Efficacy and Safety of Taplucainium Chloride Inhalation Powder in Adults with Refractory or Unexplained Chronic Cough: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the effects of **Taplucainium Inhalation Powder (NOC-110)**, administered once daily for 28 days at three dose levels (1 mg, 3 mg, and 6 mg), compared to placebo, on 24-hour cough frequency in adults with **Refractory or Unexplained Chronic Cough**. This is clinically relevant as it aims to address the persistent and often debilitating symptoms associated with chronic cough, which can significantly impact patients' quality of life and may not respond to standard treatments.

Secondary objectives include:

• Evaluating the effects of NOC-110 on awake-cough frequency.
• Assessing the impact of NOC-110 on measures of quality of life.
• Determining the safety and tolerability of NOC-110.

The clinical trial involves a total of **177 participants** diagnosed with **Refractory or Unexplained Chronic Cough**. The study population includes both male and female adults, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on their diagnosis of chronic cough persisting for 12 months or more. The trial includes individuals who are able to provide informed consent and adhere to specified contraceptive guidelines. Both genders are represented, and the study acknowledges the inclusion of a vulnerable population. Participants' general health status is not specified, nor are specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is appropriate for evaluating the effects of Taplucainium Inhalation Powder on cough frequency.

The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy, safety, and tolerability of **Taplucainium Inhalation Powder** in adults with **refractory or unexplained chronic cough**. The trial will assess the effects of the investigational product administered once daily for 28 days at three dose levels: 1 mg, 3 mg, and 6 mg, compared to a placebo. The primary endpoint is the change in 24-hour cough frequency from baseline to Day 28, measured using VitaloJAK® Cough Counts. Secondary endpoints include changes in awake cough frequency, cough severity, urge to cough, and quality of life, as well as the incidence and severity of adverse events.

The trial will span approximately one year, with an estimated recruitment start date of December 31, 2024, and an estimated end date of December 2, 2025. Participants will be involved in the study for a maximum of 28 days, with the possibility of early termination if they experience significant adverse events or fail to adhere to the study protocol. The study visits will include an initial screening visit to confirm eligibility based on criteria such as having a chronic cough for at least 12 months and the ability to provide informed consent. Follow-up visits will occur throughout the treatment period to monitor safety and efficacy, with a final end-of-study visit to assess overall outcomes and collect final data.

Participants will be randomly assigned to receive either the investigational product or placebo, with both the participants and investigators blinded to the treatment allocation to minimize bias. The investigational product, **Taplucainium Inhalation Powder**, is administered via inhalation using a Monodose Dry Powder Inhaler RS01, which is a capsule-based, refillable single-dose device. The placebo is a blend of inhalation-grade lactose with arginine, taste-masked to minimize unblinding. The trial is not classified as a low-intervention study and is conducted under the sponsorship of Nocion Therapeutics, Inc.

The clinical trial involves the administration of **Taplucainium Inhalation Powder**, an experimental medication formulated as an **inhalation powder, hard capsule**. The active substance in this medication is **taplucainium chloride**, a chemical compound also known by its synonyms: 1-benzyl-1-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)azepan-1-ium chloride, NOC-100 chloride, and NTX-1175 chloride. The medication is provided by NOCION THERAPEUTICS, INC. The treatment is administered via **inhalation** using a Monodose Dry Powder Inhaler RS01, a capsule-based refillable single-dose device designed for size 3 capsules. The dosing regimen includes three dose levels: 1 mg, 3 mg, and 6 mg, with a maximum daily dose of 6 mg and a total maximum dose of 168 mg over a 28-day treatment period. The trial aims to evaluate the efficacy, safety, and tolerability of this medication in adults with refractory or unexplained chronic cough.

The study also includes a **placebo** treatment, which is a blend of inhalation-grade lactose with arginine. This placebo is taste-masked to resemble the active ingredient, minimizing the risk of unblinding during the trial. The placebo is administered in a similar manner to the experimental medication, ensuring consistency in the administration process. The use of a placebo allows for a double-blind, placebo-controlled study design, which is essential for accurately assessing the effects of the experimental treatment.

The efficacy of Taplucainium Inhalation Powder (NOC-110) in adults with **Refractory or Unexplained Chronic Cough** will be assessed through a Phase 2b, randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the change in 24-hour cough frequency from baseline to Day 28, measured using VitaloJAK® Cough Counts. Secondary endpoints include changes in awake cough frequency, Cough Severity Visual Analog Scale (CS-VAS), Urge to Cough Visual Analog Scale (UC-VAS), and the Leicester Cough Questionnaire (LCQ) from baseline to Day 28. Additionally, the Patient Global Impressions of Improvement (PGI-I) score at Day 28 and the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) will be evaluated.

Measurements will be collected at baseline and on Day 28, utilizing validated tools such as the VitaloJAK® for cough counts and various visual analog scales for subjective assessments. The study will compare three dose levels of Taplucainium (1 mg, 3 mg, and 6 mg) administered once daily for 28 days against a placebo. The Monodose Dry Powder Inhaler RS01 will be used for the administration of the inhalation powder. Data analysis will focus on the comparison of changes from baseline to Day 28 across the different treatment groups.