Study to Evaluate Changes in Smokers Using on!® Nicotine Pouches

A Randomized, Controlled, Open-label Short-term Study to Evaluate Changes in Exposure to Harmful and Potentially Harmful Constituents in Adult Smokers Who Completely Switch to on!® Nicotine Pouches in a Clinical Setting

The purpose of this study is to generate evidence regarding the extent of reduction in exposure to selected HPHCs in adult smokers switching to on!® NPs. The study intends to determine changes in exposure to selected HPHCs by measuring biomarkers in adult smokers who completely switch from smoking to use of on!® NP compared to those who continue smoking cigarettes or stop using all tobacco products.

Study Overview

• Status: Completed
• Conditions: Tobacco Use
• Intervention / Treatment: Other: OTDN Product 1; Other: OTDN Product 2; Other: OTDN Product 3; Other: No Tobacco

Detailed Description

This is an open-label, randomized, 5 parallel-group clinical study evaluating changes in exposure to selected harmful and potentially harmful constituents (HPHCs) and product use behavior in adult smokers who are randomly assigned to 1 of the 5 groups; continue smoking, partially or completely switch to oral tobacco-derived nicotine products, or stop using any tobacco products for 7 days.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • CKRA
  • Missouri
    • Springfield, Missouri, United States, 65802
      • QPS
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • NOCCR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntary consent to participate in this study documented on the signed ICF
2. Smoking history (self-reported at screening) of an average of at least 10 but no more than 30 factory-manufactured combustible cigarettes (either menthol or non-menthol) daily for at least 12 months prior to screening. Brief periods (ie, up to 7 consecutive days) of non-smoking during the 3 months prior to screening (eg, due to illness or participation in a study where smoking was prohibited) will be permitted
3. Positive urine cotinine (≥ 500 ng/mL) at screening

4. Female subjects who are heterosexually active and of childbearing potential (eg, neither surgically sterile at least 6 months prior to check-in nor postmenopausal with amenorrhea for at least 12 months prior to check-in with follicle-stimulating hormone [FSH] levels consistent with postmenopausal status) must have been using one of the following forms of contraception for the time period indicated and agree to continue using it through completion of the study:

   • Hormonal (eg, oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to check-in, double barrier (ie, condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to check-in, an intrauterine device for at least 4 months prior to check-in
   • Exclusive partner who has been vasectomized for at least 6 months (inclusive) prior to check-in

   Female subjects of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.

5. Female subjects who are of nonchildbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to check-in:

   Hysteroscopic sterilization (including Essure® or similar nonsurgical sterilization procedures); bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy

   Or be postmenopausal with amenorrhea for at least 12 months prior to check-in and have FSH levels consistent with postmenopausal status

6. Willing to comply with the requirements of the study
7. Willing to use all 3 on!® NP after the Product Trial at check-in
8. Willing and able to abstain from cigarettes from Day 1 through the end of the study (EOS)
9. Healthy adult males and females, 21 to 65 years of age, inclusive at screening, with subjects aged 46 to 65 years being fully vaccinated for COVID-19 (SARS-CoV-2) at least 14 days before the screening visit.

Exclusion Criteria:

1. Use of any type of tobacco- or nicotine-containing products other than manufactured cigarettes (eg, e-vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to check-in
2. Self-reported puffers (ie, adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale)
3. Planning to quit smoking in the next 30 days (from screening visit)
4. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, 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
5. Clinically significant abnormal findings on the vital signs, physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results, in the opinion of the investigator
6. Positive test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at screening
7. History or presence of any type of malignant tumors
8. Current evidence or any history of congestive heart failure
9. Diabetes mellitus (fasting glucose ≥126 mg/L [7 mmol/L]) that is not controlled by diet/exercise alone, in the opinion of the investigator
10. An acute illness (eg, upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to check-in
11. Dentition that prevents subjects from using on!® NP products
12. Allergic to or cannot tolerate mint flavoring agents or phenylalanine
13. Any planned surgery from the time of screening through EOS
14. History of drug or alcohol abuse within 24 months prior to check-in
15. Fever (ie, body temperature >100.5°F) at screening or check-in. One recheck may be performed at the investigator's discretion
16. Body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at screening
17. Systolic blood pressure >150 mmHg and/or diastolic blood pressure > 90 mmHg at screening or check-in, measured after being seated for at least 5 minutes. One recheck may be performed at the investigator's discretion
18. Estimated creatinine clearance (by Cockcroft-Gault equation) < 80 mL/minute at screening
19. Serum alanine aminotransferase ≥1.5 times the upper limit of normal and/or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening
20. Positive screen for alcohol (breath) or any of the following drugs of abuse (urine), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or check-in
21. Female subjects who are pregnant (positive serum pregnancy test at screening or urine pregnancy test at check-in), lactating, or intend to become pregnant from screening through EOS
22. Use of prescription or over-the-counter bronchodilator medication (eg, inhaled or oral ß-agonists) within 12 months prior to check-in
23. Use of medications or foods known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, grapefruit, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to check-in or during the study
24. Use of antibiotic treatment within 2 weeks prior to check-in
25. Plasma donation within 7 days prior to check-in
26. Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to check-in
27. Participation in a previous clinical study for an investigational drug, device, biologic, or a tobacco product within 30 days prior to check-in
28. Participation in 2 or more Altria Client Services (ALCS) studies within the past 12-month period prior to check-in
29. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company
30. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current employee of the study site
31. Positive result for coronavirus disease (COVID)-19 (SARS-CoV-2) test at screening or check-in
32. One or more "yes" answers to any of the questions on the COVID-19 (SARS-CoV-2) screening questionnaire (provided by the study site) at screening or check-in.
33. Have been diagnosed with major depressive disorder or have a history of suicide attempt.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1; Subjects will be asked to continue smoking their UBCs ad libitum for 7 days.
Experimental: Group 2; Subjects will exclusively use 2 mg NP, using at least 3 pouches per day for 7 days.	Other: OTDN Product 1; Mint on!® 2 mg nicotine pouches
Experimental: Group 3; Subjects will exclusively use 4 mg NP, using at least 3 pouches per day for 7 days.	Other: OTDN Product 2; Mint on!® 4 mg nicotine pouches
Experimental: Group 4; Subjects will exclusively use 8 mg NP, using at least 3 pouches per day for 7 days.	Other: OTDN Product 3; Mint on!® 8 mg nicotine pouches
Experimental: Group 5; Subjects will completely stop all tobacco product usage for 7 days.	Other: No Tobacco; subjects completely stop all tobacco product usage for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NNAL Exposure and Change from Baseline	To compare 24-hour urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days	Samples collected on Day -1 (baseline) and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of Exposure (Except NNAL) and Change from Baseline	To compare biomarkers of exposure (BOEs) (except total NNAL) in subjects using NP for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. BOE: NE, 2-AN, 4-ABP, HEMA, CEMA, SPMA, HMPMA, 3-HPMA, 2-HPMA, AAMA, GAMA, 2-MHBMA, 2-OH-Flu, 2-OH-Nap, 1-OH-Phe, 3-OH-B[a]P, 1-OH-Pyr, COHb	Samples collected on Day -1 (baseline) and Day 7
Product Use Behavior	To characterize product use behaviors (such as number of cigarettes smoked per day and number of nicotine pouches used per day).	Data collected on Days 1, 2, 3, 4, 5, 6 and 7

Collaborators and Investigators

• Sponsor: Altria Client Services LLC
• Investigators: Principal Investigator: William J Howitt, MD, QPS Holdings LLC; Principal Investigator: Mark Adams, MD, CKRA

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2021
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): December 27, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: ALCS-REG-20-15-OTDN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No