Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

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
Have an ECG performed that demonstrates normal sinus rhythm, normal conductivity, and no clinically significant abnormalities
Be able to demonstrate the ability to comply with the inhalation instructions for Test Product administration (Research ENDS S TA U001 and NICORETTE Inhalator), visually confirmed by clinic staff at Screening visit
Be able to verbalize understanding of the consent forms, provide written informed consent, and verbalize willingness to comply with the study procedure
Have 5-50 days of use of any ENDS product in their life and no use within 7 days before Screening
Have no more than 20 days of use of the NICOTROL Inhaler in their life and no use within the 7 days before Screening

For Group 2: in order to participate in the study, potential subjects must:

Be males and females between 21 and 65 years of age inclusive
Be current daily users of a commercially available ENDS product, with e-liquids of nicotine concentration 10 to 20 mg/mL
Consume at least 1 mL per day of e-liquid in their ENDS product
Not smoke more than 2 combustion (non menthol) cigarettes per day
Have carbon monoxide ≤15 ppm at Screening to confirm limited smoking status
Have blood cotinine ≥100 ng/mL at Screening to confirm nicotine dependence
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; ECG; and clinical chemistry, urine and hematological laboratory tests
Be willing to refrain from using any source of nicotine 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
Have an ECG performed that demonstrates normal sinus rhythm, normal conductivity, and no clinically significant abnormalities
Be able to demonstrate the ability to comply with the inhalation instructions for Test Product administration (Research ENDS S TA U001), visually confirmed by clinic staff at Screening visit
Be willing to use tobacco-flavored product
Be able to verbalize understanding of the consent forms, provide written informed consent, and verbalize willingness to comply with the study procedure

Exclusion Criteria:

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
Have any medical history or condition (including physical) considered by the Principal Investigator and/or admitting physician to place the subjects at increased risk or preclude safe and/or successful completion of the study
Have any history of substance abuse, including alcohol abuse within the last 3 months
Have a positive result for any drug of abuse (opiates, benzodiazepines, barbiturates or related CNS depressants, amphetamines or related stimulants, or marijuana) at screening or Day -1
Be cognitively impaired to a degree that would affect participation. An adequate level of reading and comprehension is needed in order to complete various forms (e.g., behavioural assessments) that are used as dependent variables
Have active syphilis (based on the standard confirmatory test (e.g., FTB-abs))
Be undergoing HIV treatment with antiviral and non-antiviral therapy or treatment for HIV-related opportunistic infection
Do not actively meet the inclusion criteria at the time of screening