A Phase 2, Randomized, Double-Blind, Crossover Study to Examine the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Single Doses of TD-4208 in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mylan Inc.
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline
研究概览
简要总结
Thirty-two subjects diagnosed with COPD were enrolled, received each study treatment and completed the follow-up assessments. During each of the four study periods, subjects were admitted to the clinic on Day -1 and housed overnight until after the last spirometry measurement. Serial pulmonary function tests were performed and PK (pharmacokinetics) samples collected up to 25 hours. Subjects were discharged from the clinic on Day 2 after evaluations.
详细描述
Subjects were assigned to one of the 4-treatment sequence groups presented in the table above according to a randomization schedule supplied by the Sponsor before study initiation. The randomization scheme did not include assignments for replacement subjects.
Subjects reported to their respective clinical research unit (CRU) on Admission/Day -1 for pre-randomization procedures and confirmation of eligibility (and continued eligibility for Periods 2 to 4). The unblinded pharmacist prepared and dispensed the nebulizers, according to the randomization schedule for each of the 4 periods. Dosing occurred in the morning, generally between 7 am and 9 am. For Periods 2 to 4, dosing occurred within ±30 minutes of the dosing time established in Period 1.
Study drug was administered in the respective CRU under the supervision of study personnel. Single doses of TD-4208, ipratropium bromide, and placebo were administered in the clinical research unit (CRU) under the supervision of study personnel. Care was taken to avoid eye contact with study drugs. Residual drug solution remaining in the nebulizer (ie, in mL) was measured and recorded.
The investigator or designee was responsible for maintaining accountability records for all study drug(s) in accordance with applicable government regulations and study procedures.
The accountability record included entries for receipt, distribution or dispensing, and destruction of the material(s). Unused and expired study drugs were to be disposed of in accordance with written instructions from the Sponsor.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of moderate stable Chronic Obstructive Pulmonary.
- •Disease with FEV1/FVC <0.7 at screening.
- •Woman of non-childbearing potential.
- •Female participants of childbearing potential must test negative for pregnancy and must be using a highly effective method of birth control during the study and for at least 1 month after completion of study dosing.
- •Female participants must not be breastfeeding.
- •Men must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after completion of study dosing.
- •Current or past smoking history >10 pack-years.
- •Must be capable of performing reproducible spirometry maneuvers.
排除标准
- •History of significant respiratory disease other than COPD, and/ or requires daily long-term oxygen therapy.
- •Exacerbation of COPD, lung infection within 6 weeks prior to study.
- •Start of or change in dose of COPD treatment 4 weeks before study.
- •Daily using of maintenance systemic/inhaled corticosteroids (>1000 microgram of fluticasone propionate equivalent or >5 mg prednisone).
- •Use of bronchodilators or medication for the treatment of COPD, aspirin, anti-inflammatories for a specific time, prior to the first dose or is not willing to abstain from their use for the specified time periods prior to study dose administration.
- •Symptomatic prostrate hypertrophy, bladder neck obstruction, active cancer, narrow angle glaucoma.
- •Clinical significant hypersensitivity to medications.
- •Participants have an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine or other disease that may place participant at risk.
- •Cerebrovascular, cardiovascular disease or abnormal ECG.
- •History of drug or alcohol abuse.
研究组 & 干预措施
Sequence 1
Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg
干预措施: Placebo (Drug)
Sequence 1
Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg
干预措施: TD-4208 700 μg (Drug)
Sequence 1
Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg
干预措施: TD-4208 350 μg (Drug)
Sequence 1
Period 1 = Placebo; Period 2 = TD-4208 700 μg; Period 3 = TD-4208 350 μg; Period 4 = Ipratropium 500 μg
干预措施: Ipratropium 500 μg (Drug)
Sequence 2
Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg
干预措施: Placebo (Drug)
Sequence 2
Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg
干预措施: TD-4208 700 μg (Drug)
Sequence 2
Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg
干预措施: TD-4208 350 μg (Drug)
Sequence 2
Period 1 = TD-4208 700 μg; Period 2 = Ipratropium 500 μg; Period 3 = Placebo; Period 4 = TD-4208 350 μg
干预措施: Ipratropium 500 μg (Drug)
Sequence 3
Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg
干预措施: Placebo (Drug)
Sequence 3
Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg
干预措施: TD-4208 700 μg (Drug)
Sequence 3
Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg
干预措施: TD-4208 350 μg (Drug)
Sequence 3
Period 1 = TD-4208 350 μg; Period 2 = Placebo; Period 3 = Ipratropium 500 μg; Period 4 = TD-4208 700 μg
干预措施: Ipratropium 500 μg (Drug)
Sequence 4
Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo
干预措施: Placebo (Drug)
Sequence 4
Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo
干预措施: TD-4208 700 μg (Drug)
Sequence 4
Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo
干预措施: TD-4208 350 μg (Drug)
Sequence 4
Period 1 = Ipratropium 500 μg; Period 2 = TD-4208 350 μg; Period 3 = TD-4208 700 μg; Period 4 = Placebo
干预措施: Ipratropium 500 μg (Drug)
结局指标
主要结局
Peak Forced Expiratory Volume in One Second (FEV1) Relative to Baseline
时间窗: From predose to 25 hours postdose
次要结局
- Peak Expiratory Flow Rate (PEFR) From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1(12hr and 24hr)
- Area Under the FEV1 vs. Peak FEV1, Time-matched Difference From Placebo(12 hr and 24 hr)
- Area Under the FEV1 vs. Time Curve, Time-matched Difference From Placebo(12 hr and 24 hr)
- Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75), as Related to FEV1(12hr and 24hr)
- Forced Vital Capacity (FVC)(From predose to 25 hours postdose)
- Area Under the Forced Vital Capacity (FVC) vs. Time Curve(0-24 hours)