Refractory Chronic Cough (RCC). MedDRA version: 20.0 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000016024
Conditions
Interventions
Product Name: AX-8
Pharmaceutical Form: Orodispersible tablet
CAS Number: 1401555-39-2
Current Sponsor code: AX-8
Other descriptive name
Sponsors
Axalbion SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Females and males between 18 and 80 years of age inclusive 2. Have a diagnosis of RCC or unexplained cough for at least one year (see BTS guidelines in Appendix C of the protocol) and associated upper airway symptoms (throat or laryngeal irritation, tickling, dryness or discomfort) of at least 8-week duration. Regular pattern of cough with expected daily episodes of cough that occur throughout the day, as ascertained by medical history. 3. Chest radiograph or CT Thorax within the last 5 years not demonstrating any abnormality considered to be significantly contributing to the chronic cough in the opinion of the Principal Investigator and Axalbion SA Medical Monitor. 4. At Screening have a score of = 40mm on the Cough Severity VAS. 5. At Baseline have a score of = 40mm on the Cough Severity VAS. 6. All female subjects who are of childbearing potential must practice highly effective contraception (i.e. pregnancy prevention method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Prior treatment with AX-8. 2. Hypersensitivity or intolerance to AX-8 or other TRPM8 agonists (e.g. menthol, menthol-like compounds), or any of the excipients of AX-8 ODT. 3. Current smoker or individuals who have given up smoking within the past 12 months or ex-smoker with > 20 pack-years. 4. FEV1/FVC 2x the upper limit of normal (ULN) during screening. 12. Clinically significant abnormality of renal function, defined as e-GFR < 60 ml/min. 13. Positive test for any drug-of-abuse (unless this can be explained by the subject’s medication). 14. History of malignancy within 5 years prior to the Baseline Visit (Day 0), with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin. 15. History of a major psychiatric condition (including major depressive disorder, bipolar disorder, or schizophrenia), suicidal ideation, or suicide attempt. 16. Known active hepatitis infection. 17. Known history of human immunodeficiency virus (HIV) infection. 18. Presence of any medical condition or disability that, in the investigator’s opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject, including clinically significant ECG abnormalities during screening, baseline (Day 0) or pre-dose (Day 1). 19. Currently pregnant or breastfeeding female subject, or male subject with a pregnant or breastfeeding partner. 20. Females of childbearing potential who are unable or unwilling to practice highly effective contraception (pregnancy prevention).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effectiveness of AX-8 for the treatment of RCC and associated upper airway symptoms after one dose of treatment in reducing awake cough frequency compared to baseline, for the purpose of planning a future randomised controlled trial.; Secondary Objective: •To evaluate the duration of effectiveness of AX-8 after 1 dose of treatment in reducing hourly objective cough frequency over a 24-hour period •To evaluate the effectiveness of AX-8 in: o Reducing the cough severity measured by a Visual Analog Scale (VAS) o Reducing the throat irritation and the urge to cough measured by a Visual Analog Scales (VAS) o Inducing a sensation of throat cooling (VAS) •To assess the safety and tolerability of AX-8 in patients with RCC. ;Primary end point(s): The primary efficacy endpoint is the change from Baseline in awake objective cough frequency after 1 dose of treatment. ; Timepoint(s) of evaluation of this end point: Baseline - Day -1 to Day 1 (24 hours) Treatment - Day 1 to Day 2 (24 hours) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Cough frequency: Baseline: Day-1 to Day1(24 hours), Treatment: Day1 to Day2(24 hrs) • Cough Severity, Urge-to-cough, Throat irritation VAS: - Baseline: pre-cough monitor –30 mins, post-cough monitor +1, +2, +3, +4, +5, +6 hrs - Treatment: pre-dose –30 mins, post-dose +1, +2, +3, +4, +5, +6 hrs and Day2 for last 24 hrs - Day7-14(follow-up) • Throat Cooling VAS: - Day1: pre-dose –30 mins, post-dose: +30 mins, +1, +1.5, +2, +2.5, +3, +4, +5, +6 hrs. Day2 for last 24 hrs. • Global Rating of Change Scale: - Day1: +4 hrs post dose, Day2 and Day7-14 visits Safety Endpoints: • TEAEs and SAEs: Day 1 post dose onwards • Clinical laboratory: Screen and Day 7-14 visit • Vital sign and ECG: Screen, Day0, Day1 pre-dose, +4 hrs post-dose and Day7-14 visits ; Secondary end point(s): Key Secondary Efficacy Endpoints • Change from Baseline in hourly objective cough frequency over a 24-hour monitoring period; • Proportion of subjects with = 30% reduction in 24-hour cough frequency per hour; • Proportion of subjects with = 30% reduction in awake cough frequency per hour; • Change from Baseline in Cough Severity VAS; • Change from Baseline in urge-to-cough VAS; • Global Rating of Change Scale (GRCS). • Change in Throat Irritation and Throat Cooling VAS; Safety Endpoints: • Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs); • Changes in clinical laboratory parameters following study drug exposure; • Changes in vital sign and ECG parameters following study drug expo | — |
Countries
United Kingdom
Contacts
Public ContactMarco Rüedi
Axalbion SA
Outcome results
None listed