Pharmacokinetics of Nicotine Film in Smokers
Condition: Smoking Cessation
Study type: Interventional

Summary: 
      The objective of this study is to test the effect of a range of doses of a novel nicotine
      film on plasma nicotine levels, expired carbon monoxide and, via a questionnaire, subjective
      ratings of the film and side effects. The nicotine film is not part of standard of care and
      is not available in a non-investigational setting. The investigators hypothesize that plasma
      nicotine levels will be in keeping with those induced by other oral nicotine replacement
      therapies (NRTs) and by the smoking of a cigarette. Thus, the investigators predict that
      random delivery of nicotine via the oral film will be safe and well-tolerated by the human
      subjects.
    

Detailed description: 
      Briefly, this will be a two-part pharmacokinetic study, each part involving 12 participants.

      In Part 1, 4 volunteer smokers (both male, and female) each will each abstain from all
      tobacco/nicotine products for 16 hours before attending the Penn State Clinical Research
      Center for the measurement of the blood nicotine pharmacokinetic response to a randomly
      allocated dose of either (a) 0mg, (b) 2mg or (c) 4mg oral nicotine film. A trained nurse will
      implant an intravenous indwelling catheter in each participant, through which they will
      provide a baseline blood sample after 16 hours of abstinence, confirmed by an exhaled
      carbon-monoxide < 6 ppm, and then will place a nicotine film in their mouth and have blood
      drawn every 10 minutes for the next 60 minutes, and then every 30 minutes for the next 2
      hours plus one blood draw one minute after the film dissolves (11 blood draws in all over 3
      hours after using the nicotine film). Subjective measures of (a) nicotine withdrawal and
      craving and (b) potential nicotine effects, including symptoms of nicotine intoxication, will
      be recorded at scheduled intervals through the study visit, and blood pressure and heart rate
      will be measured every 30 minutes. The investigators expect to find peak blood nicotine
      concentrations of around 3-4 ng/ml and 5-6 ng/ml from each of the two active doses of
      nicotine film, with the peak occurring approximately 30 minutes after film administration,
      and the level having dropped by at least half by 2 hours later. These peak blood nicotine
      levels are all within the range that a smoker might obtain after smoking a single cigarette.
      Upon completion of all blood draws, a trained nurse will remove the catheter and treat the
      puncture wound. The participant will receive $120 for this visit.

      In Part 2, 12 participants will again attend the Penn State Clinical Research Center after 16
      hours of abstinence, confirmed by an exhaled carbon monoxide < 12 ppm. On this visit
      participants will consume repeated doses of nicotine films intended to mimic the patterns of
      delivery that will be used in smoking cessation study 2 and fMRI study 3. The primary issue
      here is to determine peak blood nicotine concentrations and safety resulting from (a) the
      highest dose schedule that could be used in study 2 and 3, (b) the steady state levels
      produced by repeated administration of the 2mg nicotine film, and (c) to compare the
      subjective effects to placebo. In order to mimic the most aggressive dosing schedule possible
      in the "random nicotine" arm of study 2 and 3, the investigators will assess blood nicotine,
      subjective and basic cardiovascular responses to consuming nicotine film every 3 hours
      beginning at 8:00 a.m. on the following schedule: 4mg, 4mg, 0mg, 4mg.

      All 12 participants will attend after 16 hours nicotine abstinence. 4 subjects each will be
      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, 60 and 120 minutes after each film administration as
      well as one minute after film dissolution (20 blood draws in total), with heart rate and BP
      being assessed every 30 minutes. Nicotine has a half-life of approximately 2 hours, so the
      investigators expect that with 3-hourly administration there will not be much build-up of
      nicotine levels and these levels will be on the low end of the typical levels experienced by
      smokers every day. The participants will each receive $240 for this visit.

      At clinic visits, in addition to providing blood samples for measurement of plasma nicotine
      concentration, participants will be asked to complete a battery of survey instruments
      assessing subjective effects (e.g. withdrawal and craving) and physical symptoms (e.g.
      dizziness and nausea) that could be caused by either nicotine withdrawal or nicotine
      exposure.
    

Intervention name(s): Nicotine Film; Placebo Nicotine Film
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Nicotine; Random Delivery; Smoking Cessation; Plasma Nicotine; Oral Film