Trial Outcomes & Findings for Pharmacokinetics of Nicotine Film in Smokers (NCT NCT02239770)

Last Updated: 2018-08-31

Results Overview

In Phase 1, a trained nurse will implant an intravenous (IV) indwelling catheter in each participant. Participants will place a film containing zero, 2, or 4 mg of nicotine in their mouths and blood will be drawn every 10 minutes thereafter for the next 60 minutes, and then every 30 minutes for the next 2 hours (11 blood draws in all over 3 hours after using the nicotine film). In Phase 2, all 12 participants will receive an IV catheter and randomly allocated to consume 4 films over 12 hours in each of the following orders (a) 0,0,0,0 mg (b) 2,2,2,2 or (c) 4,4,0,4. A blood sample will be drawn at baseline prior to each film administration, and then at 30, 45, 60 and 120 minutes after each film administration and when the film is reported dissolved (20 blood draws in total).

Recruitment status

COMPLETED

Study phase

Target enrollment

24 participants

Primary outcome timeframe

10 min - 12 hours

Results posted on

2018-08-31

Participant Flow

In-person screening procedures included a review of medications and medical history, an assessment of drug use, a blood pressure measurement, a urine pregnancy test (if applicable), and an exhaled CO measurement to confirm prior 16 hour smoking abstinence. Those who did not satisfy inclusion criteria were excluded prior to randomization.

Participant milestones

Participant milestones
Measure	0 mg Nicotine Film In Part 1, 4 participants were allocated to this arm and received one placebo nicotine film. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2 mg Nicotine Film In Part 1, 4 participants were allocated to this arm and received one 2mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4 mg Nicotine Film In Part 1, 4 participants were allocated to this arm and received one 4mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	0, 0, 0, 0mg Nicotine Film Regimen In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 0, 0, 0, 0 mg. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2, 2, 2, 2mg Nicotine Film Regimen In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 2, 2, 2, 2 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4, 4, 0, 4mg Nicotine Film Regimen In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 4, 4, 0, 4 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.
Part 1 STARTED	4	4	4	0	0	0
Part 1 COMPLETED	4	4	4	0	0	0
Part 1 NOT COMPLETED	0	0	0	0	0	0
Part 2 STARTED	0	0	0	4	4	4
Part 2 COMPLETED	0	0	0	4	4	4
Part 2 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Nicotine Film in Smokers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	0 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one placebo nicotine film. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 2 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 4 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	0, 0, 0, 0mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 0, 0, 0, 0 mg. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2, 2, 2, 2mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 2, 2, 2, 2 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4, 4, 0, 4mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 4, 4, 0, 4 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	Total n=24 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 11.8 • n=5 Participants	40.8 years STANDARD_DEVIATION 13.6 • n=7 Participants	31.8 years STANDARD_DEVIATION 11.0 • n=5 Participants	44.8 years STANDARD_DEVIATION 6.5 • n=4 Participants	36.0 years STANDARD_DEVIATION 12.3 • n=21 Participants	37.5 years STANDARD_DEVIATION 14.7 • n=10 Participants	38.0 years STANDARD_DEVIATION 11.3 • n=115 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	10 Participants n=115 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	14 Participants n=115 Participants
Race/Ethnicity, Customized Race · Caucasian/white	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	17 Participants n=115 Participants
Race/Ethnicity, Customized Race · African American/black	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	5 Participants n=115 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Region of Enrollment United States	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=10 Participants	24 Participants n=115 Participants
Less than a college degree	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants	15 Participants n=115 Participants
Cigarettes smoked per day	20 cigarettes per day STANDARD_DEVIATION 8.0 • n=5 Participants	20 cigarettes per day STANDARD_DEVIATION 0.0 • n=7 Participants	14 cigarettes per day STANDARD_DEVIATION 3.0 • n=5 Participants	18.8 cigarettes per day STANDARD_DEVIATION 5.1 • n=4 Participants	18.5 cigarettes per day STANDARD_DEVIATION 8.6 • n=21 Participants	14.8 cigarettes per day STANDARD_DEVIATION 6.3 • n=10 Participants	17.7 cigarettes per day STANDARD_DEVIATION 5.8 • n=115 Participants
BMI	28.7 kg/m^2 STANDARD_DEVIATION 6.4 • n=5 Participants	30.1 kg/m^2 STANDARD_DEVIATION 10.0 • n=7 Participants	27.2 kg/m^2 STANDARD_DEVIATION 2.1 • n=5 Participants	28.7 kg/m^2 STANDARD_DEVIATION 3.5 • n=4 Participants	26.9 kg/m^2 STANDARD_DEVIATION 4.2 • n=21 Participants	27.4 kg/m^2 STANDARD_DEVIATION 5.3 • n=10 Participants	28.2 kg/m^2 STANDARD_DEVIATION 5.3 • n=115 Participants
Exhaled carbon monoxide	5.0 parts per million STANDARD_DEVIATION 3.0 • n=5 Participants	6.0 parts per million STANDARD_DEVIATION 2.0 • n=7 Participants	4.0 parts per million STANDARD_DEVIATION 3.0 • n=5 Participants	7.0 parts per million STANDARD_DEVIATION 2.2 • n=4 Participants	6.3 parts per million STANDARD_DEVIATION 3.3 • n=21 Participants	5.8 parts per million STANDARD_DEVIATION 3.2 • n=10 Participants	5.6 parts per million STANDARD_DEVIATION 2.8 • n=115 Participants
Penn State Cigarette Dependence Index Total Score	14 units on a scale STANDARD_DEVIATION 3.0 • n=5 Participants	12 units on a scale STANDARD_DEVIATION 1.0 • n=7 Participants	11 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants	11.8 units on a scale STANDARD_DEVIATION 2.9 • n=4 Participants	10.8 units on a scale STANDARD_DEVIATION 3.8 • n=21 Participants	11.0 units on a scale STANDARD_DEVIATION 2.2 • n=10 Participants	11.6 units on a scale STANDARD_DEVIATION 2.6 • n=115 Participants

PRIMARY outcome

Timeframe: 10 min - 12 hours

Population: Because the placebo nicotine film does not deliver any nicotine to the blood, peak plasma nicotine levels cannot be observed in the 0 mg Nicotine Film arm (Part 1) and 0, 0, 0, 0 mg Nicotine Film Regimen (Part 2).

Outcome measures

Outcome measures
Measure	0 mg Nicotine Film In Part 1, 4 participants were allocated to this arm and received one placebo nicotine film. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 2 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 4 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	0, 0, 0, 0mg Nicotine Film Regimen In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 0, 0, 0, 0 mg. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2, 2, 2, 2mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 2, 2, 2, 2 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4, 4, 0, 4mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 4, 4, 0, 4 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.
Peak Plasma Nicotine Concentrations Following Ingestion of a Single (Phase 1) or Repeated (Phase 2) Doses of Nicotine Film	—	5.78 ng/mL Interval 3.7 to 8.2	20.5 ng/mL Interval 15.9 to 31.0	—	8.71 ng/mL Interval 5.25 to 15.5	8.80 ng/mL Interval 3.96 to 14.86

SECONDARY outcome

Timeframe: Part 1: The QSU-Brief was measured at baseline and at 15, 35, 55, 80, 140, and 200 minutes post film administration. Part 2: The QSU-Brief was measured at baseline and at 50, 110, 230, 290, 410, 470, 590, and 690 minutes post FIRST film administration.

Population: This was a two part study. Participants in Part 1 and Part 2 were not assessed on the QSU-Brief measure at the same time intervals due to the differing study visit structures.

The Questionnaire of Smoking Urges-Brief (QSU-Brief) with a possible total score range of 10 to 70 was used to measure cigarette craving at baseline and at several points throughout the study visit for each participant. A score of 10 on this scale indicates very low cigarette craving, while a score of 70 indicates very high cigarette craving. Part 1: The QSU-Brief was measured at baseline and at 15, 35, 55, 80, 140, and 200 minutes post film administration. Part 2: The QSU-Brief was measured at baseline and at 50, 110, 230, 290, 410, 470, 590, and 690 minutes post FIRST film administration.

Outcome measures

Outcome measures
Measure	0 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one placebo nicotine film. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 2 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4 mg Nicotine Film n=4 Participants In Part 1, 4 participants were allocated to this arm and received one 4 mg nicotine film. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	0, 0, 0, 0mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 0, 0, 0, 0 mg. Placebo Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	2, 2, 2, 2mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 2, 2, 2, 2 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.	4, 4, 0, 4mg Nicotine Film Regimen n=4 Participants In Part 2, 4 participants were allocated to this arm and received one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 4, 4, 0, 4 mg. Nicotine Film: Nicotine orally dissolving films (ODF) are films containing nicotine (0, 2, or 4 mg). The active pharmaceutical ingredient in Nicotine ODF is nicotine polacrilex (20%, USP). The film used in Nicotine ODF has a muco-adhesive property, i.e. it can adhere to the oral mucosa and allow the drug to be absorbed through oral mucosa. After placement in the oral cavity, nicotine ODF dissolves over a 5-10 minute period.The unit-dose dosage is in the form of 1 in x 1 in square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 590 minutes	—	—	—	29.8 score on a scale Standard Deviation 14.4	36.0 score on a scale Standard Deviation 27.1	23.5 score on a scale Standard Deviation 18.4
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 690 minutes	—	—	—	30.3 score on a scale Standard Deviation 16.6	31.5 score on a scale Standard Deviation 20.9	26.8 score on a scale Standard Deviation 18.8
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 200 minutes	37.3 score on a scale Standard Deviation 25.4	18.3 score on a scale Standard Deviation 6.4	26.0 score on a scale Standard Deviation 13.3	—	—	—
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 230 minutes	—	—	—	35.5 score on a scale Standard Deviation 11.4	32.0 score on a scale Standard Deviation 21.4	24.0 score on a scale Standard Deviation 13.0
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 290 minutes	—	—	—	42.3 score on a scale Standard Deviation 11.3	34.5 score on a scale Standard Deviation 23.9	28.0 score on a scale Standard Deviation 20.6
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 410 minutes	—	—	—	36.0 score on a scale Standard Deviation 18.0	29.0 score on a scale Standard Deviation 19.7	28.5 score on a scale Standard Deviation 14.1
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 470 minutes	—	—	—	32.8 score on a scale Standard Deviation 17.2	29.3 score on a scale Standard Deviation 18.9	31.3 score on a scale Standard Deviation 18.2
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 0 minute	56.3 score on a scale Standard Deviation 8.4	35.0 score on a scale Standard Deviation 16.4	46.0 score on a scale Standard Deviation 8.3	51.8 score on a scale Standard Deviation 19.3	46.3 score on a scale Standard Deviation 23.0	39.3 score on a scale Standard Deviation 15.6
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 15 minutes	43.3 score on a scale Standard Deviation 14.2	22.8 score on a scale Standard Deviation 8.5	26.5 score on a scale Standard Deviation 7.1	—	—	—
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 35 minutes	35.0 score on a scale Standard Deviation 10.8	23.8 score on a scale Standard Deviation 12	22.5 score on a scale Standard Deviation 9.9	—	—	—
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 50 minutes	—	—	—	40.5 score on a scale Standard Deviation 15.9	30.8 score on a scale Standard Deviation 15.4	25.5 score on a scale Standard Deviation 15.6
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 55 minutes	29.8 score on a scale Standard Deviation 14.7	18.0 score on a scale Standard Deviation 5.7	19.0 score on a scale Standard Deviation 9.2	—	—	—
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 80 minutes	31.5 score on a scale Standard Deviation 16.8	16.8 score on a scale Standard Deviation 4.8	24.3 score on a scale Standard Deviation 9.7	—	—	—
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 110 minutes	—	—	—	39.5 score on a scale Standard Deviation 3.8	31.5 score on a scale Standard Deviation 16.0	27.0 score on a scale Standard Deviation 15.6
Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group 140 minutes	36.0 score on a scale Standard Deviation 19.4	16.5 score on a scale Standard Deviation 3.9	22.0 score on a scale Standard Deviation 10.4	—	—	—

SECONDARY outcome

Timeframe: Part 1: Systolic blood pressure was measured at baseline and at every 30 minutes, up to 180 minutes post film administration. Part 2: Systolic blood pressure was measured at baseline and at every 30 minutes, up to 660 minutes post film administration.

Population: Participants in Part 1 of the study were not assessed past 180 minutes post film administration, as this was the extent of the study visit.

Systolic blood pressure was measured using an electronic sphygmomanometer just prior to film administration and at every 30 minutes after film administration for the duration of each study visit.