A Randomised, Double-Blind (Sponsor-Unblind), Placebo Controlled, Cross-Over Study to Investigate the Efficacy, Effect on Cough Reflex Sensitivity, Safety, Tolerability and Pharmacokinetics of Inhaled GSK2339345 in Patients With Chronic Idiopathic Cough Using an Aqueous Droplet Inhaler
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A)
研究概览
简要总结
This study is designed to evaluate the effect of GSK2339345 relative to placebo on the number of coughs in patients with Chronic Idiopathic Cough (CIC) administered by an Aqueous Droplet Inhaler (ADI). The primary aim is to investigate the efficacy of GSK2339345 on reducing objective cough frequency in CIC patients. The secondary aim of this study is to investigate the efficacy of GSK2339345 in inhibiting a hypertussive cough response elicited by capsaicin and citric acid in CIC patients which have a hyperresponsive cough reflex.
Following the screening visit, all eligible subjects will attend the unit for dosing at Visits 1-7. At Visits 1, 2 and 3 (Part A of the study), subjects will receive two doses of either GSK2339345 or placebo, 4 hours apart and will undergo 8 hours of cough monitoring. At Visits 4 and 5 (Part B of the study) and Visits 6 and 7 (Part C of the study), subjects will be administered a single dose of either GSK2339345 or placebo. Subjects will then undergo capsaicin (Part B) or citric acid (Part C) tussive challenge and will undergo cough monitoring for 1 hour post dose.
The maximum study duration will be approximately 11 weeks, including 3 weeks screening and 2 weeks follow-up. Approximately 30 patients will be randomised into the study, such that approximately 24 patients complete dosing and critical assessments.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A
Subjects will receive treatment A (placebo) or treatment B (GSK2339345) in 3 visits of part A (one treatment per visit) in one of the following four sequences: ABA, ABB, BAA, and BAB.
干预措施: GSK2339345 (Drug)
Part A
Subjects will receive treatment A (placebo) or treatment B (GSK2339345) in 3 visits of part A (one treatment per visit) in one of the following four sequences: ABA, ABB, BAA, and BAB.
干预措施: Placebo (Drug)
Part B
Subjects will receive treatment A or treatment B in 2 visits of part B (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 microliter (mcL) of a capsaicin solution of strength ranging from 0.49 micromolar (mcM) to 1000 mcM, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 4 and 5.
干预措施: GSK2339345 (Drug)
Part B
Subjects will receive treatment A or treatment B in 2 visits of part B (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 microliter (mcL) of a capsaicin solution of strength ranging from 0.49 micromolar (mcM) to 1000 mcM, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 4 and 5.
干预措施: Placebo (Drug)
Part C
Subjects will receive treatment A or treatment B in 2 visits of part C (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 mcL of a citric acid solution of strength ranging from 0.03 to 4.0 M, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 6 and 7.
干预措施: GSK2339345 (Drug)
Part C
Subjects will receive treatment A or treatment B in 2 visits of part C (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 mcL of a citric acid solution of strength ranging from 0.03 to 4.0 M, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 6 and 7.
干预措施: Placebo (Drug)
结局指标
主要结局
Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A)
时间窗: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Total cough count (8 hours \[hr\] of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first four hours starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Number of coughs in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts recorded post dose of every treatment i.e. placebo or GSK2339345 1000mcg was reported.
Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A)
时间窗: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first 4-hrs starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Transient cough was the total number of coughs experienced in the two mins from the start of the first inhalation of a dose. Number of coughs excluding transient cough in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts excluding transient cough recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.
次要结局
- Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C(Pre-dose and 5min to 1 hr after each dose administered in Parts A, B and C (up to 8 Weeks))
- Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Hematocrit Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Corpuscle Volume Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Red Blood Cell Count Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Transient Cough Counts at the Indicated Time Points in Part A(0-4 hr, 4-8 hr, 0-8 hr post each dose at Visits 1, 2 and 3 in Part A (up to 8 weeks))
- Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A)(From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses(From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses(From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)(From the start of study treatment and until the follow-up contact (up to 8 Weeks))
- Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C(Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr post each dose administered in Parts A, B and C (up to 8 weeks))
- Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Troponin I Values at the Indicated Time Points in Part A(Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks))
- Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C(Pre-dose and 30 min post each dose administered in Parts A, B and C (up to 8 Weeks))
- Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A(From 2 min -2 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 8 weeks))
- Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses(From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A)(Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A))
- Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A)(Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A))
- Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A)(Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A)(Up to 8 hours post-dose in Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Mean Cough Counts by 15 Min Epoch in Part A(Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A)(Prior to first dose and 1hr post second dose at Visits 1, 2 and 3 in Part A (up to 3 weeks))
- Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B)(After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 4 and 5 in Part B (up to 2 weeks))
- Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C)(After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 6 and 7 in Part C (up to 2 weeks))
- CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B)(After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks))
- CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C)(After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks))
- CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B)(After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks))
- CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C)(After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks))
- Mean Heart Rate at the Indicated Time Points in Parts A, B and C(Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after each dose administered in Parts A, B and C (up to 8 weeks))
- Mean Body Temperature at the Indicated Time Points in Parts A, B and C(1 hr post the second dose administered in Part A and 1 hr post each dose administered in Parts B and C (up to 8 Weeks))