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Multiple-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product.

Multiple-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product. A Study in Healthy Smokers.

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01084707
Enrollment
40
Registered
2010-03-10
Start date
2009-01-31
Completion date
2009-04-30
Last updated
2012-07-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tobacco Dependence

Keywords

Smoking Cessation, Nicotine pharmacokinetics

Brief summary

A comparison of three products for oral nicotine replacement with respect to pharmacokinetics after multiple-doses of nicotine.

Detailed description

This study compares a new oral Nicotine Replacement Therapy (NRT) product with NiQuitin™ lozenge 4 mg and Nicorette®gum 4 mg, after 12 hours of nicotine abstinence, with respect to steady-state nicotine pharmacokinetics, during 12 hours after start of the first administration. Multiple doses of each treatment are given once hourly during five separate treatment visits scheduled in a crossover setting with randomized treatment sequences. The study will include 40 healthy smokers between 18-50 years, who have been smoking at least 20 cigarettes daily during at least one year preceding inclusion. Subjects and study personnel will be aware of which treatment is administered at a given visit.

Interventions

DRUGOral Nicotine

Oral Nicotine either self-administered or provided by study personnel within 12 hours

DRUGNicotine Lozenge

Nicotine lozenge marketed as NiQuitin™ 4 mg hourly within 12 hours

DRUGNicotine gum

Nicotine gum marketed as Nicorette® 4 mg hourly within 12 hours

Sponsors

McNeil AB
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No

Inclusion criteria

* Healthy smokers, smoking at least 20 cigarettes daily during at least one year preceding inclusion and BMI between 17.5 and 30.0 kg/m2. * Female participants of child-bearing potential are required to use a medically acceptable means of birth control. * A personally signed and dated informed consent document, indicating that the subject has been informed of all pertinent aspects of the study.

Exclusion criteria

* Pregnancy, lactation or intended pregnancy. * Treatment with an investigational product or donation or loss of blood within 3 month preceding the first dose of study medication. * Prior regular use of nicotine mouth spray

Design outcomes

Primary

MeasureTime frameDescription
Maximum Plasma ConcentrationDuring the last dosing interval (hour 11-12 post-dose)Cmax, which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered measured in nanograms/milliliter (ng/ml)
Average ConcentrationDuring the last dosing interval (hour 11-12 post-dose)Pharmacokinetic measurement - average concentration during the last dosing interval (AUCtau)

Secondary

MeasureTime frameDescription
Time of Maximum ConcentrationDuring the last dosing interval (hour 11-12 post-dose)The time at which maximum concentration is reached (Tmax)
Minimum Plasma ConcentrationDuring the last dosing interval (hour 11-12 post-dose)The minimum nicotine plasma concentration during the last dosing interval (Cmin)
Peak-Trough FluctuationDuring the last dosing interval (hour 11-12 post-dose)Percent of peak-trough fluctuation over one dosing interval at steady state (PTF)
Nicotine Plasma ConcentrationOne hour after start of treatmentThe nicotine concentration in plasma (area under the nicotine plasma concentration curve) 1 hour after start of treatment

Countries

Sweden

Participant flow

Recruitment details

This was a five-arm cross-over trial, with subjects randomized to the order they received the different treatments and with analysis performed on valid pharmacokinetic data. Therefore, Number of Participants Analyzed in each arm represents the same subjects, and the total is not consistent with numbers provided in the participant flow module.

Participants by arm

ArmCount
All Randomized Subjects
All subjects randomized into the trial, e.g., Full Analysis Set
40
Total40

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyWithdrawal by Subject6

Baseline characteristics

CharacteristicAll Randomized Subjects
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
40 Participants
Region of Enrollment
Sweden
40 participants
Sex: Female, Male
Female
18 Participants
Sex: Female, Male
Male
22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —
other
Total, other adverse events
29 / 4022 / 3727 / 3624 / 3518 / 35
serious
Total, serious adverse events
0 / 400 / 370 / 360 / 350 / 35

Outcome results

Primary

Average Concentration

Pharmacokinetic measurement - average concentration during the last dosing interval (AUCtau)

Time frame: During the last dosing interval (hour 11-12 post-dose)

Population: ITT

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Oral Nicotine 24-SAAverage Concentration13.33 (ng/ml)Standard Deviation 5.55
Oral Nicotine 24Average Concentration14.04 (ng/ml)Standard Deviation 4.5
Oral Nicotine 48Average Concentration27.50 (ng/ml)Standard Deviation 9.18
NiQuitin™ Lozenge 4 mgAverage Concentration23.70 (ng/ml)Standard Deviation 9.86
Nicorette® Gum 4 mgAverage Concentration22.15 (ng/ml)Standard Deviation 7.49
Primary

Maximum Plasma Concentration

Cmax, which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered measured in nanograms/milliliter (ng/ml)

Time frame: During the last dosing interval (hour 11-12 post-dose)

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Oral Nicotine 24-SAMaximum Plasma Concentration15.43 (ng/ml)Standard Deviation 6.12
Oral Nicotine 24Maximum Plasma Concentration16.49 (ng/ml)Standard Deviation 4.99
Oral Nicotine 48Maximum Plasma Concentration30.07 (ng/ml)Standard Deviation 9.77
NiQuitin™ Lozenge 4 mgMaximum Plasma Concentration27.07 (ng/ml)Standard Deviation 10.95
Nicorette® Gum 4 mgMaximum Plasma Concentration25.96 (ng/ml)Standard Deviation 8.55
Secondary

Minimum Plasma Concentration

The minimum nicotine plasma concentration during the last dosing interval (Cmin)

Time frame: During the last dosing interval (hour 11-12 post-dose)

Population: ITT

ArmMeasureValue (MEAN)Dispersion
Oral Nicotine 24-SAMinimum Plasma Concentration11.54 (ng/ml)Standard Deviation 4.71
Oral Nicotine 24Minimum Plasma Concentration11.67 (ng/ml)Standard Deviation 4.04
Oral Nicotine 48Minimum Plasma Concentration25.32 (ng/ml)Standard Deviation 8.41
NiQuitin™ Lozenge 4 mgMinimum Plasma Concentration22.14 (ng/ml)Standard Deviation 9.71
Nicorette® Gum 4 mgMinimum Plasma Concentration19.00 (ng/ml)Standard Deviation 7
Secondary

Nicotine Plasma Concentration

The nicotine concentration in plasma (area under the nicotine plasma concentration curve) 1 hour after start of treatment

Time frame: One hour after start of treatment

Population: ITT

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Oral Nicotine 24-SANicotine Plasma Concentration4.49 (ng/ml)Standard Deviation 1.6
Oral Nicotine 24Nicotine Plasma Concentration4.76 (ng/ml)Standard Deviation 1.45
Secondary

Peak-Trough Fluctuation

Percent of peak-trough fluctuation over one dosing interval at steady state (PTF)

Time frame: During the last dosing interval (hour 11-12 post-dose)

Population: ITT

ArmMeasureValue (MEAN)Dispersion
Oral Nicotine 24-SAPeak-Trough Fluctuation35.6 Percent FluctuationStandard Deviation 14.2
Oral Nicotine 24Peak-Trough Fluctuation38.4 Percent FluctuationStandard Deviation 14.9
Oral Nicotine 48Peak-Trough Fluctuation21.7 Percent FluctuationStandard Deviation 8.7
NiQuitin™ Lozenge 4 mgPeak-Trough Fluctuation29.1 Percent FluctuationStandard Deviation 10.7
Nicorette® Gum 4 mgPeak-Trough Fluctuation36.3 Percent FluctuationStandard Deviation 12.8
Secondary

Time of Maximum Concentration

The time at which maximum concentration is reached (Tmax)

Time frame: During the last dosing interval (hour 11-12 post-dose)

Population: ITT

ArmMeasureValue (MEDIAN)Dispersion
Oral Nicotine 24-SATime of Maximum Concentration15.0 (minutes)Full Range 9
Oral Nicotine 24Time of Maximum Concentration10.0 (minutes)Full Range 9.2
Oral Nicotine 48Time of Maximum Concentration10.0 (minutes)Full Range 5.3
NiQuitin™ Lozenge 4 mgTime of Maximum Concentration25.0 (minutes)Full Range 10.4
Nicorette® Gum 4 mgTime of Maximum Concentration30.0 (minutes)Full Range 9.1

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026