A Large Simple Safety Study of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 841
- 试验地点
- 69
- 主要终点
- Time From Randomization to Respiratory Death or First COPD Exacerbation Related Hospitalization (Whichever Occurs First).
研究概览
简要总结
This is a multi-center study to evaluate the long-term safety of arformoterol 15 mcg twice daily (BID) in the treatment of subjects with moderate-to-severe COPD. Study participation will consist of a total of 6 visits over approximately 1 year.
详细描述
This is a multi-center, double-blind, randomized, placebo-controlled, parallel-group, outpatient, safety study to evaluate the long-term safety of arformoterol 15 mcg twice daily (BID) in the treatment of subjects with moderate-to-severe COPD. The administration of arformoterol in subjects with moderate to severe COPD will not result in a meaningfully greater incidence of respiratory death and COPD exacerbation -related hospitalizations compared to placebo (nebulized saline and non-long-acting beta2-agonist [LABA] COPD standard of care treatments). This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must give written informed consent, including privacy authorization as well as adherence to concomitant medication withholding periods, prior to participation.
- •Females considered not of childbearing potential must be surgically sterile (total hysterectomy, bilateral salpingo oophorectomy, or tubal ligation) or post-menopausal, which is defined as a complete cessation of menstruation for at least 1 year.
- •Male and female subjects must be at least 40 years old at the time of consent.
- •Subjects must have a pre-established, documented primary clinical diagnosis of non-asthmatic COPD or are referred for diagnosis of non-asthmatic COPD.
- •Subjects must have a baseline FEV1 of ≤50% predicted volume at Visits 1 and 2 (pre-dose).
- •Subjects must have a FEV1 >0.50 L at either Visit 1 or 2 (pre-dose).
- •Subject's respiratory status must be clinically stable.
- •Subjects must have a FEV1/forced vital capacity (FVC) ratio of ≤70% at either Visit 1 or 2 (pre-dose).
- •Subjects must have had at least 1 COPD exacerbation within the last year (defined as initiation or an increase in the dose of oral steroids or antibiotics for the treatment of COPD).
- •Subjects must have a ≥15 pack-year smoking history and a baseline breathlessness severity grade of ≥2 (Modified Medical Research Council [MMRC] Dyspnea Scale Score) at Visit
- •Female subjects ≤65 years of age must have a negative serum pregnancy test conducted at Visit 1 prior to randomization. Females of childbearing potential must be using an acceptable method of birth control.
- •Subjects' overall health must be sufficiently stable to complete the study requirements based on the screening physical examination (defined as the absence of any clinically relevant abnormalities), medical history, 12-lead ECG, and clinical laboratory values (hematology, serum chemistry and urinalysis), and vital signs (heart rate, respiratory rate, and blood pressure) that have been conducted within 30 days of Visit 2 (randomization). If any of the hematology, chemistry, or urinalysis results are not within the laboratory's reference range, then the subject can be included only if the investigator judges the deviations to be not clinically significant.
- •Subjects must have a minimum blood pressure of 105/60 mmHg and a minimum resting pulse of 50 bpm at Screening Visit
- •Subjects who do not meet these criteria at Screening Visit 1 must meet the criteria on the first day of dosing (Day 1) in order to be eligible for the study. Subjects with a medical condition which causes low blood pressure or low heart rate, but, in the opinion of the Principal Investigator or designee the medical condition could resolve, may be rescreened when the condition is resolved.
- •Subjects must be willing and able to complete all study questionnaires and logs reliably.
- •Subjects must be willing and able to comply with study procedures and visit schedule.
- •Subjects must have sufficient understanding of English to complete all questionnaires and logs.
排除标准
- •Female subjects who are pregnant or lactating.
- •Subjects with a history of asthma, with the exception of asthma diagnosed in childhood.
- •Subjects with a blood eosinophil count >5% of total white blood cell count.
- •Subjects with a febrile illness within 3 days before Screening.
- •Subjects with a malignant neoplasm other than non melanomatous basal cell skin cancer. Subjects with a history of malignancy who have been cancer free for 5 years or more may be enrolled.
- •Subjects who are currently using disallowed medications or will be unable to complete the medication washout periods. Subjects taking a prohibited concurrent medication which requires a washout of >30 days may be rescreened when the washout of the prohibited concurrent medication has been met.
- •Subjects with life threatening/unstable respiratory status, including upper or lower respiratory tract infection, within the previous 30 days prior to screening.
- •Subjects who have had a change in dose or type of any medications for COPD within 2 weeks prior to the screening visit. Subjects not on a stable dose of COPD medications may be rescreened after being on a stable dose for at least 14 days
- •Subjects with a chest x ray taken ≤3 months prior to screening that suggests a diagnosis other than COPD (eg, diagnostic of pneumonia, other infection, atelectasis, or pneumothorax or other active/ongoing pulmonary conditions). If there is no chest x ray taken ≤3 months prior to screening, or if recent results are unavailable for review, a chest x ray must be performed prior to visit
- •Subjects with a medical condition that caused the abnormal finding, but, in the opinion of the Principal Investigator or designee the medical condition could resolve, may be rescreened when the condition is resolved
- •Subjects with a positive urine drug test during screening.
- •Subjects with a known history of alcohol abuse may be enrolled in the study if the subject's current alcohol use does not exceed more than 3 alcoholic beverages per day.
- •Subjects whose schedule or travel prevents the completion of all required visits.
- •Subjects who are scheduled for inpatient hospitalization or elective surgery (inpatient or outpatient) during the trial. Subjects may be rescreened when the condition is resolved.
- •Subjects have participated in an investigational drug study and/or any COPD interventional trial within 30 days prior to screening or who are currently participating in another investigational drug study or COPD interventional trial.
- •Subjects with a history of allergic reaction to the study medication or any components of the study medications.
- •Subjects who are study site staff members or relatives of study site staff members directly involved in this study.
- •Subjects with clinically significant cardiac, (Functional Class III and IV; Objective Class C and D by New York Heart Association [NYHA] Functional Classification),hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol.
研究组 & 干预措施
Placebo twice daily
Placebo twice daily by nebulization. All subjects will be dispensed albuterol HFA metered-dose inhaler (MDI) to be used as needed as rescue medication for bronchospasm and acute treatment of COPD symptoms.
干预措施: Placebo (Drug)
Arformoterol 15 mcg twice daily
Arformoterol 15 mcg twice daily by nebulization. All subjects will be dispensed albuterol HFA metered-dose inhaler (MDI) to be used as needed as rescue medication for bronchospasm and acute treatment of COPD symptoms.
干预措施: Arformoterol (Drug)
结局指标
主要结局
Time From Randomization to Respiratory Death or First COPD Exacerbation Related Hospitalization (Whichever Occurs First).
时间窗: 0-12 months
COPD exacerbation: an increase in COPD symptoms that necessitated any change in baseline medication (bronchodilators,anti-inflammatory agents, antibiotics, supplemental oxygen therapy, etc.).Hospitalization: any inpatient admission or any emergency department visit \> 24 hours in duration. Hospice was considered hospitalization.COPD exacerbation related hospitalization: hospitalization that was due to 1) COPD exacerbation or 2) a COPD exacerbation preceded, or occurred concomitantly with the onset of, the event for which the subject was hospitalized.Respiratory-related death: For each death the Primary Investigator designated a 'probable cause', which was the primary condition that precipitated the terminal events that were the immediate cause of death. If a probable cause could not be ascertained, the cause of death was considered 'UNKNOWN'. Cause other than 'UNKNOWN' was categorized as either respiratory or non-respiratory. Deaths of 'UNKNOWN' cause were counted as primary events.
次要结局
- The Incidence of Treatment Emergent AEs(0-12 months)
- SGRQ: Mean Change From Baseline in Total Score(Baseline and on treatment at months 3, 6 and 12 (or early termination))
- Forced Vital Capacity (FVC): Mean Change From Baseline(Baseline and on treatment at months 3, 6, 9 and 12 (or early termination))
- The Incidence of Protocol Defined COPD Exacerbations.(0-12 months)
- The Incidence of All Cause Mortality(0-12 months)
- FEV1: Mean Change From Baseline(Baseline and on treatments at months 3, 6, 9 and 12 (or early termination))
- Percent Predicted FEV1: Mean Change From Baseline(Baseline and on treatments at months 3, 6, 9 and 12 (or early termination))
- Inspiratory Capacity (IC): Mean Change From Baseline(Baseline and on treatment at months 3, 6, 9 and 12 (or early termination))