NCT02919995已完成2 期
A Phase IIa, Randomised, Double Blind, Placebo Controlled, Three Way Crossover Study to Assess the Pharmacokinetics of RPL554 Administered to Adult Patients With Cystic Fibrosis.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Half Life for Each Dose
研究概览
简要总结
This study evaluates two doses of RPL554 and placebo in adult patients with cystic fibrosis. All patients receive all three treatments in a randomised sequence.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- •Male or female aged ≥18 years at the time of informed consent. Females of childbearing potential must have been using a consistent and reliable form of contraception (see Appendix 1) from the last menses before the first study treatment administration, and must commit to continue to do so during the study and for 3 months after the last dose of study treatment.
- •Have a 12-lead ECG recording at screening (Visit 1) and Visit 2 pre-dose showing the following:
- •Heart rate between 45 and 90 beats per minute
- •QT interval corrected for heart rate using Fridericia's formula (QTcF) interval ≤450 msec
- •QRS interval ≤120 msec
- •PR interval ≤220 msec
- •No clinically significant abnormality including morphology (e.g. left bundle branch block, atrioventricular nodal dysfunction, ST segment abnormalities)
- •Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
- •Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum weight of 40 kg.
- •Patients with a genetic diagnosis of CF.
- •Spirometry at screening demonstrating an FEV1 ≥40% and ≤80% of predicted normal.
- •Capable of withdrawing from long acting bronchodilators1 until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study treatment.
- •Clinically stable CF in the 2 weeks prior to randomisation (Visit 2).
排除标准
- •History of cirrhotic liver disease or portal hypertension.
- •CF exacerbation requiring hospitalisation in the month prior to screening (Visit 1) or prior to randomisation (Visit 2).
- •Use of oral or intravenous antibiotics (in additional to usual maintenance therapy) in the 2 weeks prior to screening (Visit 1) or randomisation (Visit 2).
- •Other non-CF related respiratory disorders: Patients with a current diagnosis of active tuberculosis, lung cancer, sarcoidosis, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- •Previous lung resection or lung transplant.
- •History of, or reason to believe a patient has, drug or alcohol abuse within the past 3 years.
- •Received an experimental drug within 3 months or five half-lives, whichever is longer.
- •Patients with a history of chronic uncontrolled disease including, but not limited to, cardiovascular (including arrhythmias), endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological or ophthalmic diseases that the Investigator believes are clinically significant.
- •Documented cardiovascular disease: angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
- •Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening (Visit 1) or will not have fully recovered from surgery, or planned surgery through the end of the study.
- •Infection with nontuberculous mycobacteria, methicillin-resistant Staphylococcus aureus (MRSA), or Burkholderia species.
- •Use of immune-suppression; long term use of prednisolone ≥10 mg/day.
- •History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell).
- •Clinically significant abnormal values for safety laboratory tests (haematology, biochemistry or urinalysis) at screening (Visit 1), as determined by the Investigator.
- •A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
- •Requires oxygen therapy, even on an occasional basis.
- •Pregnancy or lactation (female subjects only).
- •Any other reason that the Investigator considers makes the patient unsuitable to participate. -
研究组 & 干预措施
Higher Dose RPL554
Experimental
Single dose of inhaled 6 mg RPL554
干预措施: RPL554 (Drug)
Lower dose RPL554
Experimental
Single dose of inhaled 1.5 mg RPL554
干预措施: RPL554 (Drug)
Placebo
Placebo Comparator
Inhaled placebo dose
干预措施: Placebo (Drug)
结局指标
主要结局
Half Life for Each Dose
时间窗: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Half life (t1/2) of RPL554
Maximum Plasma Concentration After Each Dose
时间窗: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Maximum plasma concentration (Cmax) after a single dose of RPL554
AUC by Dose
时间窗: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment
Area under the curve (AUC)
Time to Maximum Plasma Concentration After Each Dose
时间窗: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose
Time to maximum concentration (Tmax) after a single dose of RPL554
次要结局
- Breath Samples(8 and 24 hours after treatment)
- ECG 1(Over 8 hours after treatment)
- AUC FEV1(0-4h)(Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose)
- Laboratory Safety Tests 1(Screening and end of study)
- AUC FEV1(0-6h)(Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose)
- Peak FEV1 for Each Treatment(Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment)
- AUC FEV1(0-8h)(pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose)
- Laboratory Safety Tests 3(Screening and end of study)
- Vital Signs 1(Over 8 hours after treatment)
- FVC(Over 24 hours after treatment)
- Laboratory Safety Tests 2(Screening and end of study)
- Vital Signs 2(Over 8 hours after treatment)
- ECG 2(Over 8 hours after treatment)
研究者
研究点 (1)
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