This study will characterize the dose response of TD-4208 after 7 days of dosing in subjects with Chronic Obstructive Pulmonary Disease (COPD).

Inclusion Criteria:

1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at randomization).

2. Subject:

   • Has an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) <0.7 at screening; and
   • Has a post-bronchodilator FEV1 at screening of between 30% and 80% (inclusive) of the predicted normal value.

3. Subject demonstrates at screening at least a 120 mL increase in FEV1 within 1 hour of receiving 500 µg of ipratropium bromide from a PARI LC Sprint® nebulizer.

4. Females of non-childbearing potential. All male subjects 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.

5. Subject (or care giver) is able to properly prepare and administer study medication.

6. Subject is willing and able to give written informed consent to participate.

Exclusion Criteria:

1. Subject has had a COPD exacerbation or lung infection within 6 weeks before randomization.
2. Subject has had an initiation of treatment, or a change in dose, of an inhaled or oral corticosteroid, or long-acting beta2 agonist (LABA), or long-acting muscarinic antagonist (LAMA) within 4 weeks before the qualifying ipratropium bromide response test.
3. Subject is taking daily maintenance inhaled/systemic corticosteroids (>1000 μg of fluticasone propionate equivalent or ≥10 mg prednisone).
4. Subject has an uncontrolled hematologic, immunologic, renal, neurologic, hepatic, endocrine, or other disease or condition based on information gathered from the medical history, physical examination, or laboratory findings that might place the subject at undue risk or potentially compromise the results or interpretation of the study.
5. Subject has a history of significant cerebrovascular disease, coronary artery disease, or cardiac arrhythmias. Subject has a history (or family history) of congenital prolonged QTc (corrected QT interval) syndrome or has an abnormal clinically significant electrocardiogram (ECG) at screening, including QTcB (QT interval corrected for heart rate using Bazett's formula) value >450 msec (males) or >470 msec (females); or shows evidence of clinically significant rhythm abnormality.
6. Subject has a known hypersensitivity to TD-4208 or similar drug class.
7. Subject has a history of alcoholism or drug abuse within 2 years prior to screening.

13 weeks

The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.