Trial Outcomes & Findings for A Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers (NCT NCT01702519)

NCT ID: NCT01702519

Last Updated: 2015-03-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Baseline to 32 hours

Results posted on

2015-03-20

Participant Flow

Participants were recruited at a single clinical site in the US.

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.

Participant milestones

Participant milestones
Measure
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.
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.
Period 1
STARTED
20
20
Period 1
COMPLETED
20
20
Period 1
NOT COMPLETED
0
0
Washout Period
STARTED
20
20
Washout Period
COMPLETED
19
18
Washout Period
NOT COMPLETED
1
2
Period 2
STARTED
19
18
Period 2
COMPLETED
19
18
Period 2
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
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.
Washout Period
Lost to Follow-up
1
0
Washout Period
Withdrawal by Subject
0
2

Baseline Characteristics

A Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Test Then Reference Patch
n=20 Participants
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.
Reference Then Test Patch
n=20 Participants
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.
Total
n=40 Participants
Total of all reporting groups
Age, Continuous
36.3 Years
STANDARD_DEVIATION 11.33 • n=5 Participants
31.4 Years
STANDARD_DEVIATION 11.59 • n=7 Participants
33.8 Years
STANDARD_DEVIATION 11.58 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Sex: Female, Male
Male
14 Participants
n=5 Participants
14 Participants
n=7 Participants
28 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
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 • Interval 0.92 to 1.0
528.43 nanogram (ng)*hour (hr)/milliliter (mL)
Standard Deviation 129.762 • Interval 0.91 to 0.98

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
Maximum Measured Plasma Concentration (Cmax)
22.31 ng/mL
Standard Deviation 4.986
23.50 ng/mL
Standard Deviation 5.917

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)
505.13 ng*h/mL
Standard Deviation 118.939
541.15 ng*h/mL
Standard Deviation 134.854

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
Time to Maximum Plasma Concentration (Tmax)
10.00 hrs
Interval 0.5 to 24.0
17.99 hrs
Interval 2.0 to 24.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
Plasma Half-life (t1/2)
2.55 Hrs
Interval 2.0 to 3.5
2.59 Hrs
Interval 2.0 to 3.7

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Test Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.
Reference Patch
n=38 Participants
Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.
Rate of Elimination (Kel)
0.27 1/hr
Interval 0.2 to 0.3
0.27 1/hr
Interval 0.2 to 0.3

Adverse Events

Test Patch

Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths

Reference Patch

Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Test Patch
n=38 participants at risk
Participants were instructed to wear transdermal nicotine patch with test adhesive, for 24 hours.
Reference Patch
n=39 participants at risk
Participants were instructed to wear transdermal nicotine patch with reference adhesive, for 24 hours
General disorders
Application Site Erythema
39.5%
15/38 • Number of events 15 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
51.3%
20/39 • Number of events 20 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
General disorders
Application Site Pruritus
13.2%
5/38 • Number of events 5 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
17.9%
7/39 • Number of events 7 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
Nervous system disorders
Headache
5.3%
2/38 • Number of events 2 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
10.3%
4/39 • Number of events 4 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
Psychiatric disorders
Abnormal Dreams
0.00%
0/38 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments
10.3%
4/39 • Number of events 4 • AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER