Nicotine Pharmacokinetics From Research Electronic Nicotine Delivery System S-TA-U001 in Smokers and E-Cigarette Users

NCT02792426 | Completed Phase 1

• 2 other identifiers: NPK016-N44DA271201500019C-0-0-1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

To better understand the PK and associated pharmacodynamic (PD) responses produced by the Research ENDS S-TA-U001 product, this study will compare the Research ENDS S-TA-U001 to

• The subject's own brand combustion (non-menthol) cigarette and a U.S. FDA approved smoking cessation product, the NICORETTE Inhalator, in current non-menthol cigarette smokers who have some limited e-cigarette experience (Group 1).
• Commercially available products in current primarily e-cigarette users (experienced ENDS users) (Group 2) The PK/PD session for each product will be conducted in a controlled clinical setting with frequent PK sampling after 14 hours of supervised abstinence from all forms of nicotine. Subjects will familiarize themselves with the Research ENDS S-TA-U001 and NICORETTE Inhalator by using each product in the real world for one day before the PK/PD session for that product. Primary Objectives: Group 1 objectives are to characterize the nicotine PK profile (eg, maximum plasma concentration \[Cmax\], time to maximum plasma concentration \[Tmax\], area under the concentration-time curve \[AUC\], and terminal half-life \[t1/2\]) for 10 inhalation and ad lib sessions of Research ENDS S-TA-U001 and explore how the Cmax compares to a 15 ng/mL level during the 4.5-minute 10 inhalation and the 6 hour ad lib use sessions, to compare the PK profiles between Research ENDS S-TA-U001 to the profiles of combustion cigarettes measured at the baseline session, and to demonstrate superiority of PK profile of Research ENDS S-TA-U001 to that of the marketed NICORETTE Inhalator. Group 2 objectives are to characterize the nicotine PK profile of Research ENDS S-TA-U001 and explore how the Cmax compares to a 15 ng/mL level during the 4.5-minute 10 inhalation and 6 hour ad lib use sessions, and to compare the PK profile between Research ENDS S-TA-U001 to the profile of a commercial ENDS product measured at the baseline session. Secondary objectives: Secondary objectives include comparison of the nicotine PK of the Research ENDS S-TA-U001 to the subjects' normal nicotine source (combustion cigarettes for Group 1 or commercial ENDS for Group 2), to evaluate the safety and tolerability of Research ENDS S-TA-U001, to evaluate the effects on craving and user satisfaction of the Research ENDS S-TA-U001 vs a combustion cigarette or the NICORETTE Inhalator (Group 1) or a commercial ENDS product (Group 2), and to evaluate various biomarkers following use of each test product.

Conditions

Cigarette Smoking

Keywords

Smoking Cessation; Nicotine Dependence; Tobacco Dependence

Outcome Measures

Primary Outcomes (3)

• Nicotine Cmax

  Characterize nicotine Cmax of all test products during a 10-puff 4.5-minute session and a 6 hour ad lib use session and compare to a target level of 15 ng/mL

  ~5 minutes before administration and at 1, 3, 5, 7, 10, 15, 30, 60, 90, 120, 130, 140, 150, 180, 210, 240, 300, 360, 420, and 480 minutes from start of each administration

• Nicotine AUC

  Characterize nicotine AUC from time 0 to the last time point for all test products

  ~5 minutes before administration and at 1, 3, 5, 7, 10, 15, 30, 60, 90, 120, 130, 140, 150, 180, 210, 240, 300, 360, 420, and 480 minutes from start of each administration

• Nicotine tmax

  Characterize the time when the maximum nicotine concentration is reached for all test products during a 10-puff 4.5-minute session and a 6 hour ad lib use session

  ~5 minutes before administration and at 1, 3, 5, 7, 10, 15, 30, 60, 90, 120, 130, 140, 150, 180, 210, 240, 300, 360, 420, and 480 minutes from start of each administration

Secondary Outcomes (6)

• Adverse events and vital signs

  5 days

• Effects on craving

  5 days

• Effects on user satisfaction

  5 days

• White blood cell count

  5 days

• Carbon monoxide

  5 days

Study Arms (3)

Group 1 AB

ACTIVE COMPARATOR

Smoker subject's own brand of combustion cigarette

Drug: Research ENDS S-TA-U001; Drug: Nicorette Inhalator

Group 1 BA

ACTIVE COMPARATOR

Smoker subject's own brand of combustion cigarette

Drug: Research ENDS S-TA-U001; Drug: Nicorette Inhalator

Group 2

ACTIVE COMPARATOR

E-cigarette user's own brand of electronic nicotine delivery system (ENDS)

Drug: Research ENDS S-TA-U001

Interventions

Research ENDS S-TA-U001 DRUG

Group 1 AB; Group 1 BA; Group 2

Nicorette Inhalator DRUG

Group 1 AB; Group 1 BA

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Group 1: in order to participate in the study, potential subjects must:
• Be males and females of any race between 21 and 65 years of age inclusive
• Be current combustion cigarette smokers, defined as smoking a minimum of 10 combustion cigarettes per day for a period of at least 3 months, who smoke commercial (non menthol) cigarettes
• Not be currently planning to quit smoking combustion cigarettes in the next 3 months
• Have blood cotinine ≥100 ng/mL and carbon monoxide ≥10 ppm at Screening to confirm smoking status
• Weigh at least 45 kg and have a Body Mass Index (BMI) between 18 and 40 kg/m2, inclusive, at Screening
• Be healthy, in the Investigator's opinion, according to medical history; physical examination; electrocardiogram (ECG); and clinical chemistry, urine, and hematological laboratory tests
• Be willing to refrain from using any source of nicotine other than study supplies for the duration of the study confinement period
• Have vital signs as follows:
• Resting heart rate between 50 and 90 beats per minute
• Systolic blood pressure below 150 mm Hg
• Diastolic blood pressure below 90 mm Hg
• Have electrolytes (ie, Na, K, Cl, HCO3) and hematocrit that are clinically normal (± 10% of laboratory limits); subjects marginally outside of this range may be eligible at the discretion of the study physician
• Have liver function tests (ie, total bilirubin, ALT, AST, GGT, and alkaline phosphatase) less than three times the upper normal limit
• Have kidney function tests (ie, creatinine and BUN) within clinically normal limits (± 10% of laboratory limits) and calculated creatinine clearance \> 80 mL/min for females and \> 90 mL/min for males

You may not qualify if:

• For Group 1 and Group 2: in order to participate in the study, potential subjects must not:
• Have expected inability to comply with study protocol
• Have used any of the following in the past 30 days: ultra-light, hand or roll-your-own, menthol, or unfiltered combustion cigarettes; any other form of tobacco (eg, chews, dips, pipes, cigars, hookah); or any form of nicotine replacement therapy (eg, patch, gum, lozenge, inhaler, nasal spray).
• Be pregnant (based on serum test) or nursing (by self-report)
• Have history or diagnosis of airway disease, including adult onset asthma or chronic obstructive pulmonary disease (including emphysema or chronic bronchitis), use of an inhaler (apart from a nicotine inhaler) in the previous 5 years, or any episodes of wheezing or bronchospasm in the previous 5 years (history of resolved childhood asthma is acceptable)
• Have baseline spirometry values (FEV1, FVC, and FEV1/FVC) outside of the lower limit of normal as defined by Hankinson et al, Am J Respir Crit Care Med 1999; 159:179-187.
• Have had treatment with prescription medications within 21 days or over-the-counter medication within 24 hours of the planned first product use occasion, except for oral or hormonal contraceptive therapies.
• Have used any drugs or substances (except tobacco) known to be strong inducers or inhibitors of any CYP enzymes (formerly known as cytochrome P450 enzymes) within a 28 days period prior to first product administration. For a list of such drugs and substances, please refer to http://medicine.iupui.edu/clinpharm/ddis/main-table/.
• Have an active cough, recent or chronic, excluding "smoker's cough"
• Have any active respiratory infection
• Have a history of clinically significant cardiac, pulmonary, renal, hepatic, endocrine, neurological, gastrointestinal, metabolic, psychiatric, or hematologic disorders
• Have poor venous access as defined by being unable to draw samples through a catheter at the screening visit
• Have been hospitalized within 4 weeks before Screening
• Have received any other investigational treatment or Test Product within 30 days from randomization (or within 5 half-lives of the Test Product, if known, whichever is greater)
• Have a history of allergic, anaphylactic, or other hypersensitivity reaction to any e cigarette , or any of the components associated with these products such as propylene glycol

Sponsors & Collaborators

• NJOY, Inc.: lead
• LA Clinical Trials: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

LA Clinical Trials

Burbank, California, 91505, United States

Location

MeSH Terms

Conditions

Cigarette Smoking; Smoking Cessation; Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Tobacco Smoking; Smoking; Behavior; Tobacco Use; Health Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Mitchell Nides, PhD

  LA Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: June 7, 2016
• Study Start: October 5, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: May 17, 2018

Record last verified: 2018-05

Locations

US (1)