NCT04027439已完成2 期
A Phase II, Randomized Study to Assess the Pharmacokinetics, Safety and Pharmacodynamics of Single and Repeat Doses of RPL554 Administered by Dry Powdered Inhaler in Patients With COPD
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
- 37
- 试验地点
- 1
- 主要终点
- Part B: Change From Baseline in Peak FEV1 (Over 4 Hours)
研究概览
简要总结
The purpose of this study is to investigate 5 doses of RPL554 and placebo, administered by dry powder inhaler (DPI), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
详细描述
The study will consist of two parts. Part A is a parallel group, placebo-controlled single dose study to ascertain the Pharmacokinetics (PK) profile, safety and bronchodilator effect of RPL554 administered via dry powder inhaler (DPI). Five of the 6 treatment arms will be double-blind and one will be single-blind (due to the different number of capsules administered). Part B is a placebo-controlled, complete block cross-over, repeat dose study to assess the bronchodilator effect of repeat doses of RPL554 delivered via a DPI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（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.
- •For males, not to donate sperm and either be sexually abstinent or use contraception as specified by the protocol. For females, be of non-childbearing potential or use a highly effective form of contraception
- •12-lead ECG with heart rate between 45 and 90 beats per minute, QTcF ≤450 msec for males, and ≤ 470 msec for females, QRS interval ≤120 msec and no clinically significant abnormality including morphology
- •Capable of complying with all study restrictions and procedures including ability to use the DPI correctly.
- •Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
- •COPD diagnosis for 1 year [prior to screening
- •Ability to perform acceptable and reproducible spirometry.
- •Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
- •FEV1/Forced Vital Capacity (FVC) ratio of ≤0.70
- •FEV1 ≥40 % and ≤80% of predicted normal
- •≥150 mL increase from pre-bronchodilator FEV1
- •Clinically stable COPD in the 4 weeks prior to Screening and during the period between Screening and Part A.
- •A chest X-ray showing no abnormalities, which are both clinically significant and unrelated to COPD.
- •Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
- •Current and former smokers with smoking history of ≥10 pack years.
- •Capable of withdrawing from long acting bronchodilators for the duration of the study, and short acting bronchodilators for 8 hours prior to dosing.
排除标准
- •A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- •COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to Part A.
- •A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to Part A.
- •Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or RPL
- •Evidence of cor pulmonale or clinically significant pulmonary hypertension.
- •Other respiratory disorders
- •Previous lung resection or lung reduction surgery.
- •Use of immunosuppressive therapy, including oral corticosteroids
- •Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
- •History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
- •Received an experimental drug within 30 days or five half lives, whichever is longer.
- •Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.
- •Documented cardiovascular disease, including any history of arrhythmias, angina, recent (<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening
- •Use of non-selective oral β-blockers.
- •Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
- •A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
- •Required use of oxygen therapy, even on an occasional basis.
- •History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell).
- •Clinically significant abnormal values for safety laboratory tests (hematology, biochemistry, viral serology or urinalysis) at Screening, as determined by the Investigator. In particular, alanine aminotransferase or aspartate aminotransferase cannot be more than twice the upper limit of normal.
- •Any other reason that the Investigator considers makes the patient unsuitable to participate.
研究组 & 干预措施
Part A: RPL554
Active Comparator
Placebo controlled, parallel group single dose. Five of the 6 treatment arms will be double-blind and one will be single-blind
干预措施: Placebos (Drug)
Part B: RPL554
Active Comparator
Double-blind, placebo-controlled, complete block cross-over
干预措施: Placebos (Drug)
结局指标
主要结局
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours)
时间窗: Day 7
Change from Baseline FEV1 to Peak FEV1 (over 4 hours) on Day 7
Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12)
时间窗: Day 1
RPL554 Plasma pharmacokinetics AUC0-12 (Area under the Curve) after single dose
Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)
时间窗: Day 1
RPL554 Plasma pharmacokinetics Half-life concentration after a single dose
Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC 0-t)
时间窗: Day 1
RPL554 Area under the curve at maximum concentration after a single dose
次要结局
- Part A: Change From Baseline in Average FEV1 (Over 4 Hours)(Day 1)
- Part A: Safety and Tolerability / Hematology Safety Assessments(Day 1)
- Part B: Safety and Tolerability / ECG - QTcF(Day 7)
- Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate(Day 7)
- Part B: Change From Baseline in Peak Pulse Rate (Day 1)(Day 1)
- Part A: Change From Baseline in Average FEV1 (Over 12 Hours)(Day 1)
- Part A: Safety and Tolerability / Blood Chemistry Safety Assessments(Day 1)
- Part A: Safety and Tolerability / Urinalysis Safety Assessments(Day 1)
- Part B: Safety and Tolerability / Hematology Safety Assessments(Day 7)
- Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure(Day 7)
- Part A: Change From Baseline in Peak FEV1 (Over 4 Hours)(Day 1)
- Part A: Safety and Tolerability / Supine Vital Signs - Blood Pressure(Day 1)
- Part A: Safety and Tolerability / ECG - QTcF(Day 1)
- Part B: Change From Baseline in Peak Pulse Rate (Day 7)(Day 7)
- Part B: Change From Baseline in Average FEV1 (Over 12 Hours)(Day 1)
- Part B: Change From Baseline in Trough FEV1(Day 7)
- Part B: Change From Baseline in Average FEV1 (Over 4 Hours)(Day 1)
- Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action)(Day 1)
- Part A: Safety and Tolerability / Supine Vital Signs - Pulse Rate(Day 1)
- Part A: Safety and Tolerability / ECG - Heart Rate(Day 1)
- Part B: Change From Baseline in Average FEV1 (Over 4 Hrs)(Day 7)
- Part B: Change From Baseline in Peak FEV1 (Over 4 Hours)(Day 1)
- Part B: Safety and Tolerability / Blood Chemistry Safety Assessments(Day 7)
- Part B: Safety and Tolerability / Urinalysis Safety Assessments(Day 7)
- Part B: Safety and Tolerability / ECG - Heart Rate(Day 7)
- Part B: RPL554 Plasma Pharmacokinetic Parameter (Cmax)(Day 7)
- Part B: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12h)(Day 7)
- Part B: RPL554 Plasma Pharmacokinetic Parameter (Tmax)(Day 7)
研究者
研究点 (1)
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