Clinical trial NCT03294356: CSD170304: Study to Assess Nicotine Uptake in Smokers From Electronic and Combustible Cigarettes
Official title: CSD170304: An Unblinded, Parallel, Randomized Study to Assess Nicotine Uptake in Smokers From Electronic and Combustible Cigarettes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Lead sponsor: RAI Services Company
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2017-09-27
Enrollment: 210
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: To determine the rate and amount of nicotine uptake with 10-minute ad libitum use of five different marketed electronic cigarettes, or one combustible cigarette (CC). Furthermore, to measure overall product liking by subjects to assess potential willingness to seek out the Electronic Cigarette (EC) again in the future.

Detailed description: This will be a single-center, randomized, open-label, parallel study during which up to 210 healthy adult subjects, consisting of 35 subjects per product group, will be enrolled. Subjects will be evaluated for plasma nicotine uptake, as well as overall product liking. The study will involve the use of five different marketed ECs or one CC in tobacco consumers who are exclusive smokers (i.e., naïve EC users) or dual users of cigarettes and ECs (i.e., intermittent EC users).

Eligibility criteria: Inclusion Criteria:

1. Able to read, understand, and willing to sign an Informed Consent Form (ICF) and complete questionnaires written in English.
2. Generally healthy males and females, 21 to 60 years of age, inclusive, at Screening Visit.
3. Subjects must meet one (a or b) of the following tobacco use conditions:

   1. Exclusive cigarette smoker who self-reports smoking ≥ 10 cigarettes per day for at least 6 months prior to Screening Visit. Brief periods of abstinence more than 30 days prior to Screening due to illness, quit attempt, or clinical study participation will be allowed at the discretion of the Principal Investigator (PI).
   2. Dual user of CCs and ECs who self-reports:

   i. Smoking ≥ 10 cigarettes per day for at least 6 months prior to Screening Visit. Brief periods of abstinence more than 30 days prior to Screening due to illness, quit attempt, or clinical study participation will be allowed at the discretion of the PI; and ii. Using a nicotine-containing "cig-a-like" EC or a tank system EC either daily or at least weekly for at least 3 months prior to Screening Visit.
4. Willing to be confined overnight and abstain from tobacco- and nicotine-containing product use (with the exception of study IP use) for 12 hours prior to IP use through Study Discharge.
5. Willing to use assigned IP during the study according to protocol.
6. Expired breath carbon monoxide (ECO) level is ≥ 10 parts per million (ppm) at the Screening Visit and Study Day 1.
7. Positive urine cotinine test at the Screening Visit and Study Day 1.
8. No intent to quit smoking or vaping from Screening to Study Day 2.
9. Females of childbearing age must be willing to use a form of contraception acceptable to the PI from the time of signing informed consent until Study Discharge, or be surgically sterile for at least 90 days prior to the Screening Visit.

Exclusion Criteria:

1. Presence of clinically significant or unstable/uncontrolled acute or chronic medical condition at the Screening Visit, as determined by the PI, that would preclude a subject from participating safely in the study (e.g.,, uncontrolled hypertension, chronic lung disease, cardiac disease, neurological disease, or psychiatric disorders) based on safety assessments such as clinical laboratory tests, pregnancy tests, medical history, and physical/oral examinations.
2. At risk for heart disease, as determined by the PI.
3. Systolic blood pressure of \> 160 mmHg or a diastolic blood pressure of \> 95 mmHg, measured after being seated for 5 minutes.
4. Weight of ≤ 110 pounds.
5. Poor peripheral venous access.
6. Use of medicine for treatment of depression, unless on a stable dose for the past 6 months prior to screening and deemed clinically stable by the PI.
7. Current on scheduled treatment(s) for asthma within the past consecutive 12 months prior to screening. If potential subject is on an as-needed treatment, such as rescue inhalers, subject may be included at the PI's discretion pending approval from the Medical Monitor.
8. Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically or cryogenically removed.
9. Use of any medication or substance that aids in smoking cessation, including but not limited to any nicotine replacement therapy (NRT) (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), or lobelia extract, within 30 days prior to the Screening Visit.
10. History or presence of hemophilia or other bleeding disorders.
11. History or presence of clotting disorders with concomitant use of anticoagulants (e.g., clopidogrel \[Plavix®\], warfarin \[Coumadin®, Jantoven®\], aspirin \[\> 325 mg/day\]).
12. Participation in another clinical trial within 30 days prior to the time of consent. The 30-day window for each subject will be derived from the date of the last study event in the previous study to the time of consent of the current study.
13. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV).
14. Females who have a positive pregnancy test or who are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
15. Females ≥ 35 years of age currently using systemic, estrogen-containing contraception or hormone replacement therapy.
16. A positive urine drug screen without disclosure of prescribed corresponding concomitant medication(s) at the Screening Visit or on Study Day 1.
17. A positive alcohol breathalyzer result at the Screening Visit or on Study Day 1.
18. Employed by a tobacco or nicotine-manufacturing company, the study site, or handles tobacco or nicotine-containing products as part of their job.
19. Determined by the PI to be inappropriate for the study, including a subject who is unable to communicate or unwilling to cooperate with the clinical staff.

Primary outcomes:
measure: Cmax (Maximum baseline-adjusted nicotine plasma concentration)
timeFrame: -5, -0.5, 3, 5, 8, 10, 11, 12, 15, 20, 30, 60 Minutes
measure: AUCnic0-60
timeFrame: -5, -0.5, 3, 5, 8, 10, 11, 12, 15, 20, 30, 60 Minutes
Secondary outcomes:
measure: Tmax
timeFrame: -5, -0.5, 3, 5, 8, 10, 12, 15 Minutes
measure: AUCnic0-15
timeFrame: -5, -0.5, 3, 5, 8, 10, 12, 15 Minutes
measure: PLoverall
timeFrame: 13 Minutes
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Clinical Research Consortium (CRC)
state: Arizona
city: Lexington
country: United States
facility: Central Kentucky Research Associates (CKRA)
state: Kentucky
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials (SLCT)
state: Missouri
city: Dayton
country: United States
facility: Midwest Clinical Research (MCRC)
state: Ohio
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research (NOCCR)
state: Tennessee
Study officials:
affiliation: Clinical Research Consortium (CRC)
name: Corey Anderson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Kentucky Research Associates (CKRA)
name: Mark Adams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Louis Clinical Trials (SLCT)
name: Daniel Gruener, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Clinical Research (MCRC)
name: Otto Dueno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New Orleans Center for Clinical Research (NOCCR)
name: William Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: