Cough, Refractory Chronic Cough
Conditions
Keywords
Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory, Cough, Chronic Cough
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-arm, Phase 3 study of BLU-5937 in participants with Refractory Chronic Cough (RCC).
Detailed description
The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained chronic cough) at 12 weeks.
Interventions
DRUGBLU-5937
Oral administration of BLU-5937 Tablets
DRUGPlacebo
Oral administration of matching placebo for BLU-5937 Tablets
Sponsors
Bellus Health Inc. - a GSK company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Capable of giving signed informed consent * Refractory chronic cough (including unexplained chronic cough) for at least one year * Women of child-bearing potential must use a highly effective contraception method during the study and for at least 14 days after the last dose
Exclusion criteria
* Current smoker/vaper (all forms of smoking and inhaled substances, including, cannabis/tobacco smoke and nicotine vapors) or individuals who have given up smoking within the past 6 months, or those with \>20 pack-year smoking history * Diagnosis of chronic obstructive pulmonary disease, bronchiectasis, chronic bronchitis, cystic fibrosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis, uncontrolled asthma, or other significant or progressive airway/respiratory disorder that might affect cough based on clinician assessment * Respiratory tract infection within 4 weeks before screening * Laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection at screening * History of malignancy in the last 5 years * History of alcohol or drug abuse within the last 3 years * Has a positive serologic test for human immunodeficiency virus (HIV), hepatitis B virus surface antigen, or hepatitis C virus. * Previous participation in a BLU-5937 trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in ECG Value: PR Interval, QT Interval, RR Interval, QRS Interval, and Corrected QT Interval Using Fridericia's Formula (QTcF) (milliseconds) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-Glutamyl Transferase (GGT) (units per liter [U/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase (ALP) and Creatine Kinase (CK) (international units per liter [IU/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct and Indirect Bilirubin, and Creatinine (micromoles per liter) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Calcium, Magnesium, Bicarbonate, Glucose, and Blood Urea Nitrogen (BUN) (millimoles per liter [mmol/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Protein and Albumin (grams per liter [g/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameter: Estimated Glomerular Filtration Rate (eGFR) (milliliters per minute per 1.73 meters squared [mL/min/1.73 m^2]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Clinical Chemistry Parameters: Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) (seconds) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Electrocardiogram (ECG) Value: Heart Rate (beats per minute) at Week 52 | Baseline, Week 52 | — |
| 24-Hour Cough Frequency | Week 12 | Assessed using an ambulatory cough monitor |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 52 | Up to Week 52 | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator. |
| Number of Participants with Adverse Events of Medical Interest (AEMIs) up to Week 52 | Up to Week 52 | An AEMI is an event of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring is appropriate. The following are AEMIs for this study: taste disturbance, oral hypoesthesia, oral paresthesia, and new or worsening findings of the cornea. |
| Number of Participants with Study Treatment Discontinuation due to AEs and SAEs up to Week 52 | Up to Week 52 | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator. |
| Number of Participants with AEs and SAEs Leading to Study Withdrawal up to Week 52 | Up to Week 52 | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator. |
| Change from Baseline in Vital Signs: Systolic and Diastolic Blood Pressure (millimeters of mercury [mm Hg]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Vital Sign: Pulse (beats per minute) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Vital Sign: Respiratory Rate (breaths per minute) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Vital Sign: Body Temperature (degrees Celsius) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Vital Sign: Weight (kilograms [kg]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Male Reproductive Hormone: Total Testosterone (nanomoles per liter [nmol/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Male Reproductive Hormones: Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH] (international units per liter [IU/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Male Reproductive Hormone: Inhibin B (nanograms per liter [ng/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameter: Red Blood Cell (RBC) Count (10^12 cells per liter) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscular Hemoglobin Concentration (MCHC) (grams per liter [g/L]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameter: Hematocrit (percentage) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) (femtoliters [fL]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (picograms per cell [pg/cell]) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) (percentage) at Week 52 | Baseline, Week 52 | — |
| Change from Baseline in Hematology Parameters: White Blood Cell (WBC) Count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) and Platelet Count (10^9 cells per liter) at Week 52 | Baseline, Week 52 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Greater than or Equal to (>=) 30 mm Reduction From Baseline in Cough Severity Visual Analogue Scale at Week 12 | Baseline, Week 12 | Assessed by Cough Severity Visual Analogue Scale \[VAS\] by the participant on a 100 mm visual analogue scale where higher scores indicate greater severity. |
| Awake Cough Frequency at Week 12 | Week 12 | Assessed using an ambulatory cough monitor |
| Percentage of Participants With >= 30 percent (%) Reduction From Baseline in 24-Hour Cough Frequency at Week 12 | Baseline, Week 12 | Assessed using an ambulatory cough monitor |
| Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | Baseline, Week 12 | The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the patient responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the impact of cough on 3 domains: physical, psychological, and social. Domain scores range from 1-7, and the total score ranges from 3 - 21; a higher score indicates a better quality of life. |
| Percentage of Participants With a >= 1.3-point Increase From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | Baseline, Week 12 | The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the patient responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the impact of cough on 3 domains: physical, psychological, and social. Domain scores range from 1-7, and the total score ranges from 3 - 21; a higher score indicates a better quality of life. |
| Change from Baseline in the Chronic Cough Diary (CCD) Score at Week 12 | Baseline, Week 12 | The CCD is a participant-completed daily diary used to assess chronic cough. The CCD score ranges from 0 to 16, with a higher score indicating worse symptoms. |
| Percentage of Participants with CCD Response at Week 12 | Week 12 | Percentage of participants with CCD response will be summarized. |
| Change from Baseline in Cough Severity Visual Analogue Scale at Week 12 | Baseline, Week 12 | Assessed by Cough Severity Visual Analogue Scale \[VAS\] by the participant on a 100 mm visual analogue scale where higher scores indicate greater severity. |
Countries
Argentina, Belgium, Canada, Colombia, France, Hungary, India, Israel, Netherlands, Poland, South Africa, Spain, United Kingdom, United States
Outcome results
None listed