Clinical trial NCT05317195: Nicotine Pharmacokinetics and Subjective Effects of Nicotine Pouch 1.0 Compared to Velo® Ice Cool and Zyn® Cool Mint Mini Dry in Healthy Smokers
Official title: A Single-center, Randomized, Controlled, Open-label Study to Investigate the Nicotine Pharmacokinetic Profiles and Subjective Effects of Four Variants of Nicotine Pouch 1.0 Compared to Velo® Ice Cool and Zyn® Cool Mint Mini Dry in Healthy Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Nicotine
Keywords: Nicotine-containing products
Nicotine delivery
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 31
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a single-center, randomized, controlled, open-label, cross-over study in healthy smoking subjects to investigate the nicotine pharmacokinetic (PK) profiles of 4 variants of Nicotine pouch 1.0 compared to marketed Velo - Nicotine Pouch (NP) and Zyn-NP. In addition, pharmacodynamic (PD) effects will be evaluated to provide further insights on Nicotine pouch 1.0 product acceptance and abuse liability. The study will be conducted with 3 periods and 6 sequences in a Williams design (cross-over).

Detailed description: 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 Smokers

Who carried out the research? This research was sponsored and funded by Philip Morris Products S.A.

What public involvement there was in the study? 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 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 and Day 3.

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.

Eligibility criteria: Main Inclusion Criteria:

* Subject has smoked continuously for at least the last 3 years prior to the Screening visit.
* Subject has smoked ≥ 10 commercially available cigarettes per day for 4 weeks prior to Screening Visit and Admission. Smoking status will be verified based on a urinary cotinine test (cotinine ≥ 500 ng/mL).
* Subject does not plan to quit using tobacco and/or nicotine products within the next 3 months.
* Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period.

Main Exclusion Criteria:

* As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical.
* Subject is legally incompetent, or physically or mentally incapable of giving consent.
* Subject has a clinically relevant disease that requires medication, which as per the judgment of the Investigator would jeopardize the safety of the subject.
* Subject has donated or received whole blood or blood products within 30 days prior to Screening Visit.
* Subject has a BMI \< 18.5 kg/m2 or \> 32.0 kg/m2 (Europe) or \> 35.0 kg/m2 (USA).
* For women only: subject is pregnant (does not have negative pregnancy test at Screening Visit and at Admission) or is breastfeeding.

Primary outcomes:
measure: Background-corrected Maximum Plasma Concentration [Cmax]
timeFrame: T0 = start of product use. Blood was drawn 5 minutes prior to T0, and then 5, 10, 15, 20, 25, 30, 35, 40 minutes, 1, 3, and 6 hours after T0, on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon).
measure: Background-corrected Time to the Maximum Concentration [Tmax]
timeFrame: T0 = start of product use. Blood was drawn 5 minutes prior to T0, and then 5, 10, 15, 20, 25, 30, 35, 40 minutes, 1, 3, and 6 hours after T0, on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon).
measure: Area Under the Background-corrected Concentration-time Curve (AUC) From Start of Product Use, Extrapolated to Infinity (AUC Infinity)
timeFrame: T0 = start of product use. Blood was drawn 5 minutes prior to T0, and then 5, 10, 15, 20, 25, 30, 35, 40 minutes, 1, 3, and 6 hours after T0, on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon).
Secondary outcomes:
measure: Score of Cigarette Craving by the Visual Analog Scale (VAS)-Craving Assessment
timeFrame: Measured before, and up to 6 hours post-product use on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon)
measure: Score of "in the Moment" Product Liking by the VAS-liking Assessment
timeFrame: Measured up to 1 hour post-product use on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon)
measure: Score of Overall Product Liking by the VAS-liking Assessment
timeFrame: Measured after 30 minutes product use on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon)
measure: Score of Product Satisfaction by the VAS-satisfaction Assessment
timeFrame: Measured on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon)
measure: Score of Product Intention to Use Again by the VAS-intention to Use Again Assessment
timeFrame: Measured on day 1 (morning/afternoon), day 2 (morning/afternoon), and day 3 (morning/afternoon)
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Celerion
state: Northern Ireland
Study officials:
affiliation: Celerion
name: Rajkumar Chetty, MD
role: PRINCIPAL_INVESTIGATOR
References: