Placebo-controlled, Single and Multiple Dose Study in Healthy Volunteers and Refractory Chronic Cough Patients to Assess the Safety, Tolerability, and Pharmacokinetics of Two Formulations of NTX-1175

Exclusion Criteria

• •Participants who meet any one of the following criteria will be deemed ineligible for participation in the study:
• •1. Is found to have positive test for SARS-CoV-2 at Screening or Check-in Day -1, whether or not this was accompanied by the clinical symptoms of COVID-19.
• •2. Current smoker or individuals who have given up smoking within the past 6 months prior to screening, or those with \>20 pack-year smoking history (Part 2)
• •3. Current diagnosis of chronic obstructive pulmonary disease (COPD), bronchiectasis, unexplained pulmonary fibrosis, or asthma (Part 2).
• •4. History or presence of alcohol or drug use disorder, per Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), within the past 2 years prior to screening.
• •5. Current opiate/opioid use in the past 7 days prior to screening, or medical history of opiate/opioid use disorder.
• •6. Unable to refrain from the use of:
• •1. Gabapentin, pregabalin, and/or amitryptline or other tricyclics within 4 weeks prior to screening and throughout the study (Part 2)
• •2. Chronic, systemic corticosteroid use within 4 weeks prior to screening and throughout the study (Part 2).
• •3. Inhalers including long-acting and short acting beta 2-agonists (LABA and SABA), and inhaled corticosteroids (ICS) within 8 weeks prior to screening and throughout the study.
• •4. Lidocaine or related compounds of any form within 14 days prior to screening and throughout the study (Part 2).
• •5. Medication or remedies to aid sleeping 14 days prior to screening and throughout the study (Part 2).
• •6. Angiotensin-converting enzyme (ACE)-inhibitor within 12 weeks prior to screening and throughout the study (Part 2).
• •7. Antitussives 7 days prior to screening and throughout the study (Part 2).
• •8. Speech and language therapy for rCC within 4 weeks prior to screening and throughout the study (Part 2).
• •9. Food and beverages containing alcohol for 24 hours prior to screening (Part 2).
• •7. History or presence of cardiac dysfunction including arrhythmia, bundle branch block; Wolff Parkinson White syndrome, recent thromboembolic event, prolonged PR (≥220 msec), QRS (≥120 msec), QTcF interval (≥450 msec \[males\] or ≥470 msec \[females\]) or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at Screening.
• •8. Positive results at Screening for HIV, HBsAg, or HCV (participants successfully treated for HCV may be permitted at the discretion of the Investigator).
• •9. Supine blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg (Part 1), or greater than 160/95 mmHg (Part 2) at Screening. Vital signs may be repeated twice.
• •10. Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening. Vital signs may be repeated twice.
• •11. History of asthma or COPD (Part 1).
• •12. Forced expiratory volume in 1 second/ forced vital capacity (FEV1/FVC) \< lower limit of normal (LLN) per Global Lung Health Initiative normative dataset at Screening.
• •13. Had symptoms of any significant acute illness, including symptoms of COVID-19 within 30 days before the start of the study (time of first dose), as determined by the Investigator.