Condition category
Respiratory
Date applied
22/09/2015
Date assigned
06/10/2015
Last edited
02/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Cigarette smoking is one of the biggest causes of illness and death in the UK. Nicotine is a chemical which is found in all tobacco products. Nicotine is extremely addictive, as it works quickly on the brain to activate neural pathways (connections in the brain) causing feelings of pleasure. Research highlighting the risks of smoking has already helped many people to quit, and there are many products on the market designed to help. Most of these products are designed to provide nicotine, without the other harmful substances contained in standard cigarettes (nicotine delivery system). A recently developed product is the “heat-not-burn” (HNB) cigarette. These HNB products heat tobacco to produce a vapor containing nicotine which is then inhaled. As tobacco is not actually lit on fire, smoke produced has a significantly reduced level of harmful toxins as compared to a conventional cigarette. The aim of this study is to find out whether a HNB 1.2 product (a HNB cigarette containing approximately 1.2 mg of nicotine) is an effective nicotine delivery system.

Who can participate?
Adults aged between 21 and 50 years in good general health, who have smoked at least 10 cigarettes a day for at least one year.

What does the study involve?
All participants “check-in” to the study centre for a total period of four days. On the first day, they are allowed to continue their usual smoking habits until 11pm. They are then asked not to smoke so that all of the nicotine leaves their system for the second day. On the third and fourth days, participants are given a HNB 1.2 product and a normal cigarette to smoke in a random order. Before and after the participants have used each product, a number of blood samples are taken so that the amount of nicotine in their body can be measured. The amount of each product that they have smoked is then recorded.

What are the possible benefits and risks of participating?
A potential benefit of participating is that participants may find a potential alternative to conventional cigarettes and be able to cut down the amount they smoke. There are not expected to be any major risks of participating, however health risks of the HNB device are expected to be similar to those of other tobacco products.

Where is the study run from?
Celerion (UK)

When is the study starting and how long is it expected to run for?
January 2015 to October 2015

Who is funding the study?
Japan Tobacco International (Geneva)

Who is the main contact?
Mrs Kirsten Gill

Trial website

Contact information

Type

Public

Primary contact

Mrs Kirsten Gill

ORCID ID

Contact details

Celerion
22-24 Lisburn Road
Belfast
BT9 6AD
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

JTGP-001

Study information

Scientific title

An assessment of the biological uptake of nicotine among healthy adult smokers following a single controlled use of "Heat Not Burn" (HNB) 1.2 and a combustible cigarette

Acronym

Study hypothesis

To characterise the nicotine uptake profiles (Cmax, tmax and AUClast) of the HNB 1.2 product and a conventional tobacco cigarette in healthy volunteers who smoke.

Ethics approval

South East Scotland REC 02, 24/8/2015, ref: 15/SS/00133

Study design

Single-centre randomised open label two period crossover study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Other

Trial type

Other

Patient information sheet

Condition

Nicotine uptake

Intervention

Potential subjects will undergo screening procedures to ensure they satisfy the inclusion and exclusion criteria of the study. During Screening, potential subjects will practice with the HNB 1.2 product under the supervision of the clinic staff to ensure that they would be willing and able to use it as required during study conduct.
Subjects will check-in to the clinic and will be allowed to smoke their usual brand cigarette products ad libitum until 23:00. Following check-in procedures, a sample will be collected for trans-3’-hydroxycotinine cotinine ratio determination. Participants will then abstain from nicotine and tobacco product use for 24 hours (wash-out period). Days 1 and 2 will be product administration days.

Each product administration day will include a controlled administration of either the HNB 1.2 product or the reference cigarette according to the randomisation schedule. The administration of the HNB 1.2 product will consist of 10 puffs for 3 minutes, at approximately 20-second intervals, or smoking one reference cigarette, 10 puffs for 3 minutes, at approximately 20-second intervals. The number of puffs from the HNB 1.2 and the reference cigarette will be documented by the clinical staff. The MLE from the HNB 1.2 will be assessed from the change in product weight from before to after use. Used cigarette butts will be collected and saved to assess MLE nicotine from the filter tips.

Subject health status will be evaluated on Day 2 prior to discharge. Serial blood samples will be collected at approximately 10 minutes prior to and at 2, 3, 4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60, 90, and 120 minutes following the start of the controlled product administration to determine plasma nicotine concentrations. Nicotine PK parameters will be determined using a non-compartmental approach. Parameters will include Cmax, tmax, AUClast, AUC0-∞, t1/2, F(AUC0 ∞), tlast, Clast, λz, number of points, λz_lower, λz_upper, R2adj, and AUCext%. Baseline adjustments may be performed to correct for pre-administration nicotine concentration if deemed appropriate. Nicotine concentrations and PK parameters will be listed by subject and summarized by study product using descriptive statistics.

Intervention type

Device

Phase

Drug names

Primary outcome measures

Uptake of nicotine from the HNB 2.1 product as measured using plasma nicotine concentrations obtained from blood samples taken at 2, 3 ,4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60 and 90 minutes following use of the HNB 1.2 product.

Secondary outcome measures

1. Nicotine pharmacokinetic parameters (e.g. maximum nicotine concentration (Cmax) and time to Cmax (tmax)) measured using plasma nicotine concentrations obtained from blood samples taken at 2, 3 ,4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60 and 90 minutes following use of the HNB 1.2 product
2. Volunteer mouth level exposure (MLE) to nicotine during use of the HNB 2.1 product, as measured by the difference in weight of HNB 2.1 product + its associated pod insert before and after product use
3. Volunteer mouth level exposure (MLE) to nicotine during use of the CC1 product, as measured by assessing the amount of nicotine present in the product filter after product use
4. Volunteer inhalation to non-inhalation ratios during use of the HNB 2.1 product as measured by vidual analogue scare (VAS) questionnaire following use of the HNB 1.2 product

Overall trial start date

06/01/2015

Overall trial end date

10/10/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 21 to 50 years of age
2. Good general health
3. Smoker for at least 12 months prior to check-in and currently smokes an average of 10 or more manufactured cigarettes per day (no restriction on brand-style, king size [~83 – 85 mm] and 100s [~98 – 100 mm] only)
4. Positive urine cotinine at screening (> 200 ng/mL) at screening
5. Female subjects must be non-pregnant and non-lactating
5. Pre-menopausal female subjects must be surgically sterile, use an investigator-approved method of birth control, or agree to be sexually abstinent from 14 days prior to check-in through the end of the study

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

Up to 24 participants

Participant exclusion criteria

1. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary (especially bronchospastic diseases), immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results
2. Clinically significant abnormal findings on the physical examination, medical history, ECG, or clinical laboratory results at Screening or Check-in, in the opinion of the Investigator
3. Positive test for HIV, HBsAg, or HCV
4. An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment within 2 weeks prior to Check-in
5. Fever (>38C) at Screening or at Check-in
6. Systolic blood pressure <90 mmHg or >150 mmHg, diastolic blood pressure <40 mmHg or >95 mmHg, or pulse rate <40 bpm or >99 bpm at screening
7. BMI <18 kg/m2 or >35 kg/m2 at screening
8. Use of prescription anti-diabetic medication and/or insulin therapy within 12 months of day 1 product administration.
9. Use of medications known to interact with CYP2A6 (including, but not limited to, amiodarone, desipramine, isoniazid, ketoconazole, miconazole, phenobarbital, rifampin, tranylcypromine, methoxsalen) within 3 months prior to day 1 product administration
10. Use of inhalers to treat any medical condition within 3 months prior to day 1 product administration and throughout the study
11. Positive urine screen for alcohol or drugs of abuse at screening or at check-in
12. History or presence of alcoholism or drug abuse within the past 2 years prior to screening
13. Drink alcohol in excess of 21 glasses/units per week for males or 14 glasses/units per week for females, with one unit = 150 ml of wine or 360 mL of beer or 45 mL of 45% alcohol
14. Males who have donated blood within 12 weeks or females who have donated blood within 16 weeks prior to day 1 product administration.
15. Donation of bone marrow within the last 6 months prior to day 1 product administration
16. Participation in a previous clinical study for an investigational drug, biologic, medical device, or tobacco product within 90 days prior to day 1 product administration
17. Planning to quit smoking during the study period or postponing a quit attempt in order to participate in the study
18. Use of any prescription smoking cessation treatments, including, but not limited to, varenicline (Champix®) or buproprion (Zyban®) within 3 months prior to day 1 product administration and throughout the study
19. Known hypersensitivity to glycerol or propylene glycol
20. Subject or a first-degree relative is a current or former employee of the tobacco industry or a named party or class representative in litigation with the tobacco industry

Recruitment start date

01/09/2015

Recruitment end date

03/10/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Celerion
22-24 Lisburn Road
Belfast
BT9 6AD
United Kingdom

Sponsor information

Organisation

Japan Tobacco International

Sponsor details

JT International S.A.
1 Rue de la Gabelle
Geneva
1211 Geneva 26
Switzerland

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Japan Tobacco International

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Publication in a peer reviewed journal on completion of the study. Additionally study results will be dissemmination at tobacco related conferences and workshops such as CORESTA (Cooperation Centre for Scientific Research Relative to Tobacco) and TSRC (Tobacco Science Research Conference).

Intention to publish date

01/11/2016

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

02/03/2016: Internal review.