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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prototype 1 | Experimental | 4mg nicotine lozenge administered orally as a single dose treatment per subject |
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| Prototype 2 | Experimental | 4mg nicotine lozenge administered orally as a single dose treatment per subject |
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| Prototype 3 | Experimental | 4mg nicotine lozenge administered orally as a single dose treatment per subject |
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| Reference Therapy | Active Comparator | 4mg nicotine lozenge (internationally marketed) to be administered orally as a single dose treatment per subject. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nicotine | Drug | 4 mg nicotine lozenge experimental |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 Concentration (Cmax) | Maximum plasma nicotine concentration was determined from plasma-concentration time profiles. Cmax was based on the baseline adjusted nicotine plasma concentration data. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
- smoked commercially-manufactured cigarettes daily for the preceding 12 months and routinely smokes first cigarette within 30mins of awakening.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lambda Therapeutic Research Ltd | Ahmedabad | Gujarat | 380 061 | India |
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 were recruited at the clinical site.
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| ID | Title | Description |
|---|---|---|
| FG000 | Total Participants |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period I |
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| Washout Period I |
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| Period II |
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| Washout Period II |
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| Washout Period III |
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| Period III |
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| Period IV |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| 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 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. | Per protocol (PP) population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Mean | Standard Deviation | nanograms (ng)*hours (h)/milliliter (mL) | 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 |
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Adverse events were collected from the start of the treatment, and until 7 days following administration of the last dose of 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 | Test Lozenge (A) | 4 mg nicotine lozenge with excipient A, was administered orally as a single dose treatment. |
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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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| 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. |
| 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 |
| Rate of Elimination (Kel) | Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data. | 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 |
| 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. | 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 |
|
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Test Lozenge (B) |
4 mg nicotine lozenge with excipient B, was administered orally as a single dose treatment. |
| OG002 | Test Lozenge (C) | 4 mg nicotine lozenge with excipient C, was administered orally as a single dose treatment. |
| OG003 | Reference Lozenge | Reference 4 mg nicotine lozenge, was administered orally as a single dose treatment. |
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| 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. | PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| 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. | PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Mean | Standard Deviation | ng*hr/mL | 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 |
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| 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. | PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Median | Full Range | hours | 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 |
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| Secondary | Rate of Elimination (Kel) | Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data. | PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Mean | Standard Deviation | 1/ hour | 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 |
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| 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. | PP population: all randomized participants profiles, without a protocol deviation that would have lead to the data exclusion. | Posted | Mean | Standard Deviation | hours | 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 |
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| 0 |
| 38 |
| 0 |
| 38 |
| EG001 | Test Lozenge (B) | 4 mg nicotine lozenge with excipient B, was administered orally as a single dose treatment. | 0 | 37 | 0 | 37 |
| EG002 | Test Lozenge (C) | 4 mg nicotine lozenge with excipient C, was administered orally as a single dose treatment. | 0 | 39 | 0 | 39 |
| EG003 | Reference Lozenge | Reference 4 mg nicotine lozenge, was administered orally as a single dose treatment. | 0 | 38 | 0 | 38 |
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 |
| Treatment Ratio |
| 0.99 |
| 2-Sided |
| 90 |
| 0.94 |
| 1.03 |
| Yes |
| Non-Inferiority or Equivalence |
Testing Bioequivalence |
| Null hypothesis considered no difference in the treatments being compared. | Treatment Ratio | 0.92 | 2-Sided | 90 | 0.88 | 0.96 | Yes | Non-Inferiority or Equivalence | Testing Bioequivalence |
| Treatment Ratio |
| 0.96 |
| 2-Sided |
| 90 |
| 0.93 |
| 0.99 |
| Yes |
| Non-Inferiority or Equivalence |
Testing bioequivalence |
| Null hypothesis considered no difference in the treatments being compared. | Treatment Ratio | 0.93 | 2-Sided | 90 | 0.90 | 0.96 | Yes | Non-Inferiority or Equivalence | Testing bioequivalence |
Null hypothesis considered no difference in the treatments being compared.
| Wilcoxon (Mann-Whitney) |
| 0.5695 |
| Median Difference (Final Values) |
| 0.00 |
| 2-Sided |
| 95 |
| -0.25 |
| 0.25 |
Based on Hodges Lehmann estimate |
| No |
| Superiority or Other |
| Null hypothesis considered no difference in the treatments being compared. | Wilcoxon (Mann-Whitney) | 0.0063 | Median Difference (Final Values) | 0.00 | 2-Sided | 95 | 0.00 | 0.50 | Based on Hodges Lehmann estimate | No | Superiority or Other |