Clinical trial NCT01777334 (phase 3, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: umeclidinium/vilanterol 62.5/25 mcg, tiotropium 18 mcg
SMILES: OCC1=C(O)C=CC(=C1)[C@@H](O)CNCCCCCCOCCOCC1=C(Cl)C=CC=C1Cl, [H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1
Eligibility criteria:

        Inclusion Criteria:

          -  Type of subject: Outpatient.

          -  Informed Consent: A signed and dated written informed consent prior to study
             participation.

          -  Age: Subjects 40 years of age or older at Visit 1.

          -  Gender: Male or female subjects.

        A female is eligible to enter and participate in the study if she is of:

        Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including
        any female who is post-menopausal or surgically sterile). Surgically sterile females are
        defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal
        ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year
        with an appropriate clinical profile, e.g. age appropriate, > 45 years, in the absence of
        hormone replacement therapy.

        OR

        Child bearing potential, has a negative pregnancy test at screening, and agrees to one of
        the following acceptable contraceptive methods used consistently and correctly (i.e. in
        accordance with the approved product label and the instructions of the physician for the
        duration of the study - screening to follow-up contact):

          -  Abstinence

          -  Oral Contraceptive, either combined or progestogen alone

          -  Injectable progestogen

          -  Implants of levonorgestrel

          -  Estrogenic vaginal ring

          -  Percutaneous contraceptive patches

          -  Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP
             effectiveness criteria as stated in the product label

          -  Male partner sterilization (vasectomy with documentation of azoospermia) prior to the
             female subject's entry into the study, and this male is the sole partner for that
             subject. For this definition, "documented" refers to the outcome of the
             investigator's/designee's medical examination of the subject or review of the
             subject's medical history for study eligibility, as obtained via a verbal interview
             with the subject or from the subject's medical records.

          -  Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps)
             with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

               -  COPD Diagnosis: An established clinical history of COPD in accordance with the
                  definition by the American Thoracic Society/European Respiratory Society [Celli,
                  2004].

               -  Smoking History: Current or former cigarette smokers with a history of cigarette
                  smoking of >=10 pack-years [number of pack years = (number of cigarettes per day
                  / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10
                  cigarettes per day for 20 years)]. Previous smokers are defined as those who have
                  stopped smoking for at least 6 months prior to Visit 1.

        Note: Pipe and/or cigar use cannot be used to calculate pack-year history

          -  Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a
             pre and post-albuterol/salbutamol FEV1 of FEV1 of <=70% of predicted normal values
             calculated using NHANES III reference equations at Visit 1 [Hankinson, 1999;
             Hankinson, 2010].

          -  Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC)
             at Visit 1.

        Exclusion Criteria:

          -  Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
             during the study.

          -  Asthma: A current diagnosis of asthma.

          -  Other Respiratory Disorders: Known alpha 1 antitrypsin deficiency, active lung
             infections (such as tuberculosis), and lung cancer are absolute exclusionary
             conditions. A subject who, in the opinion of the investigator, has any other
             significant respiratory conditions in addition to COPD should be excluded. Examples
             may include clinically significant bronchiectasis, pulmonary hypertension,
             sarcoidosis, or interstitial lung disease.

          -  Other Diseases/Abnormalities: Subjects with historical or current evidence of
             clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
             immunological, endocrine (including uncontrolled diabetes or thyroid disease) or
             hematological abnormalities that are uncontrolled and/or a previous history of cancer
             in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has
             been resected for cure is not exclusionary). Significant is defined as any disease
             that, in the opinion of the investigator, would put the safety of the subject at risk
             through participation, or which would affect the efficacy or safety analysis if the
             disease/condition exacerbated during the study.

          -  Contraindications: A history of allergy or hypersensitivity to any
             anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
             magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
             hypertrophy or bladder neck obstruction that, in the opinion of the study physician
             contraindicates study participation or use of an inhaled anticholinergic.

          -  Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit
             1.

          -  Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior
             to Screening (Visit 1).

          -  12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at
             Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG)
             which causes the underlying rhythm and ECG to be obscured. Investigators will be
             provided with ECG reviews conducted by a centralized independent cardiologist to
             assist in evaluation of subject eligibility. Specific ECG findings that preclude
             subject eligibility are listed in Appendix 4. The study investigator will determine
             the medical significance of any ECG abnormalities not listed in Appendix 4.

          -  Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour
             period required prior to spirometry testing at each study visit.

          -  Use of certain medications according to defined time intervals prior to Screening
             (Visit 1).

          -  Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed
             for greater than 12 hours a day. As-needed oxygen use (i.e., >=12 hours per day) is
             not exclusionary.

          -  Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use)
             of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.

          -  Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary
             rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the
             maintenance phase of a pulmonary rehabilitation program are not excluded.

          -  Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2
             years prior to Visit 1.

          -  Affiliation with Investigator Site: Is an investigator, sub-investigator, study
             coordinator, employee of a participating investigator or study site, or immediate
             family member of the aforementioned that is involved in this study.

          -  Previous use of study drug: Previous participation in DB2113360 or DB2113374.