Pharmacokinetics of Nicotine Film in Smokers

NCT02239770 | Completed Results

• 1 other identifier: 00000873
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking Cessation

Keywords

Nicotine; Random Delivery; Smoking Cessation; Plasma Nicotine; Oral Film

Outcome Measures

Primary Outcomes (1)

• Peak Plasma Nicotine Concentrations Following Ingestion of a Single (Phase 1) or Repeated (Phase 2) Doses of Nicotine Film

  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).

  10 min - 12 hours

Secondary Outcomes (2)

• Questionnaire of Smoking Urges-Brief Mean Total Score by Dose Group

  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.

• Mean Systolic Blood Pressure

  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.

Study Arms (6)

0 mg Nicotine Film

PLACEBO COMPARATOR

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

Drug: Placebo Nicotine Film

2 mg Nicotine Film

EXPERIMENTAL

In Part 1, 4 participants will be allocated to this arm and receive one 2 mg nicotine film.

Drug: Nicotine Film

4 mg Nicotine Film

EXPERIMENTAL

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

Drug: Nicotine Film

0, 0, 0, 0mg Nicotine Film Regimen

PLACEBO COMPARATOR

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.

Drug: Placebo Nicotine Film

2, 2, 2, 2mg Nicotine Film Regimen

EXPERIMENTAL

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.

Drug: Nicotine Film

4, 4, 0, 4mg Nicotine Film Regimen

EXPERIMENTAL

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.

Drug: Nicotine Film

Interventions

Nicotine Film 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; 2, 2, 2, 2mg Nicotine Film Regimen; 4 mg Nicotine Film; 4, 4, 0, 4mg Nicotine Film Regimen

Placebo Nicotine Film 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 mg Nicotine Film; 0, 0, 0, 0mg Nicotine Film Regimen

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 - 55
• Smoke \>9 cigarettes/day for at least the past 12 months
• Able to understand and consent to study procedures
• Able to read and write in English
• Exhaled Carbon Monoxide \<12 ppm at in-person screening

You may not qualify if:

• 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.
• 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.
• 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.
• Use of non-cigarette nicotine delivery product in the prior week (including cigars, pipes, chew, snus, hookah, electronic cigarette and marijuana mixed with tobacco).
• Use of an FDA approved cessation medication in past week (any NRT, Chantix, Wellbutrin)
• 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.
• Uncontrolled serious psychiatric illness or inpatient treatment in the past 6 months.
• Unwillingness to provide blood samples or history of repeatedly fainting during blood draws
• Any previous adverse reaction to NRT.
• 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.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

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

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Smoking Cessation

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Results Point of Contact

• Title: Dr. Patricia Sue Grigson
• Organization: Penn State College of Medicine

psg6@psu.edu

717-531-5772

Study Officials

• Patricia S. Grigson, Ph.D.

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

• Jonathan A Foulds, Ph.D.

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

• Christopher N Sciamanna, MD, MPH

  Penn State College of Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 15, 2014
• Study Start: September 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: August 31, 2018
• Results First Posted: August 31, 2018

Record last verified: 2018-08

Locations

US (1)