (Inf)] | AUC (0-inf) was evaluated using the trapezoid rule. | 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 |
| Time to Reach Maximum Plasma Nicotine Concentration (Tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion NEBRASKA | Lincoln | Nebraska | 68502 | United States |
Out of 141 participants screened, only 50 were randomized since 91 were screen failures.
Participants were recruited at the clinical site.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2 Milligram (mg) Cherry Lozenge | Participants were instructed to move the 2mg Cherry mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. |
| FG001 | 2mg Mint Lozenge | Participants were instructed to move the 2mg Mint (peppermint) mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. |
| FG002 | 4mg Cherry Lozenge | Participants were instructed to move the 4mg Cherry mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. |
| FG003 | 4mg Mint Lozenge | Participants were instructed to move the 4mg Mint mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Washout Period 1 |
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| Period 2 |
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| Washout Period 2 |
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| Period 3 |
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| Washout Period 3 |
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| Period 4 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Randomized Participants | All randomized participants were evaluated for baseline measures |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Analysis was done per intention to treat (ITT) population. | Posted | Mean | Standard Deviation | nanogram (ng).hour (hr)/millilitre (mL) | 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 |
|
Adverse Events were collected from the starting time of the investigational product, and until 5 days following last administration of the investigational product.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2mg Cherry Lozenge | Participants were instructed to move the 2mg Cherry mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D016540 | Smoking Cessation |
| ID | Term |
|---|---|
| D015438 | Health Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D009538 | Nicotine |
| ID | Term |
|---|---|
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
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| Nicotine (4 mg) | Drug | 4 mg nicotine lozenge in two formulations |
|
Tmax was time at which Cmax of nicotine was reached. |
| 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 |
| Apparent Elimination Half-life of Nicotine T(1/2) | T(1/2) was calculated using plasma time-concentration values. | 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 |
| Elimination Rate Constant for Plasma Nicotine: K (el) | Kel was calculated with the help of plasma time concentration values. | 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 |
| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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|
| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
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| NOT COMPLETED |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants were instructed to move the 2mg Mint (peppermint) mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge
| OG002 | 4mg Cherry Lozenge | Participants were instructed to move the 4mg Cherry mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge |
| OG003 | 4mg Mint Lozenge | Participants were instructed to move the 4mg Mint (peppermint) mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge |
|
|
|
| Primary | Maximum Observed Plasma Concentration [Cmaximum (Max)] | Cmax was depicted from plasma concentration of nicotine. | Analysis was done per intention to treat (ITT) population. | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
|
| Secondary | AUC [0-infinity (Inf)] | AUC (0-inf) was evaluated using the trapezoid rule. | Analysis was done per intention to treat (ITT) population. | Posted | Mean | Standard Deviation | ng.hr/mL | 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 |
|
|
|
|
| Secondary | Time to Reach Maximum Plasma Nicotine Concentration (Tmax) | Tmax was time at which Cmax of nicotine was reached. | Analysis was done per intention to treat (ITT) population. | Posted | Median | Full Range | hr | 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 |
|
|
|
|
| Secondary | Apparent Elimination Half-life of Nicotine T(1/2) | T(1/2) was calculated using plasma time-concentration values. | Analysis was done per intention to treat (ITT) population. | Posted | Median | Full Range | hr | 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 |
|
|
|
|
| Secondary | Elimination Rate Constant for Plasma Nicotine: K (el) | Kel was calculated with the help of plasma time concentration values. | Analysis was done per intention to treat (ITT) population. | Posted | Median | Full Range | 1/hr | 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 |
|
|
|
|
| 0 |
| 47 |
| 6 |
| 47 |
| EG001 | 2mg Mint Lozenge | Participants were instructed to move the 2mg Mint (peppermint) mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge. | 0 | 46 | 9 | 46 |
| EG002 | 4mg Cherry Lozenge | Participants were instructed to move the 4mg Cherry mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge | 0 | 45 | 13 | 45 |
| EG003 | 4mg Mint Lozenge | Participants were instructed to move the 4mg Mint (peppermint) mini nicotine lozenge from one side of the mouth to the other periodically and not to swallow or chew the lozenge | 1 | 47 | 15 | 47 |
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| 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. | Wilcoxon Signed Rank Test | Geometric Mean Ratio | 0.97 | 2-Sided | 90 | 0.93 | 1.02 | Geometric mean ratio of Cherry and Mint lozenge was determined by exponentiating least-squares means of log-transformed value. | Yes | Non-Inferiority or Equivalence | Bio-equivalence between two dosage treatments was concluded if the 90% confidence interval for the ratio of the means for Cmax lies within the interval 0.80 to 1.25. |
| 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. | Wilcoxon Signed Rank Test | Geometric Mean Ratio | 1.02 | 2-Sided | 90 | 0.98 | 1.06 | Geometric mean ratio of Cherry and Mint lozenge was determined by exponentiating least-squares means of log-transformed value. | Yes | Non-Inferiority or Equivalence | Bio-equivalence between two dosage treatments was concluded if the 90% confidence interval for the ratio of the means for AUC (0-inf) lies within the interval 0.80 to 1.25. |
The null hypothesis considered that there is no median within-subject difference between two treatment groups. |
| Wilcoxon Signed Rank Test |
The value of Tmax was adjusted for this non-parametric analysis. |
| 0.6790 |
| Mean Difference (Final Values) |
| 0.0005 |
| 95 |
The median difference was calculated as Cherry minus Peppermint. |
| No |
| Superiority or Other |
|
The null hypothesis considered that there is no median within-subject difference between two treatment groups. |
| Wilcoxon Signed Rank Test |
The value of T (1/2) was adjusted for this non-parametric analysis. |
| 0.4523 |
| Mean Difference (Final Values) |
| 0.0538 |
| 95 |
The median difference was calculated as Cherry minus Peppermint. |
| No |
| Superiority or Other |
|
The null hypothesis considered that there is no median within-subject difference between two treatment groups. |
| Wilcoxon Signed Rank Test |
This non-parametric analysis was performed on the unadjusted values of parameters. |
| 0.5370 |
| Median Difference (Final Values) |
| -0.0042 |
| 95 |
The median difference was calculated as Cherry minus Peppermint. |
| No |
| Superiority or Other |