Pharmacokinetics of Nicotine Film in Smokers

NCT ID: NCT02239770

Last Updated: 2018-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-10-31

Brief 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.

Conditions

Smoking Cessation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

0 mg Nicotine Film

In Part 1, 4 participants will be allocated to this arm and receive one placebo nicotine film.

Group Type: PLACEBO_COMPARATOR

Placebo Nicotine Film

Intervention Type: DRUG

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 will be allocated to this arm and receive one 2 mg nicotine film.

Group Type: EXPERIMENTAL

Nicotine Film

Intervention Type: DRUG

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 will be allocated to this arm and receive one 4 mg nicotine film.

Group Type: EXPERIMENTAL

Nicotine Film

Intervention Type: DRUG

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 will be allocated to this arm and receive one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 0, 0, 0, 0 mg.

Group Type: PLACEBO_COMPARATOR

Placebo Nicotine Film

Intervention Type: DRUG

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 will be allocated to this arm and receive one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 2, 2, 2, 2 mg.

Group Type: EXPERIMENTAL

Nicotine Film

Intervention Type: DRUG

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 will be allocated to this arm and receive one nicotine film every 3 hours (for a total of 4 films over 12 hours) in the following order: 4, 4, 0, 4 mg.

Group Type: EXPERIMENTAL

Nicotine Film

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Aged 18 - 55

2. Smoke >9 cigarettes/day for at least the past 12 months

3. Able to understand and consent to study procedures

4. Able to read and write in English

5. Exhaled Carbon Monoxide <12 ppm at in-person screening

Exclusion Criteria

1. Unstable or significant medical conditions and conditions such as elevated blood pressure (Systolic >140 mm Hg or diastolic >90mm Hg at baseline), COPD and those that are likely to affect biomarker data such as kidney or liver disease.

2. Individuals with sodium-restricted diet, heart disease, recent heart attack, irregular heartbeat, stomach ulcers, or diabetes as well as those taking prescription medications for depression or asthma as indicated under "Warnings" section on FDA approved NRT Drug Facts Label.

3. More than weekly use in the past 3 months of illegal drugs or prescription drugs that are not being used for medically prescribed purposes or inpatient treatment for these in the past 6 months.

4. Use of non-cigarette nicotine delivery product in the prior week (including cigars, pipes, chew, snus, hookah, electronic cigarette and marijuana mixed with tobacco).

5. Use of an FDA approved cessation medication in past week (any NRT, Chantix, Wellbutrin)

6. Women who are pregnant (verified by urine pregnancy test at visit), trying to become pregnant (not using a medically acceptable form of birth control for at least one month prior to visit i.e., oral contraceptives, intrauterine device, double barrier), or nursing.

7. Uncontrolled serious psychiatric illness or inpatient treatment in the past 6 months.

8. Unwillingness to provide blood samples or history of repeatedly fainting during blood draws

9. Any previous adverse reaction to NRT.

10. Any other condition, serious illness, or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Patricia Sue Grigson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patricia S. Grigson, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Penn State College of Medicine

Jonathan A Foulds, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Penn State College of Medicine

Christopher N Sciamanna, MD, MPH

Role: STUDY_DIRECTOR

Penn State College of Medicine

Locations

Penn State College of Medicine/Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

00000873

Identifier Type: -

Identifier Source: org_study_id