Clinical trial NCT01551316 (phase 1, status: completed)
Conditions: chronic obstructive pulmonary disease
ICD codes: J44.9, J44.1, J44.0
Drugs: mn-221, placebo
SMILES: CN(C)C(=O)COC1=CC=C2CC[C@@H](CC2=C1)NC[C@H](O)C1=CC=C(O)C(CCO)=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female 40-75 years of age, inclusive;

          -  History of physician-diagnosed (e.g., by clinical history, >15-pack year history of
             smoking, physical examination, and spirometry) COPD treated for ≥ 3 months prior to
             Visit 1 Pre-Screening;

          -  FEV1 ≥ 30% and < 80% predicted and FEV1/FVC ratio < 0.7 at Visit 1 Pre-Screening and
             Visit 2 Screening;

          -  Negative urine pregnancy test for all females unless the subject is post-menopausal (≥
             24 months of spontaneous amenorrhea) or surgically sterile (hysterectomy, bilateral
             ovariectomy or bilateral tubal ligation);

          -  Negative urine drug screen for cocaine, phencyclidine (PCP), methamphetamine;

          -  Negative alcohol breath test;

          -  Electrocardiogram (ECG) without serious abnormality and with QTcB and QTcF < 460
             milliseconds (msec);

          -  Ability to wash-out of concomitant LABA and Theophylline, if ongoing, for 7-8 days
             (i.e., Visit 2 Screening through 5-Day Treatment Period).

          -  Legally effective written informed consent obtained prior to starting any study
             procedures.

          -  Subject willing and able to comply with the protocol and procedures, as judged by
             Investigator.

        Exclusion Criteria:

          -  Sustained release methylxanthine (e.g. Theophylline) or long acting beta agonists ≤ 48
             hours prior to treatment start (Day 1);

          -  Acute exacerbation of COPD requiring emergency treatment ≤ 30 days of screening or
             hospitalization ≤ 60 days of Visit 2 Screening;

          -  Antibiotic therapy for respiratory infection ≤ 15 days of Visit 2 Screening;

          -  Presence of active respiratory disease such as pneumonia and acute exacerbation of
             chronic bronchitis;

          -  Hypokalemia defined as a potassium level <3.0 mmol/L at Visit 2 Screening. note:
             Subjects <3.0 mmol/L may be re-screened at Visit 2 Screening after receiving potassium
             replacement therapy;

          -  Significant clinical laboratory abnormality that, in the opinion of the Investigator,
             may put the subject at risk;

          -  Significant renal, hepatic, endocrine, neurologic or other systemic disease that, in
             the opinion of the Investigator, may put the subject at undue risk;

          -  Uncontrolled hypertension (defined as a blood pressure ≥ 170/100 mm Hg at Visit 1
             Pre-Screening) and/or uncontrolled angina, uncontrolled diabetes, uncontrolled
             congestive heart failure (CHF), uncontrolled serious arrhythmia;

          -  Myocardial infarction within 6 months of treatment start;

          -  Pregnant or lactating females;

          -  Participation in another clinical study with an investigational drug within 30 days of
             Visit 1 Pre-Screening;

          -  Patients with home oxygen requirements.

          -  A known allergy to excipients of the MN-221 drug product;

          -  A known allergy to other beta agonists;

          -  Currently on medication/s that are recognized to have risk of Torsades de Pointes