Uptake of nicotine following a single use of "Heat Not Burn" (HNB) 1.2 and a cigarette
| ISRCTN | ISRCTN88682435 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN88682435 |
| Secondary identifying numbers | JTGP-001 |
- Submission date
- 22/09/2015
- Registration date
- 06/10/2015
- Last edited
- 30/04/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
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
Contact information
Public
Celerion
22-24 Lisburn Road
Belfast
BT9 6AD
United Kingdom
Study information
| Study design | Single-centre randomised open label two period crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| 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 |
| 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(s) | South East Scotland REC 02, 24/8/2015, ref: 15/SS/00133 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | 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 study start date | 06/01/2015 |
| Overall study end date | 10/10/2015 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Up to 24 participants |
| 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 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 (>38C) 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
- Northern Ireland
- United Kingdom
Study participating centre
Belfast
BT9 6AD
United Kingdom
Sponsor information
Industry
JT International S.A.
1 Rue de la Gabelle
Geneva
1211 Geneva 26
Switzerland
"ROR" |
https://ror.org/04f5ks076 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/11/2016 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| 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). 30/04/2018: Results presented at CORESTA 2016 (abstract: https://www.coresta.org/abstracts/pharmacokinetics-nicotine-following-single-controlled-use-new-type-tobacco-heated-tobacco , slides: https://www.jt-science.com/sites/default/files/2017-08/2016-O2.pdf ) |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
30/04/2018: Conference proceedings and slides added to publication and dissemination plan.
27/04/2018: No publications found, verifying study status with principal investigator
02/03/2016: Internal review.
