A Randomised, Open, Placebo-controlled 5-way Crossover Trial of Single Doses of Intranasal GSK256066 in Subjects With Seasonal Allergic Rhinitis (SAR).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression
研究概览
简要总结
This current study is planned as a dedicated pharmacodynamic (effect of drug on the body) study to investigate the dose response in rhinitic subjects at doses where GSK256066 has been proven to work (200mcg) or expected to (50mcg) work. This study also aims to investigate the lower end of the predicted therapeutic range.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is healthy.
- •Body mass index less than 29.0 kg/m² , weight range of 55.0kg (females 50kg) to 95.0kg inclusive.
- •They have a history of hayfever (repeated yearly episodes).
- •They have a positive skin prick test for grass pollen at or within the 12 months preceding the screening visit.
- •They have a positive radioallergosorbent test for grass pollen at or within the 12 months preceding the screening visit.
- •non-smokers.
- •They must have a baseline FEV1>80% predicted and a baseline FEV1(maximum recorded value)/ forced vital capacity (FVC) (maximum recorded value)>70%
- •They are capable of giving informed consent
- •They are available to complete all study measurements.
排除标准
- •Pregnant or nursing females.
- •Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception.
- •The subject has structural nasal abnormalities or nasal polyposis.
- •Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
- •The subject has a history of drug or other allergy that may contraindicate participation.
- •The subject has participated in a study with a new molecular entity during the previous 4 months or in any clinical study in the previous 3 months
- •The subject is concurrently participating in another clinical study and is exposed to an investigational or a non-investigational drug or device.
- •The subject has a screening QTc value >450msec, PR interval outside the range 120 to 240msec or an ECG that is not suitable for QT measurements.In addition subjects will be excluded if they have a history of atrial and ventricular arrhythmia.
- •The subject has a supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
- •The subject has donated a unit of blood (450mL) within the previous 3 months or intends to donate within 3 months of completing the study.
- •The subject is currently taking regular (or a course of) medication whether prescribed or not, including steroids, vitamins, and herbal remedies (e.g. St. John's Wort). Paracetamol (<2g/day) and occasional as needed use of short-acting beta agonists is permitted.
- •Past or present disease which may affect study. outcome
- •The subject regularly, or on average, drinks more than 4 units of alcohol per day - where 1 unit = ½ pint of beer (284mL), or 1 glass of wine (125mL), or 1 measure of spirit (25mL).
- •The subject is at risk of non-compliance with the study procedures/restrictions.
- •The subject has Hepatitis B, Hepatitis C, or HIV virus.
结局指标
主要结局
Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression
时间窗: Day 1
The effect of GSK256066 on ribonucleic acid (RNA) levels indicative of Phosphodiesterase-4 (PDE4) inhibition in nasal scrape samples and on protein biomarkers of PDE4 inhibition in lavage samples was evaluated. Nasal lavage and scrapes were taken 2 to 3 hour post morning dose; bilateral nasal lavage was conducted before the scrape. Nasal scrape samples were taken from alternate nostrils. The novel RNA markers presented are cAMP responsive element modulator (CREM), dual specificity phosphatase 1(DUSP1), fos-like antigen 2(FOSL2), insulin receptor substrate 2 (IRS2), nuclear receptor subfamily 4, group A, member 2 (NR4A2), Phosphodiesterase-4A (PDE4A), Regulator of G-protein signalling 1 (RGS1), Serine/threonine protein kinase SNF1 like kinase (SNF1LK). Nasal lavage cytospins were stained with a SNF1LK specific monoclonal antibody by indirect immunofluorescence. Adjusted Geometric Mean and Standard error logs are presented.
次要结局
- Mean Forced Expiratory Volume in One Second (FEV1)(Up to 9 weeks)
- Mean Heart Rate Over Study Period(Up to 9 weeks)
- Time to Maximum Observed Plasma Drug Concentration (Tmax) and Time to Last Observed Plasma Drug Concentration (Tlast) of GSK256066(Pre -dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)
- AUC (0-last) of Active Metabolite GSK614917(Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)
- Change From Baseline in Electrocardiogram (ECG) Values(Baseline (Day 1) to 9 weeks)
- Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)(Up to 9 weeks)
- Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period(Up to 9 weeks)
- Nasal Lavage Concentrations of GSK256066(Day 1)
- Number of Participants With Hematology Values of Potential Clinical Concern(Up to 9 weeks)
- Number of Participants With Clinical Chemistry Values of Potential Clinical Concern(Up to 9 weeks)
- Area Under the Plasma Drug Concentration Versus Time Curve (AUC0-last) of GSK256066(Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)
- Cmax of Active Metabolite GSK614917(Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)
- Tmax and Tlast of Active Metabolite GSK614917(Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)
- Mean Levels of Total Vasodilator Stimulated Phosphoprotein (VASP) Protein, Phosphorylated(Phospho)157 VASP (pVASP) and phospho239 VASP in Lavage Cells(Day 1)
- Maximum Observed Plasma Drug Concentration (Cmax) of GSK256066(Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1)