Refractory Chronic Cough. MedDRA version: 20.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: GRC 17536 potassium powder for inhalation
Product Code: GRC 17536 potassium
Pharmaceutical Form: Inhalation powder, hard capsule
Current S
Sponsors
Glenmark Pharmaceuticals SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with refractory chronic cough are defined as: cough lasting longer than 8 weeks; and refractory after routine assessment as per British Thoracic Society (BTS) guidelines despite adequate treatment of potential aggravating factors or removal of obvious precipitating factors. Adequate treatment equals treatment at the dose and duration recommended by the BTS guidelines; 2. Males and females of non child-bearing potential (post menopausal/surgically sterile only) of =18 yrs and = 75 yrs; 3. Non-smokers or ex-smokers for at least 12 months prior to study; 4. Patients with documented normal chest X-ray or CT scan (historical data up to 1 year may be used); normal spirometry; vitals and clinical laboratory tests within the reference ranges or clinically acceptable to the investigator; 5. Patients who are able and willing to provide voluntary written informed consent. 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 48 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with non-chronic or acute cough or cough with purulent sputum or cough with sputum >10 mL/day; 2. Patients with a cough severity threshold 1.5x upper limit of normal (ULN)]; 7. Concomitant disease or condition that could interfere with the conduct of the study, or for which the treatment could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease; 8. Patients who have had a change in medication (taken for associated cough conditions) 2 weeks preceding randomisation; 9. Current diagnosis of active epilepsy or any active seizure disorder requiring therapy with antiepileptic drug(s); or patients on anti-epileptic treatment; 10. Patients who are not willing or whose partners are not willing to use appropriate method of contraception from the time of the first dose until 3 months after the last dose of GRC 17536; or intend to donate sperm during this period; (See section 10.3.5 Contraception) 11. Patients with clinically significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (other than neuropathy), psychiatric, haematological, renal, or dermatological disease, or any other medical condition, or clinically significant abnormalities in laboratory test results or ECG that according to investigator’s medical judgment could potentially affect a patient's safety or study outcome. 12. Patients who received inducers of CYP3A4 enzymes (including but not limited to the drugs listed in excluded medications) within 4 weeks prior to the first dosing; 13. Patients who donated a unit of blood (450 ml) in the 3 months prior to first dosing or who intend to donate in the 3 months after the last scheduled study visit. 14. Patients who received angiotensin-converting-enzyme (ACE) inhibitors within 3 months prior to randomisation or are on treatment;15. Patients with a supine systolic blood pressure (SBP) =160 mmHg and/or a supine diastolic blood pressure (DBP) =100 mmHg; 16. Patients with documented or suspected or current history of alcohol abuse (intake of more than 24 units of alcohol per week) or drug abuse; 17. 12-lead ECG demonstrating QTcF>450 ms at screening; 18. Patients who have received any investigational drug (including GRC 17536) in any clinical trial within 3 months prior to randomisation, or who are on extended follow-up; 19. Patients who cannot communicate reliably with the investigator; or who are unlikely to co-operate wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of GRC 17536 on 24 hr cough frequency using the Leicester cough monitor in patients with refractory chronic cough.; Secondary Objective: 1. To evaluate safety and tolerability of GRC 17536; 2. To evaluate the effect of GRC 17536 on cough-specific Quality of Life (QOL) using the Leicester cough questionnaire (LCQ); 3. To evaluate the effect of GRC 17536 on cough severity, intensity and urge to cough using a Visual Analogue Scale (VAS); 4. To evaluate the effect of GRC 17536 on cough reflex sensitivity to citric acid (in a subset of patients); 5. To evaluate the effect of GRC 17536 on change in cough severity and cough frequency between visits using a Global Rating of Change Questionnaire (GRCQ); 6. To evaluate the effect of GRC 17536 on cough symptoms using a day and night Cough Symptom Score (CSS); 7. To evaluate the effect of GRC 17536 on generic QOL using an EQ-5D-5L questionnaire; 8. To study the pharmacokinetics (PK) of GRC 17536 (in a subset of patients). ;Primary end point(s): Change in log 24 hr cough frequency from baseline to End of Treatment (EOT) between GRC 17536 and placebo.;Timepoint(s) of evaluation of this end point: Baseline to end of 4 week (End of treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety and tolerability of GRC 17536; 2. Change in the following parameters from baseline to EOT between GRC 17536 and placebo; • Day time and night time cough frequency; • LCQ score; VAS Scores (severity, intensity and urge to cough); GRCQ (severity and frequency); CSS (day and night symptoms) and EQ-5D-5L; • Change in cough reflex sensitivity to citric acid; 3. PK parameters (Cmax AM, Tmax AM, AUC(0-24), AUC(0- t, AM); RacAUC(0-t)) ;Timepoint(s) of evaluation of this end point: Baseline to end of 4 week (End of treatment) | — |
Countries
United Kingdom
Contacts
Public ContactPrajakt Barde
Glenmark Pharmaceuticals SA
Outcome results
None listed