Smoking
Conditions
Brief summary
Bioequivalence study to confirm that a NTS with a polyisobutylene (PIB) adhesive from an alternative supplier delivers the same nicotine blood profile as that of the currently approved NTS with a polyisobutylene adhesive from the current supplier.
Interventions
DRUGnicotine
nicotine transdermal patch
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 19-27 kg/m2 * smokes \>10 cigarettes per day for preceeding 6 months
Exclusion criteria
* inability to stop smoking during study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data. |
| Maximum Measured Plasma Concentration (Cmax) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data. |
| Time to Maximum Plasma Concentration (Tmax) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data. |
| Plasma Half-life (t1/2) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data |
| Rate of Elimination (Kel) | Baseline to 32 hours | Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at a single clinical site in the US.
Pre-assignment details
A total of 128 participants were screened, of which only 40 were randomized into the study. 71 participants did not meet the study eligibility criteria, 4 were lost to follow up, 6 withdrew consent while the remaining 7 were not randomized due to the other reason.
Participants by arm
| Arm | Count |
|---|---|
| Test Then Reference Patch Participants first applied a test nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied reference nicotine patch containing Reference adhesive (21 mg) for additional 24 hours. | 20 |
| Reference Then Test Patch Participants first applied the Reference nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied the Test nicotine patch containing reference adhesive (21 mg) for additional 24 hours. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period | Lost to Follow-up | 1 | 0 |
| Washout Period | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Test Then Reference Patch | Reference Then Test Patch | Total |
|---|---|---|---|
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 11.33 | 31.4 Years STANDARD_DEVIATION 11.59 | 33.8 Years STANDARD_DEVIATION 11.58 |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 38 | 26 / 39 |
| serious Total, serious adverse events | 0 / 38 | 0 / 39 |
Outcome results
Primary
Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Baseline to 32 hours
Population: Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Patch | Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t) | 494.54 nanogram (ng)*hour (hr)/milliliter (mL) | Standard Deviation 115.075 |
| Reference Patch | Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t) | 528.43 nanogram (ng)*hour (hr)/milliliter (mL) | Standard Deviation 129.762 |
Comparison: Null hypothesis considered no difference between the two treatments.90% CI: [0.912, 0.982]Treatment Ratio
Primary
Maximum Measured Plasma Concentration (Cmax)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Baseline to 32 hours
Population: Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Patch | Maximum Measured Plasma Concentration (Cmax) | 22.31 ng/mL | Standard Deviation 4.986 |
| Reference Patch | Maximum Measured Plasma Concentration (Cmax) | 23.50 ng/mL | Standard Deviation 5.917 |
Comparison: Null hypothesis considered no difference between the treatments.90% CI: [0.92, 1]Treatment Ratio
Secondary
Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Baseline to 32 hours
Population: Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Patch | Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf) | 505.13 ng*h/mL | Standard Deviation 118.939 |
| Reference Patch | Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf) | 541.15 ng*h/mL | Standard Deviation 134.854 |
Secondary
Plasma Half-life (t1/2)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data
Time frame: Baseline to 32 hours
Population: Per-prorocol population, which included all randomized participants who received at least one dose of the study treatment, had no protocol violation, and whose data was considered evaluable by the pharmacokineticist.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Patch | Plasma Half-life (t1/2) | 2.55 Hrs |
| Reference Patch | Plasma Half-life (t1/2) | 2.59 Hrs |
Secondary
Rate of Elimination (Kel)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Baseline to 32 hours
Population: Per protocol population, which included all randomized participants who took at least one dose of the study medications, had no protocol violations, and whose data was considered evaluable by the pharmacokineticist.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Patch | Rate of Elimination (Kel) | 0.27 1/hr |
| Reference Patch | Rate of Elimination (Kel) | 0.27 1/hr |
Secondary
Time to Maximum Plasma Concentration (Tmax)
Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data.
Time frame: Baseline to 32 hours
Population: Per protocol population, which included all randomized participants who took at least one dose of the drug, did not have any protocol deviations and whose data was considered evaluable by the pharmacokineticist.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Patch | Time to Maximum Plasma Concentration (Tmax) | 10.00 hrs |
| Reference Patch | Time to Maximum Plasma Concentration (Tmax) | 17.99 hrs |