A Phase 3, 24-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Efficacy and Safety Study With Open-label Extension of BLU-5937 in Adult Participants With Refractory Chronic Cough Including Unexplained Chronic Cough (CALM-2) - China Extension
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 38
- 主要终点
- Change from Baseline in Vital Sign: Respiratory Rate (breaths per minute) at Week 24
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, parallel-arm, Phase 3 study of BLU-5937 in participants with Refractory Chronic Cough (RCC).
详细描述
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 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study includes a single-blind placebo run-in followed by a double-blind treatment period with centralized randomization identical investigational product presentation and restricted access to treatment assignments except for emergency unblinding. Additionally a study specific masking plan incorporates a masking strategy by restricting access to potentially treatment unblinding data.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
Matching Placebo for BLU-5937 oral dose twice a day.
干预措施: Placebo (Drug)
BLU-5937 25 mg
BLU-5937 oral dose 25 mg twice a day.
干预措施: BLU-5937 (Drug)
BLU-5937 50 mg
BLU-5937 oral dose 50 mg twice a day.
干预措施: BLU-5937 (Drug)
结局指标
主要结局
Change from Baseline in Vital Sign: Respiratory Rate (breaths per minute) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Vital Sign: Body Temperature (degrees Celsius) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Vital Sign: Weight (kilograms [kg]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Male Reproductive Hormone: Total Testosterone (nanomoles per liter [nmol/L]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Male Reproductive Hormones: Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH] (international units per liter [IU/L]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Vital Signs: Systolic and Diastolic Blood Pressure (millimeters of mercury [mm Hg]) at Week 24
时间窗: Baseline, Week 24
24-Hour Cough Frequency
时间窗: Week 24
Assessed using an ambulatory cough monitor
Change from Baseline in Vital Sign: Pulse (beats per minute) at Week 24
时间窗: Baseline, Week 24
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 24
时间窗: Up to Week 24
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 24
时间窗: Up to Week 24
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 24
时间窗: Up to Week 24
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 24
时间窗: Up to Week 24
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 Male Reproductive Hormone: Inhibin B (nanograms per liter [ng/L]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameter: Red Blood Cell (RBC) Count (10^12 cells per liter) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscular Hemoglobin Concentration (MCHC) (grams per liter [g/L]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameter: Hematocrit (percentage) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) (femtoliters [fL]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (picograms per cell [pg/cell]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) (percentage) at Week 24
时间窗: Baseline, Week 24
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 24
时间窗: Baseline, Week 24
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 24
时间窗: Baseline, Week 24
Change from Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase (ALP) and Creatine Kinase (CK) (international units per liter [IU/L]) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct and Indirect Bilirubin, and Creatinine (micromoles per liter) at Week 24
时间窗: Baseline, Week 24
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 24
时间窗: Baseline, Week 24
Change from Baseline in Clinical Chemistry Parameters: Protein and Albumin (grams per liter [g/L]) at Week 24
时间窗: Baseline, Week 24
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 24
时间窗: Baseline, Week 24
Change from Baseline in Clinical Chemistry Parameters: Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) (seconds) at Week 24
时间窗: Baseline, Week 24
Change from Baseline in Electrocardiogram (ECG) Value: Heart Rate (beats per minute) at Week 24
时间窗: Baseline, Week 24
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 24
时间窗: Baseline, Week 24
次要结局
- Change from Baseline in Cough Severity Visual Analogue Scale at Week 24(Baseline, Week 24)
- Percentage of Participants With Greater than or Equal to (>=) 30 mm Reduction From Baseline in Cough Severity Visual Analog Scale at Week 24(Baseline, Week 24)
- Awake Cough Frequency at Week 24(Week 24)
- Percentage of Participants With >= 30 percent (%) Reduction From Baseline in 24-Hour Cough Frequency at Week 24(Baseline, Week 24)
- Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 24(Baseline, Week 24)
- Percentage of Participants With a >= 1.3-point Increase From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 24(Baseline, Week 24)
- Change from Baseline in the Chronic Cough Diary (CCD) Score at Week 24(Baseline, Week 24)
- Percentage of Participants with CCD Response at Week 24(Week 24)