Nicotine PK of NP1.0, Velo-NP and Zyn-NP in healthy smokers
Research type
Research Study
Full title
A single-centre, randomized, controlled, open-label study to investigate the nicotine pharmacokinetic profiles and subjective effects of 4 variants of Nicotine pouch 1.0 compared to Velo ice cool and Lyft cool Mint mini dry in healthy smokers
IRAS ID
311926
Contact name
Rajkumar Chetty
Contact email
Sponsor organisation
Philip Morris Products S.A.
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 1 months, 5 days
Research summary
Research Summary
The sponsor is evaluating the tobacco-free Nicotine pouches as an alternative to tobacco-containing smoking products currently available in the market. The sponsor would like to compare their own products with the other similar Nicotine pouches already on the market to assess the Nicotine absorption and subjective effects.
Summary of Results
Study Title:
Nicotine Pharmacokinetics and Subjective Effects of Nicotine Pouch 1.0 Compared to Velo® Ice Cool and Zyn® Cool Mint Mini Dry in Healthy SmokersWho carried out the research? (including details of sponsor, funding and any competing interests) This research was sponsored and funded by Philip Morris Products S.A.
What public involvement there was in the study (how many people, what their relevant lived experience was, and what they did) The study recruited 31 healthy adults who were currently smoking.
Where and when the study took place?
The study was conducted at a clinical trial facility managed by a contract research organization in Belfast, Northern Ireland, from March 15th to August 18th 2022.Why was the research needed?
The research was needed to understand the pharmacokinetic profiles of four variants of a nicotine pouch.What were the main questions studied?
The study measured the nicotine absorption of the four variants of nicotine pouch (NP-1; NP-2; NP-3; NP-4) together with two nicotine pouches marketed by other companies (Zyn-NP and Velo-NP). Participants were also asked to evaluate their experience of using the nicotine pouches.Who participated in the study?
The study recruited 31 healthy, male or female, adults aged between 21 and 65 years who were currently smoking. The subjects did not plan to quit using tobacco and/or nicotine products within the next 3 months and had smoked continuously for at least the last 3 years prior to joining the study.Each subject was given full and adequate oral and written information about the nature, purpose, possible risks and benefits of the study. Once each subject had received all the necessary information, and if he/she agreed to participate, this was documented in an Informed Consent Form with the date, time and signature of both the subject and the Investigator.
Subjects were informed that they were free to withdraw from the study at any time.
What treatments or interventions did the participants take/receive?
The participants were requested to use a tobacco-free nicotine pouch for a period of 30 minutes. Blood samples were taken before, during, and after the product use period.Participants were also asked to evaluate their experience of using the nicotine pouches, using the Product Evaluation Scale (PES).
The PES is composed of seven items which address the degree to which subjects experience seven different effects (Product Satisfaction, Psychological Rewards, Aversion, Craving Relief, Easy to Use, Comfortable Using, Concerned about Dependence) as a result of using the investigational products, rated on a 7 point scale from 1 = "not at all" to 7 = "extremely."
What medical problems (adverse reactions) did the participants have?
Overall, during the product use, seven adverse reactions occurred in two of 31 subjects, all of them being mild in severity. Six of the reported adverse reactions occurred in one subject, which were eructation (two adverse reactions), hiccups (two adverse reactions), and nausea (two adverse reactions) that were considered related to the investigational products.One subject had one adverse reaction (syncope), which was assessed to be related to study procedures.
There were no clinically significant findings in the physical examination, clinical laboratory, vital signs, or ECG assessments in this study.
What happened during the study?
The study was conducted with six periods and six sequences in a cross-over design. On Day -1, subjects were randomized to one of the six study sequences.After enrollment, subjects performed a product test with Nicotine Pouch 1.0 (NP-1) for 30 minutes (± 1 minute). One NP-1 nicotine pouch was placed between the upper lip and the gum for 30 minutes and subjects were instructed not to manipulate the pouch with the tongue or lips.
After the product test, subjects were required to abstain from any nicotine/tobacco-containing product use until the first product use on Day 1.
On Day 1 to Day 3, after at least 8 hours of abstinence from any nicotine/tobacco-containing products (nicotine wash-out), subjects used one variant of NP 1.0, Velo-NP, or Zyn-NP according to the randomized product use sequence for 30 minutes (± 1 minute). The used NP were collected for long-term storage to determine the residual nicotine after product use to estimate the amount of nicotine delivered during the 30-minute use period.
Subjects completed questionnaires about product evaluation, craving, and liking assessments.
In the morning on Day 1, 12 blood samples were collected for determination of nicotine concentration. Additional blood samples were taken for determination of the nicotine concentration on Day 2.
After Discharge at Day 3, the subjects entered a 3-day Safety Follow-Up period during which adverse reactions associated with product use reported by the subjects were collected and the follow-up of any ongoing adverse reactions was conducted by the study investigational site.
What were the results of the study?
This was an exploratory study. Differences in nicotine absorption between the study products were observed during and following a 30-minute product use period.The plasma nicotine concentration-time profiles of the four NP 1.0 variants, Velo-NP, and Zyn-NP show an increase in plasma nicotine concentrations with maximum concentrations reported around the end of the 30-minute product use period.
Across the different nicotine pouch formulations including the comparator products, there was no apparent association between nicotine content per pouch and nicotine absorption.
The time to maximum background-corrected plasma nicotine concentrations (Tmax) following the start of product use was approximately 35 minutes for all products, closely following the end of the 30-minute product use period.
Regarding the subjective effects of product use, Zyn-NP consistently scored the highest.
After abstinence from any nicotine/tobacco-containing products for at least 8 hours prior to start of product use, Craving scores were similar across all products, with mean values ranging from 61.0 (NP-1) to 68.9 (Zyn-NP).
Overall, test products seem to have similar reinforcing effects than the two competitor products, indicative of a similar abuse liability potential.
How has this study helped patients and researchers?
The participants in this study were healthy, current cigarette smokers. All participants were informed about health risks associated with smoking and were given smoking cessation advice. Participants this clinical study you will benefited from repeated and detailed general health check-ups.This clinical study may help doctors and scientists learn about nicotine pouches.
Details of any further research planned:
There is currently no further research planned with NP 1.0.Where can I learn more about this study?
More details about this study, including the study results and a copy of the study protocol, can be found on the clinicaltrials.gov website at this address: https://clinicaltrials.gov/ct2/show/NCT05317195REC name
HSC REC A
REC reference
22/NI/0032
Date of REC Opinion
11 Mar 2022
REC opinion
Further Information Favourable Opinion