Study to Assess PK, PD, Nicotine Extraction, Palatability, Subjective Effects of Nicotine Pouches - Daily Nicotine Users

NCT06170138 | Unknown

• 1 other identifier: AMP-01-101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an explorative, open-label, randomised, 3-way cross-over study to assess pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability, nicotine extraction, palatability and subjective effects after single use of nicotine pouches in daily nicotine users.

Conditions

Nicotine Use Disorder

Keywords

nicotine; nicotine pouch products

Outcome Measures

Primary Outcomes (7)

• AUC from timepoint 0 to infinity (AUCinf),

  Non-adjusted and baseline-adjusted PK parameters for nicotine including area under the curve (AUC) from timepoint 0 to infinity (AUCinf).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• AUC from timepoint 0 to timepoint t (AUC0-t)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including AUC from timepoint 0 to timepoint t (AUC0-t).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• AUC from timepoint 0 to 30 minutes (AUC0-30min)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including AUC from timepoint 0 to 30 minutes (AUC0-30min).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• AUC from timepoint 0 to 60 minutes (AUC0-60min)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including AUC from timepoint 0 to 60 minutes (AUC0-60min).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• Maximum plasma concentration (Cmax)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including maximum plasma concentration (Cmax).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• Time to Cmax (Tmax)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including time to Cmax (Tmax).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• Terminal elimination half-life (T1/2)

  Non-adjusted and baseline-adjusted PK parameters for nicotine including terminal elimination half-life (T1/2).

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

Secondary Outcomes (6)

• In vivo extracted amount (mg/unit) of nicotine

  Visit 2-4 (1 visit = 1 day).

• In vivo extracted fraction (%) of nicotine

  Visit 2-4 (1 visit = 1 day).

• Highest recorded increase (Emax) in pulse rate from baseline.

  Visit 2-4 (1 visit = 1 day): Pre-use and at 5, 10, 15, 20, 30, 40, 50, 60 minutes, 1 hour and 30 minutes, 2, 4, 6 and 8 hours post-IP use on visit 2, 3 and 4.

• Mean score for each palatability question 30 minutes after start of IP use.

  Visit 2-4 (1 visit = 1 day): 30 minutes post-IP use on visit 2, 3 and 4.

• Urge-to-use

  Visit 2-4 (1 visit = 1 day) : Pre-use and at 30, 60 minutes and 2 hours, post-IP use on visit 2, 3 and 4.

Study Arms (3)

Ampli-01, 3 mg, nicotine pouch

EXPERIMENTAL

Subjects will report to the study site for a screening visit followed by 3 visits with a single IP use (Visits 2 to 4) on separate days.There will be at least 1 day between Visits 2, 3 and 4, respectively, where the subjects are allowed ad libitum use of their own nicotine product of choice. Each visit will last one day.

Other: Test product 1 - Test product 2 - Comparator product

Ampli-01, 6 mg, nicotine pouch

EXPERIMENTAL

Subjects will report to the study site for a screening visit followed by 3 visits with a single IP use (Visits 2 to 4) on separate days.There will be at least 1 day between Visits 2, 3 and 4, respectively, where the subjects are allowed ad libitum use of their own nicotine product of choice. Each visit will last one day.

Other: Test product 1 - Test product 2 - Comparator product

ZYN Cool Mint Mini Dry, 6 mg nicotine /pouch

ACTIVE COMPARATOR

Subjects will report to the study site for a screening visit followed by 3 visits with a single IP use (Visits 2 to 4) on separate days.There will be at least 1 day between Visits 2, 3 and 4, respectively, where the subjects are allowed ad libitum use of their own nicotine product of choice. Each visit will last one day.

Other: Test product 1 - Test product 2 - Comparator product

Interventions

Test product 1 - Test product 2 - Comparator product OTHER

Each subject will be randomised to 1 of 6 IP use sequences The IPs will be administered as single pouches in a pre-determined randomised order. Test product 1 - Ampli-01 3 mg, nicotine pouch Test product 2 - Ampli-01 6 mg, nicotine pouch Comparator product - ZYN Cool Mint Mini Dry 6 mg nicotine /pouch Single 30-minutes IP use on 3 occasions (Visits 2 to 4).

Ampli-01, 3 mg, nicotine pouch; Ampli-01, 6 mg, nicotine pouch; ZYN Cool Mint Mini Dry, 6 mg nicotine /pouch

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Subjects who have used oral tobacco/nicotine products for ≥1 year, with a minimum daily consumption of 5 or more pouches with a pouch strength of 3-9 mg nicotine/pouch. Concomitant occasional use of other nicotine products (e.g., smoking, vaping) is allowed, as judged by the Investigator at the time of the screening visit.
• Healthy male or female subject aged 25 to 55 years, inclusive, at the time of the screening visit.
• Female subjects of childbearing potential must be willing to use a sufficient contraceptive method for the duration of the study, this includes mechanical barrier (e.g., a male condom or a female diaphragm), combined \[oestrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, transdermal\], progestogen-only hormonal anticonception associated with inhibition of ovulation \[oral, injectable, implantable\], intra uterine device (IUD) or intra uterine system (IUS). Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject.
• Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 and a minimum weight of ≥ 50 kg.
• Medically healthy subject without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator.
• Positive urine cotinine test (≥200 ng/mL) at the screening visit.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges: - Systolic blood pressure: \<90 or \>140 mmHg, or - Diastolic blood pressure \<50 or \>90 mmHg, or - Pulse \<40 or \>90 bpm
• Any surgical or medical condition, including abnormal salivation (also pharmaceutically induced), or history thereof, which, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism or excretion of the IP or may either put the subject at risk because of participation in the study, influence the results, or the subject's ability to participate in the study.
• A history of diagnosed severe allergy/hypersensitivity or ongoing manifestations of severe allergy/hypersensitivity to aroma compounds (including fragrances and/or flavourings), as judged by the Investigator.
• Any planned major surgery within the duration of the study.
• Subjects who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the study.
• Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or HIV.
• Positive screening result for drugs of abuse or alcohol at the screening visit or on admission to the study site prior to IP use at Visits 2 to 4. (Positive results that are expected given the subject's medical history and prescribed medications can be disregarded as judged by the Investigator.)
• Presence or history of drug abuse, as judged by the Investigator.
• History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
• History of, or current use of anabolic steroids, as judged by the Investigator.
• Current, ongoing use of beta-adrenergic blocking agents (beta blockers), including pro re nata (as needed) use.
• Current, ongoing use of any medication known to be able to interfere with adrenaline testing, including but not limited to central nervous system stimulants (amphetamines), also including pro re nata (as needed) use, as judged by the Investigator.
• Plasma donation within 1 month of the screening visit or blood donation (or corresponding blood loss) during the last 3 months prior to the screening visit.
• Subjects who intend to change their nicotine consumption habit, including the intention to stop using nicotine products, within the next 3 months from the screening visit, as judged by the Investigator.

Sponsors & Collaborators

• Amplicon AB: lead

Study Sites (1)

Clinical Trial Consultants AB (CTC)

Uppsala, SE-752 37, Sweden

RECRUITING

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Erik Rein-Hedin, MD

  Clinical Trial Consultants AB (CTC)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Franzén, PhD

CONTACT

+46 (0)72 890 67 77; anna.franzen@emplicure.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each subject will be randomised to 1 of 6 IP use sequences The IPs will be administered as single pouches in a pre-determined randomised order. Test product 1 - Ampli-01 3 mg, nicotine pouch Test product 2 - Ampli-01 6 mg, nicotine pouch Comparator product - ZYN Cool Mint Mini Dry 6 mg nicotine /pouch Single 30-minutes IP use on 3 occasions (Visits 2 to 4).

Study Record Dates

• First Submitted: November 23, 2023
• First Posted: December 14, 2023
• Study Start: November 24, 2023
• Primary Completion: December 14, 2023
• Study Completion: March 1, 2024
• Last Updated: December 14, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)