Refractory chronic cough MedDRA version: 21.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Code: S-600918
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not established
CAS Number: N/A
Current Sponsor code: S-600918
Other descriptive name: S-600918
Concentration unit:
Sponsors
Shionogi B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male or female outpatient =18 to =80 years of age at the time of signing the informed consent form. -Has refractory chronic cough lasting for at least 1 year prior to Visit 1, defined as: insufficient improvement in cough after treatment for the underlying condition(s) causing the cough OR unexplained cough for which an underlying condition has not been determined -With severity of cough assessed as =40 mm on the Visual Analog Scale (VAS) at both Visit 1 and Visit 2. -With cough count =10 times per hour based on the 24- hour cough count recording at Visit 1. (Results will be available by Visit 2; no calculation is necessary). -If female, agreement to use one of the following contraceptive methods from screening until 14 days after the last dose of study drug UNLESS the patient is surgically sterile by hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy or tubal ligation with appropriate documentation of such surgery or postmenopausal (defined as at least 12 months of spontaneous amenorrhea in women >45 years of age). Progestogen-only oral hormonal contraception (where inhibition of ovulation is not the primary mode of action), male or female condom with or without spermicide, cap, diaphragm, or sponge with spermicide. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 360 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: - Currently smokes or uses potentially irritating inhalational agents (eg, e-cigarettes, smokeless cigarettes, vaping); stopped smoking or using potentially irritating inhalational agents within the last year; or has a smoking history of 20 pack-years or more. - Has chronic obstructive pulmonary disease (COPD) or, as defined in the Global Initiative for Asthma (GINA) 2019, has uncontrolled asthma symptoms (excluding cough). - Has a clinically unstable medical condition. - History of or ongoing significant psychiatric disorder. - History of respiratory tract infection or significant change in lung function or a pulmonary condition in the last 4 weeks. - History of malignancy in the last 5 years. - History of severe drug allergy. - History of alcohol or drug abuse in the last year or currently uses any form of marijuana or illicit drugs. - With any finding on a chest x-ray or chest CT scan (performed not more than 1 year prior to Visit 1 after onset of chronic cough at Visit 1) that could be considered the cause of chronic cough or indicative of lung disease. (If a chest x- ray or chest CT scan needs to be performed, results will be available by Visit 2.) (Note: Patients with abnormal chest image findings not considered to be the cause of chronic cough are eligible to participate.) - Has systolic blood pressure > 160 mm Hg or diastolic blood pressure > 90 mm Hg. - Received S-600918 previously. - Received an investigational drug in the last 3 months. - Received an angiotensin converting enzyme (ACE) inhibitor in the last 3 months or requires such treatment. - Has a positive serologic test for human immunodeficiency virus (HIV) antigen or antibody, hepatitis B virus surface antigen, or hepatitis C virus ribonucleic acid (RNA). - If female, pregnant or trying to become pregnant or breastfeeding. COVID-19 related Measure is provided in Protocol Version 3.1 page no. 36 (Exclusion Criteria, Point no. 19)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 4;Main Objective: To determine the optimal dose of S-600918 in patients with refractory chronic cough by evaluating the change from baseline in 24-hour cough frequency (coughs per hour) with S-600918 compared with placebo;Primary end point(s): The primary efficacy endpoint is the ratio of the number of coughs per hour in 24 hours (based on cough counts recorded by the cough monitor) after administration of study drug for 4 weeks to that at baseline.;Secondary Objective: To compare the efficacy of S-600918 to that of placebo in patients with refractory chronic cough based on the following measurements: - Number of coughs per hour while awake - Number of coughs per hour while asleep - Severity of cough as assessed on the Visual Analog Scale (VAS) - Leicester Cough Questionnaire (LCQ) - International Consultation on Incontinence Modular Questionnaire-Short Form (ICIQ SF) - Short-Form (36) Health Survey (SF-36), version 2 - Patient Global Impression of Change (PGIC) To evaluate the safety of S-600918 in patients with refractory chronic cough. To assess the pharmacokinetics (PK) of S-600918 and its metabolite (S-600918 acyl glucuronide) in patients with refractory chronic cough. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •A reduction from baseline in the number of coughs per hour in 24 hours by =30%, =50%, and =70% • The ratio of the number of coughs per hour while awake after administration of study drug for 4 weeks to that at baseline and a reduction by =30%, =50%, and =70% • The ratio of the number of coughs per hour while asleep after administration of study drug for 4 weeks to that at baseline • The change from baseline in weekly cough severity as assessed on the VAS (electronic tablet) • The change from baseline through Day 7 in daily cough severity as assessed on the VAS (eDiary) • The change in LCQ and achievement of an increase (ie, improvement) of =1.3 points • The change in ICIQ-SF • The change in SF-36 • PGIC;Timepoint(s) of evaluation of this end point: Week 4 | — |
Countries
Czech Republic, Japan, Poland, Ukraine, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Shionogi B.V.
Outcome results
None listed