A Single-centre, Dose Titration Study in Healthy Volunteers (Smokers and Non-smokers) to Evaluate the Capacity of 2-cyanoethylmercapturic Acid (CEMA) to Detect Low Level of Cigarette Smoking Exposure
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Smoking
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- Levels of CEMA, a biomarker of exposure to acrylonitrile, in 24-hour urine of smokers smoking 2 or 4 conventional cigarettes
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
The purpose of this study is to develop a fit-for-purpose biochemical verification tool that can be used to detect concomitant use of a few (less than 5) conventional cigarettes.
Detailed Description
This study will be performed in two parts. The first part, Part A, is a dose titration study in healthy smokers with incremental cigarette consumption performed in confinement. The second part, Part B, is an observational study on healthy non-smokers in an ambulatory setting PART A (smokers only) A screening visit will be conducted within 4 weeks prior to admission to the investigational site. The 8-day confinement period consists of the admission day (Day1), 1 day ad-libitum smoking (Day0), 3 days of smoking abstinence (Day1-3), 2-day exposure period smoking 2 and 4 cigarettes (Day4-5), and the day of discharge (Day6) followed by a 7-day safety follow-up period. Urine collection will be performed for each subject from Day0 to Day5 in 4 intervals. PART B (non-smokers) Screening visit will be conducted within 4 weeks prior to the ambulatory Visit 1 (collection of 24-hour urine and spot urine) to the investigational site. The minimum interval between the screening and Visit 1 is of 7 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Common criteria to smokers and non-smokers
- •Subject is able to understand the information provided in the Subject Information sheet and Informed Consent Form (ICF)
- •Subject has signed the ICF
- •Subject of Caucasian origin
- •Aged from 23 to 55 years
- •Having acceptable health conditions as judged by the Investigator at the screening visit based on clinical laboratory parameters (clinical biochemistry, urine analysis and standard haematology), spirometry, serology, urine drug screen, vital signs, physical examination, ECG, and medical history
- •Specific to smokers
- •Current smoker based on self-reporting who smoke 5 to 15 commercially available non-mentholated conventional cigarettes (no brand restrictions) with a maximum tar yield of 10 mg (ISO method, as labelled on the cigarette package) smoking at least for the last 3 consecutive years. The smoking status will be verified at screening based on a urinary cotinine test (cotinine ≥200ng/ml)
- •Subject is willing to smoke according to the smoking regimen of the study
- •Specific to non-smokers
Exclusion Criteria
- •Common criteria to smokers and non-smokers
- •As per judgement of the Investigator, any subject who cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason)
- •Any clinically relevant gastrointestinal, renal, hepatic, neurological, haematological, endocrine, oncological, urological, immunological and cardiovascular diseases or any other condition including clinically significant abnormal laboratory parameters that, in the opinion of the Investigator, could jeopardise the safety of the subject or impact the validity of the study results
- •Lung cancer, upper respiratory tract cancers, chronic respiratory diseases or any other clinically significant pulmonary diseases according to the judgement of the Investigator
- •Any medical conditions requiring smoking cessation (e.g., recent acute cardiovascular event, diabetes mellitus, Chronic Obstructive Pulmonary disease)
- •Subject with body mass index \< 18.5 or ≥ 30 kg/m2
- •As per judgement of the Investigator, medical conditions which require or will require in the course of the study a medical intervention (e.g., start of treatment, surgery, hospitalisation) which may interfere with the study participation and/or study results
- •Donation or receipt of whole blood or blood products within 3 months prior to the screening visit
- •Participation in any clinical studies within 3 months before the screening visit
- •Current or former employee of the tobacco industry, or of their first-degree relatives (parent, sibling, child)
Outcomes
Primary Outcomes
Levels of CEMA, a biomarker of exposure to acrylonitrile, in 24-hour urine of smokers smoking 2 or 4 conventional cigarettes
Time Frame: After smoking 2 or 4 conventional cigarettes, within 24 hours
To demonstrate that CEMA, used as a urinary biomarker, can identify subjects who have smoked 4 or less conventional cigarettes
Secondary Outcomes
- Levels of CEMA in 24-hour urine, carboxyhaemoglobin (COHb) in blood and carbon monoxide in exhaled breath of smokers smoking 2 or 4 conventional cigarettes(After smoking 2 or 4 conventional cigarettes, within 24 hours)
- Levels of CEMA, a biomarker of exposure to acrylonitrile, in 24-hour and spot urine of non-smokers(24 hours)