Single-dose, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Bronchodilatory Effects of Glycopyrrolate Inhalation Solution (GIS) Using a High Efficiency Nebulizer in Patients With COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 主要终点
- Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study
研究概览
简要总结
The study assessed the safety and ability of several doses of an orally inhaled medicine [ie, Glycopyrrolate Inhalation Solution = GIS] to improve airflow in the lungs when delivered with an electronic eFlow nebulizer system in patients with Chronic Obstructive Pulmonary Disease (COPD). The study was conducted in 12 patients in 2 parts. Part 1 was designed to find the once-a- day GIS dose that produced the highest improvement in lung airflow. Part 2 tested the GIS dose with the highest improvement in lung airflow and a placebo (ie, no drug) delivered by a general purpose nebulizer. The airflow improvements of the same GIS dose were compared between the two nebulizer systems to determine what effect the device had on GIS delivery.
详细描述
In Part I, 12 subjects were randomly allocated to one of 2 cohorts, running in parallel. The 6 cohort 1 subjects received 25 mg and then 200 mg during their treatment periods 1 and 2, respectively. The 6 cohort 2 subjects received 75mg, 500mg, and 1000 mg during their treatment periods 1, 2, and 3, respectively. During Part II of the study, the same 12 subjects from Part I were randomized to receive either 200 mg jet or placebo in a 1:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, 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
- •Male and female patients aged 40 through 75 years, inclusive
- •A clinical diagnosis of COPD according to the GOLD guidelines
- •Current smokers or ex-smokers with at least 10 pack-year smoking history (e.g., at least 1 pack/day for 10 years, or 10 packs/day for 1 year)
- •Post-bronchodilator FEV1 40-80% of predicted normal
- •Post-bronchodilator FEV1/FVC ratio < 0.70
- •Improvement in FEV1 >12% (minimum 150 mL) following inhalation of ipratropium bromide
- •Ability to perform reproducible spirometry according to the ATS/ERS guidelines
- •If female and of childbearing potential, must have had a negative pregnancy test and was not lactating at the Screening Visit, and was using one of the following acceptable means of birth control throughout the study:
- •Post-menopausal for at least two years
- •Surgically sterile
- •Oral contraceptives (taken for at least one month prior to the Screening Visit)
- •Approved implantable or injectable contraceptives (e.g., Norplant®, Depo-Provera® or equivalent)
- •Barrier methods (e.g., condoms with spermicide)
- •Intrauterine device (i.e., IUD)
- •Vasectomy of male partner
- •Non-heterosexual life style
- •Willing and able to provide written informed consent
排除标准
- •Current evidence or recent history of any clinically significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the patients at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infraction, hypertension, arrhythmia, diabetes, neurological or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities.
- •Recent history of an exacerbation of airway disease within 3 months or need for increased treatments for COPD within 6 weeks prior to the Screening Visit.
- •Regular use of daily oxygen therapy.
- •Use of systemic (e.g., intramuscular or intravenous) steroids within 3 months prior to the Screening Visit
- •Respiratory tract infection within 6 weeks prior to the Screening Visit
- •History of tuberculosis, bronchiectasis or other non-specific pulmonary disease
- •History of urinary retention or bladder neck obstruction type symptoms
- •History of narrow-angle glaucoma
- •Current or recent history (previous 12 months) of excessive use or abuse of alcohol
- •Current evidence or history of abusing legal drugs or the use of illegal drugs or substances
- •History of hypersensitivity or intolerance to aerosol medications
- •Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit
研究组 & 干预措施
Glycopyrrolate Inhalation Solution 200mg Jet
Glycopyrrolate Inhalation Solution 200 μg via jet nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution 200mg Jet (Drug)
Glycopyrrolate Inhalation Solution 500mg
Glycopyrrolate Inhalation Solution 500 μg via eFlow nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution 500mg (Drug)
Glycopyrrolate Inhalation Solution 25mg
Glycopyrrolate Inhalation Solution 25 μg via eFlow nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution 25mg (Drug)
Glycopyrrolate Inhalation Solution 75mg
Glycopyrrolate Inhalation Solution 75 μg via eFlow nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution 75mg (Drug)
Glycopyrrolate Inhalation Solution 200mg
Glycopyrrolate Inhalation Solution 200 μg via eFlow nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution 200mg (Drug)
Glycopyrrolate Inhalation Solution1000mg
Glycopyrrolate Inhalation Solution 1000 μg via eFlow nebulizer, once daily
干预措施: Glycopyrrolate Inhalation Solution1000mg (Drug)
Placebo 0.5 mL
Placebo 0.5 mL via jet nebulizer, once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study
时间窗: 30 hrs post dose
Vital signs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study assessment. The clinical significance of each out of normal range vital sign parameter was determined by the investigator during the study.
Number of Subjects With Treatment Emergent SAEs
时间窗: 0-47 days
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.
Number of Subjects Who Died
时间窗: 0-47 days
Number of Subjects Who Discontinued Due to AE
时间窗: 0-47 days
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.
Percentage of Subjects With Treatment Emergent AEs
时间窗: 0-47 days
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.
Number of Subjects With Treatment Emergent AEs
时间窗: 0-47 days
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.
Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study
时间窗: post study follow-up assessment (Day 47)
Clinical safety lab parameters were collected at screening and at the post study follow-up assessment. The clinical significance of each out of normal range laboratory parameter was determined by the investigator during the study.
Number of Subjects With Clinically Significant ECG Parameters Reported During the Study
时间窗: 30hr post dose
ECGs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study follow-up assessment.
次要结局
- Peak FEV1 (Change From Baseline )(0 to 4hr)
- Peak FEV1 (Percent Change)(0 to 4hr)
- Tmax Time to Maximum Observed Plasma Concentration(0 to 12 hours post dose)
- Trough FEV1 (Change From Baseline)(24hr post dose)
- AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration(0 to 12 hourr post dose)
- AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity(0 to 12 hours post dose)
- FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline)(0 to 24hr post dose)
- Cmax Maximum Observed Plasma Concentration(0 to 12 hours post dose)
- t1/2 Plasma Half-life(0 to 12 hours post-dose)