The effects of reduced toxicant prototype (RTP) cigarettes on biomarkers of exposure and of biological effect versus commercial cigarettes when smoked by healthy adult smokers.

Not Applicable

Completed

• Conditions: Smoking; Signs and Symptoms

• Registration Number: ISRCTN81286286
• Lead Sponsor: British American Tobacco (Investments) Ltd (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-19
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

Universal Inclusion Criteria
1. Participants may be of either sex and of any ethnic origin
2. Male and female participants must weigh at least 52 kg and 45 kg, respectively, and fall within the normal range according to accepted normal values of Body Mass Index (BMI) 18.5-30.0 kg/m2 (inclusive)
3. Participants must have no clinically significant abnormal findings, as judged by the project investigator (PI) or his appropriately qualified designee, on the physical examination, ECG, clinical laboratory test results, lung function tests or medical history during screening.
4. Participants must give voluntary written informed consent to participate in this study
5. Participants must be willing to refrain from consuming alcohol within 72 hours prior to the first day of each in-clinic evaluation visit
6. Participants must be willing to refrain from consuming grilled, fried or barbequed food and avoid being in the presence of the cooking of grilled, fried or barbequed food for 48 hours prior to the first day of each in-clinic evaluation visit
7. Female participants must not be pregnant or breastfeeding at screening and at check-in of each in-clinic evaluation period and be using a reliable method of contraception as per definition of Note 3 of ICH M3 Guideline

Inclusion Criteria for Smoking Groups:
1. Participants must be aged 23 to 55 years of age (inclusive)
2. Participants must be regular smokers whose chosen brand is both within one of the required ISO tar bands and has blend style/mechanics similar to those found in brands sold in Germany
3. Participants must have smoked their chosen brand for a minimum of 6 months and have smoked for at least 5 years prior to screening
4. Participants must typically smoke between 10 and 30 cigarettes per day (CPD)
5. Participants must be willing to switch to an RTP cigarette and smoke only the products provided to them during the study
6. Have a urinary cotinine level of >100 ng/mL

Inclusion Criteria for Ex-Smoking Group:
1. Participants must be aged 28 to 55 years of age (inclusive)
2. Participants must not have smoked for at least five years but must have been regular cigarette smokers, smoking 10 to 30 CPD, for at least five years prior to quitting
3. Participants must have a urinary cotinine level of <10 ng/mL

Inclusion Criteria for Never-Smoking Group:
1. Participants must be aged 28 to 55 years of age (inclusive)
2. Participants must not have smoked > 100 cigarettes in their lifetime, and none during the previous 5 years
3. Participants must have a urinary cotinine level of <10 ng/mL

Documented exceptions to the inclusion criteria may be permitted at the discretion of the PI or sub investigator in agreement with the Sponsor providing there would be no additional risk involved for the participant and there would be no impact on the realisation of the scientific objectives of the study.

Exclusion Criteria

Universal Exclusion Criteria
1. Participants may be excluded from the study if there is evidence of any of the following criteria at Screening, or at any time during the study as appropriate
2. Participants who have clinically relevant gastrointestinal, renal, hepatic, neurologic, haematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition that, in the opinion of the PI or his appropriately qualified designee, would jeopardize the safety of the participant or impact the validity of the study results.
3. Participants who have clinically relevant abnormal findings on the physical examination, medical history, or clinical laboratory results unless deemed not clinically significant by the PI or his appropriately qualified designee
4. Participants who have participated in a previous clinical trial within 30 days prior to Day 1
5. Participants who have donated or lost 400 mL of blood or more within 90 days prior to Day 1
6. Participants who have donated plasma within 7 days prior to Day 1
7. Participants who have an acute illness (e.g. upper respiratory tract infection, viral infection, etc.) requiring treatment within 4 weeks prior to Day 1
8. Participants who regularly use any nicotine or tobacco products other than commercially manufactured filter cigarettes
9. Participants who are self-reported non-inhalers (smokers who draw smoke from the cigarette into the mouth and throat but do not inhale). Participants who are observed as non-inhalers on Day 12 by the clinic staff will be excluded
10. Participants who have a history of drug or alcohol abuse within 24 months prior to screening
11. Participants who have a positive alcohol breath test and urine screen for drugs of abuse at Screening or Day 1
12. Participants who have a positive HIV or hepatitis screen at Screening
13. Participants who have used prescription or over the counter (OTC) bronchodilator medication (e.g. inhaled or oral â-agonists) to treat a chronic condition within the 12 months prior to Day 1
14. Participants who have used any medication which interferes with the cyclo-oxygenase pathway (anti-inflammatory drugs such as aspirin or ibuprofen) within 14 days of Day 1
15. Participants who have used any prescribed systemic medication within 14 days of Day 1 (except for hormonal contraceptive and hormone replacement therapy)
16. Participants who have used any drugs or substances (except tobacco) known to be strong inducers or inhibitors of CYP enzymes (formerly known as cytochrome P450 enzymes) within 28 days prior to Day 1
17. Participants who performed strenuous physical activity (exceeding the participant?s normal activity levels) within 7 days prior to screening or prior to each in-clinic evaluation visit throughout the study
18. Any female participant who becomes pregnant during the course of the study will be withdrawn
19. Employees and immediate relatives of the tobacco industry, journalism, TV and radio reporting, public relations, market research, advertising and the clinic

Exclusion Criteria for Smoking Groups:
Smoking participants who, prior to enrolment, are planning to quit smoking in the next 12 months. However, participants will be informed that they are free to quit smoking and withdraw from the study at any time.

Exclusion Criteria for Non Smoking Groups:
1. Participants who smoke at any time during the study
2. Participants who are regularly exposed to second-hand smoke, such as those who

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To descriptively assess within-participant and between-group changes in the identified primary endpoints [BoE and BoBE] following a forced switch from a commercial control cigarette to a combustible RTP cigarette of equivalent ISO tar yield.

Secondary Outcome Measures

Name	Time	Method
1. To descriptively assess within-participant and between-group changes in the secondary endpoints [BoE and BoBE, QoL, smoking behaviours, physiological measures, MLE and sensory perception] following a forced switch from a commercial control cigarette to a combustible RTP cigarette of equivalent ISO tar yield.<br>2. To descriptively assess changes in the primary and secondary endpoints following a forced switch from a commercial control cigarette to a combustible RTP cigarette of equivalent ISO tar yield in comparison to the ex-smokers and never-smokers.