Clinical trial NCT02579850 (phase 3, status: completed)
Conditions: chronic obstructive pulmonary disease (copd)
ICD codes: G91.1, I42.1, N11.1, J05.0, G47.33, J44.9, N13.8
Drugs: chf 5993 + ultibro matched placebo, ultibro + chf 5993 matched placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, C[N+]1(C)CCC(C1)OC(=O)C(O)(C1CCCC1)C1=CC=CC=C1
Eligibility criteria:

        Inclusion :

          1. Male and female ≥ 40 years

          2. Severe or very severe COPD diagnosed for at least 12 months

          3. Current smokers or ex-smokers who quit smoking at least 6 months prior to screening
             visit, with a smoking history of at least 10 pack years

          4. Post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator
             FEV1/FVC ratio < 0.7

          5. Documented history of at least one exacerbation in the 12 months

          6. Patient under double therapy for at least 2 months prior to screening. Double therapy
             will be defined by treatment with any of the following:

             Orally inhaled corticosteroid (ICS) and (long-acting beta2-agonist) LABA ICS and
             long-acting muscarinic antagonist (LAMA) Orally LABA and LAMA Monotherapy with LAMA
             for at least 2 months prior to screening

          7. Symptomatic patient at screening with a CAT score ≥ 10.

          8. Cooperative attitude and ability to use correctly the inhalers, the spacer AeroChamber
             Plus (only to patients who are using a spacer), the electronic devices with COPD
             questionnaire.

        Exclusion :

          1. Pregnant or lactating women and all women physiologically capable of becoming pregnant
             UNLESS are willing to use one or more of the reliable methods of contraception

          2. Patient with a current clinical diagnosis of asthma with a physician-judged need for
             inhaled or oral corticosteroid therapy

          3. Patient requiring use of the following medications:

             Course of systemic steroids > 3 days for COPD exacerbation in the 4 weeks prior to
             screening Course of antibiotics for COPD exacerbation > 7 days in the 4 weeks prior to
             screening Phosphodiesterase-4 inhibitor in the 4 weeks prior to screening Use of
             antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening

          4. COPD exacerbation requiring prescription of systemic corticosteroids and/or
             antibiotics or hospitalization during the run-in period

          5. Patient treated with non-cardioselective β-blockers in the month preceding the
             screening or during the run-in period.

          6. Patient treated with long-acting antihistamines unless taken at stable regimen at
             least 2 months prior to screening and to be maintained constant during the study or if
             taken as needed

          7. Patient requiring long term (at least 12 hours daily) oxygen therapy for chronic
             hypoxemia

          8. Known respiratory disorders other than COPD which may impact the efficacy of the study
             drug

          9. Patient who have clinically significant cardiovascular condition

         10. Patient with atrial fibrillation (AF): Paroxysmal atrial fibrillation, Persistent,
             Long standing or Permanent

         11. Abnormal and clinically significant 12-lead ECG that results in active medical problem
             which may impact the safety of the patient

         12. Patient whose ECG shows QTcF >450 ms for males or QTcF >470 ms for females at
             screening visit are not eligible (not applicable for patient with pacemaker)

         13. Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy
             or bladder neck obstruction would prevent use of anticholinergic agents

         14. History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of
             the excipients contained in any of the formulations used in the trial which may raise
             contra-indications or impact the efficacy of the study drug

         15. Clinically significant laboratory abnormalities indicating a significant or unstable
             concomitant disease which may impact the efficacy or the safety of the study drug

         16. Patients with hypokalaemia (serum potassium <3.5 mEq/L or 3.5 mmol/L) or uncontrolled
             hyperkalaemia

         17. Unstable concurrent disease which may impact the results of the study

         18. Patients with any history of malignancy likely to result in significant disability or
             likely to require significant medical or surgical intervention within the next six
             months (after V1) or with malignancy for which they are currently undergoing radiation
             therapy or chemotherapy

         19. History of alcohol abuse or substance/drug abuse within 12 months prior to screening
             visit

         20. Participation in another clinical trial if investigational drug was received less than
             8 weeks prior to screening visit