A Placebo-controlled, Double-blind (Sponsor Open), Randomized, Crossover Study to Assess the Efficacy, Safety, and Tolerability of GSK2798745 in Participants With Chronic Cough
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Total Cough Counts During Day Time Hours Following 7-days of Dosing
研究概览
简要总结
GSK2798745 is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel blocker being investigated for the treatment of chronic cough. This is a multi-center, randomized, placebo-controlled, double-blind, two-period crossover study with a purpose to evaluate efficacy and safety of GSK2798745. Each subject will have 2 treatment periods, and will be randomized to one of the following treatments in each period: A) Placebo matching to GSK2798745 once daily for 7 days. B) 4.8 milligrams (mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 once daily for 6 days. There will be a washout period of 14 to 21 days between the treatment periods. A maximum of 48 subjects will be enrolled in the study and the total duration of participation in the study will be maximum of 10 and a half weeks including follow-up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
All study staff involved in clinical assessments (which includes the investigator, sub-investigators, other site staff), and the subject will be blinded to the treatment allocated to individual subjects.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- •Chronic idiopathic cough for >=1 year (before screening), defined as: a cough that is unresponsive to at least 8 weeks of targeted treatment, or a cough for which no objective evidence of an underlying trigger has been determined, despite medical investigations.
- •No significant findings on chest imaging (chest X-ray [CXR] or Computed tomography scan) within 12 months before screening (subjects with an abnormal CXR within 12 months, from a temporary process, will be allowed to participate if a repeat CXR is normal).
- •Forced expiratory volume in one second (FEV1) >=80% of the predicted normal value (at screening), or documented evidence of FEV1 >=80% within the 6 months before screening.
- •Score of >=40 millimeters (mm) on the Cough Severity Visual Analogue Scale (VAS) at Screening.
- •Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18 to 40 kilogram per meter square (kg/m^2) (inclusive) at screening.
- •A male participant must agree to follow the contraception requirements stated in the protocol from the time of first dose of study treatment until 2 weeks after last dose of study treatment, and refrain from donating sperm during this period.
- •A female participant is eligible to participate if she is not of childbearing potential.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
排除标准
- •History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the medical monitor, make the subject unsuitable for inclusion in this study.
- •History or current evidence of chronic productive cough.
- •History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the 6 months before screening.
- •Active ulcer disease or gastrointestinal bleeding at the time of screening (positive fecal occult blood test [FOBT] at screening).
- •History of stroke or seizure disorder within 5 years of screening.
- •Respiratory tract infection within 6 weeks of screening.
- •Subject who, in the investigator's opinion, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g. Type 4 or 5 on the Columbia Suicidality Severity Rating Scale (C-SSRS) in the last 6 months (assessed at screening).
- •Alanine transferase (ALT) > twice the upper limit of normal (ULN) at screening.
- •Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •QT interval corrected (QTc) >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block at screening.
- •Use of a listed prohibited medication within the restricted timeframe relative to the first dose of study treatment.
- •Use of a strong inhibitors or inducers of cytochrome P450 (CYP) 3A or pglycoprotein.
- •Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months of screening.
- •Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- •Current enrollment or past participation within the 3 months before screening in any clinical study involving an investigational study treatment or any other type of medical research.
- •Positive human immunodeficiency virus (HIV) antibody test at screening.
- •Presence of Hepatitis B surface antigen (HBsAg) at screening.
- •Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment.
- •Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
- •Cardiac troponin at screening > ULN for the assay.
- •History of alcohol abuse within 6 months of screening, in the opinion of the investigator.
- •Current smoker or history of smoking within the 6 months before screening, or a cumulative history of >= 20 pack years. Pack years = (Number of cigarettes smoked/day/20) x (Number of years smoked)
- •Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study.
研究组 & 干预措施
Treatment Sequence AB
Subjects will receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days).
干预措施: GSK2798745 (Drug)
Treatment Sequence AB
Subjects will receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days).
干预措施: Placebo (Drug)
Treatment Sequence BA
Subjects will receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days).
干预措施: GSK2798745 (Drug)
Treatment Sequence BA
Subjects will receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days).
干预措施: Placebo (Drug)
结局指标
主要结局
Total Cough Counts During Day Time Hours Following 7-days of Dosing
时间窗: Up to 10 hours post-dose on Day 7 of each treatment period
Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.
次要结局
- Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)(Baseline (Day -1) and Day 8 of each treatment period)
- Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine(Baseline (Day -1) and Day 8 for each treatment period)
- Change From Baseline Values for Clinical Chemistry Parameter: Total Protein(Baseline (Day -1) and Day 8 of each treatment period)
- Change From Baseline Values for Hematology Parameter: Hematocrit(Baseline (Day -1) and Day 8 of each treatment period)
- Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 45 days)
- Number of Participants With Abnormal Values of Cardiac Troponin(Up to 45 days)
- Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count(Baseline (Day -1) and Day 8 of each treatment period)
- Change From Baseline in Heart Rate(Baseline (pre-dose on Day 1) and Day 8 of each treatment period)
- Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea(Baseline (Day -1) and Day 8 of each treatment period)
- Change From Baseline Values for Hematology Parameter: Hemoglobin(Baseline (Day -1) and Day 8 for each treatment period)
- Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count(Baseline (Day -1) and Day 8 for each treatment period)
- Change From Baseline in Temperature(Baseline (pre-dose on Day 1) and Day 8 of each treatment period)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Baseline (pre-dose on Day 1) and Day 8 of each treatment period)
- Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)(Baseline (Day -1) and Day 8 for each treatment period)
- Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(Baseline (pre-dose on Day 1) and Day 8 of each treatment period)
- Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)(Baseline (Day -1) and Day 8 of each treatment period)
- Change From Baseline Values for Hematology Parameter: Reticulocytes(Baseline (Day -1) and Day 8 for each treatment period)
- Number of Participants With Abnormal Urinalysis Data(Up to Day 8)