Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS

Inclusion Criteria:

• Adult, both sexes, aged ≥ 40 years.

• Patient has read, understood, and signed the written informed consent form (ICF),which has received IEC or IRB approval.

• Patient with body mass index (BMI) 17.6-40.0 kg/m2 and body weight > 50 kg (male) or > 40 kg (female). Checked at V1 and V2.

• Patient has a CIG smoking history ≥ 10 years.

• Patient has been smoking ≥ 10 commercially available and/or roll-your-own CIG/day onaverage (no brand restriction) for at least the last year (based on self-reporting).Smoking status will be verified by Urine cotinine test (UCOT) ≥200 ng/mL.Intermittent CIG smoking abstinence, with or without Smoking Cessation Treatmentduring these attempts, not exceeding 10 days total within the past year will beallowed. Checked at V1 and V2.

• Patient has been advised to quit smoking, informed of smoking risks and of cessationprograms as per SoC at V2, and is not willing to quit CIG use for the studyduration. Checked at V1 and V2.

• Patient agrees to be randomized into one of the two study arms. Checked at V2.

• Patient with confirmed COPD via spirometry performed at V1 (FEV1/FVC <70%,post-bronchodilator (-BD)) and COPD severity classified by the Global Initiative forChronic Obstructive Lung Diseases (GOLD) as GOLD 2 or 3 (30%≤ FEV1 < 80% predicted, -BD) with presence of chronic bronchitis (cough and mucus most of the days for >three months a year for the two consecutive years prior to the screening visit).Checked at V2.

• Patient has cough frequency of ≥ 10 cough/hour during daytime from objective countsensor applied at V1, used to verify eligibility at V2. (Daytime is defined asoccurring between 07:00:00 and 22:59:59, based on the local time zone of the sitewhere the patient is assessed.)

Exclusion Criteria:

• Patient who self-report concomitant daily use of inhaled cannabis or any type ofnicotine containing products other than CIG within the last year.

• Patient with COPD (moderate or severe) exacerbation that has not resolved accordingto the GOLD standard (e.g., requirement of additional therapy) or investigator'sdiscretion. Checked at V1 and V2.

• Patient with currently active cancer or history of any cancer within the last 5years prior to V1, except for those with basal cell carcinoma of the skin.

• Patient with acute worsening symptoms of chronic bronchitis or other activerespiratory or systemic infections that have not resolved. Checked at V1 and V2.

• Patient with medical condition(s) that would jeopardize his(her) safety in thecontext of this study (e.g., safety laboratory parameters, abnormal ECG) or with acondition that would jeopardize study results (e.g., gastroesophageal reflux disease (GERD), heart failure, severe chronic lung emphysema, active symptomatic hay fever),as per Investigator's discretion. Checked at V1 and V2.

• Patient is legally incompetent, physically, and/or mentally incapable of givingconsent (e.g., emergency situation, under guardianship, in a social or sanitaryestablishment, prisoner or involuntarily incarcerated, unable to read).

• Patient with a history of asthma.

• Employee of the investigational site or any other party involved in the study, ortheir first-degree relatives (parent, child, spouse).

• Current or former employee of the tobacco or e-cigarette industry or their 1st-degree relatives.

• Patient with active or history of alcohol and/or drug abuse within the past year.

• Patient with positive serological tests for human immunodeficiency virus (HIV) 1/2,hepatitis B or C (Hep B/C).

• Patient with any concomitant issues (e.g., medical, psychiatric, and/or socialreason) that, as per Investigator's discretion, would place the study patient at anunacceptable risk for participation in the study.

• Patient who participated in any trial (for investigational medicine, or other typeof intervention) that may have interfered with COPD disease progression and symptoms (including cough and dyspnea) within the last three months as per investigator'sdiscretion.

• Patient using any systemic (injectable or oral) corticosteroids (acute or chronictreatments) or oxygen therapy in the last 2 months excluding short term use for aCOPD exacerbation.

• Patient currently being treated with angiotensin-converting enzyme (ACE) inhibitorsor opioids, or those who have used ACE inhibitors within 4 weeks or opioids within 1week prior to screening. Checked at V1 and V2.

• Patient treated with biologic therapies for COPD (e.g., Dupilumab) in the last 6months.

• Female patient is pregnant, breastfeeding or lactating, or anticipating becomingpregnant withing the duration of the study. Checked at V1 and V2.

• Female of childbearing potential who is capable of getting pregnant, defined as afemale patient who does not agree to use an acceptable method of effectivecontraception during the entire study, a female patient that is not surgicallysterilized (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) for atleast 6 months or postmenopausal (postmenopausal females must have no menstrualbleeding for at least 1 year). Checked at V1 and V2.