Safety Study of Arformoterol Tartrate Inhalation Solution in Chronic Obstructive Pulmonary Disease (COPD) Subjects
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Arformoterol; Placebo
Intervention description: Arformoterol Tartrate Inhalation Solution 15 mcg twice daily (BID) for a duration of one year; Placebo inhalation solution, twice daily (BID) for a duration of one year.
Intervention MeSH terms: Formoterol Fumarate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 841.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Chronic obstructive pulmonary disease (COPD); respiratory; long-acting beta agonist (LABA)

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 2.

          -  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 1. 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.

        Exclusion Criteria:

          -  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 2. 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.