| Eligibility |
Inclusion Criteria:
Patients must meet all the following:
1. Male or female patients aged 40 to 75 years of age with a body mass index
= 17 and = 35 kg/m2.
2. Female patients must be either of non-childbearing potential or if of childbearing
potential use a highly effective birth control method (See Section 9.4.1).
3. Male patients with female partners of childbearing potential must be vasectomised with
documented medical assessment of the surgical success or use highly effective
contraception together with their female partner(s) (See Section 9.4.1).
4. Female patients must agree not to donate ova/oocytes during the study and for 30 days
after the last dose of IMP.
5. Male patients must agree not to donate semen during the study and for 90 days after
the last dose of IMP.
6. Confirmed diagnosis by a physician of COPD with symptoms compatible with COPD for at
least 1 year prior to screening.
7. Severity of Disease: patients who conform to the current severity classification for
GOLD Grade II/III disease in terms of post-bronchodilator spirometry at screening:
Post-salbutamol FEV1/FVC ratio of < 0.70. Post-salbutamol FEV1 = 40 % and = 80 % of
predicted normal values (based on the Global Lung Function Initiative [GLI-2012][1]).
8. Current or previous tobacco smoker with a smoking history of = 10 pack years (1 pack
year = 20 cigarettes smoked per day for 1 year or equivalent).
9. Vital signs recorded from automated blood pressure equipment within the following
normal ranges: Blood pressure; systolic value of 90 mmHg to 160 mmHg, diastolic value
of 60 mmHg to 90 mmHg and pulse rate = 60 and
=100 beats per minute at screening and prior to randomisation.
10. Able to provide written Informed Consent Form (ICF) prior to participation in any
study-related activities, and to comply with the requirements of the study.
11. Able to perform technically acceptable spirometry at screening.
12. Able to produce a sputum sample of adequate quality at either the Screening or
Baseline visit prior to randomisation.
13. Able to demonstrate the correct inhalation technique for use of the delivery device
and to generate sufficient peak inspiratory flow (PIF) (at least 40 L/min) using the
In-Check DIAL device at screening and prior to randomisation.
Exclusion Criteria:
Patients who meet any of the following are not eligible:
1. Upper or lower respiratory tract infection within 6 weeks prior to screening or prior
to randomisation.
2. COPD exacerbation requiring oral steroids and/or antibiotics, within the 6 weeks prior
to screening or prior to randomisation.
3. Clinically significant abnormal laboratory values at screening that, in the opinion of
the investigator would make the patient inappropriate for the study or put the patient
at undue risk, specifically liver function tests (LFTs: aspartate aminotransferase
[AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], total
bilirubin) >3 x upper limit of normal (ULN); hemoglobin <10 gm/dL; absolute neutrophil
count (ANC) <1000; white blood cells (WBC) >20,000; Platelets <100,000 and >500,000;
prothrombin time (PT) >14 seconds.
4. QTcF of >450 msec in males or >470 msec in females on any of the three individual ECG
measurements at screening or prior to randomisation.
5. History of drug or alcohol abuse within the past 2 years prior to screening or prior
to randomisation.
6. History of regular alcohol consumption within 6 months prior to screening or prior to
randomisation defined as an average weekly intake of >21 units for males, or >14 units
for females, where one unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of
beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
7. Positive alcohol breath test result at screening or prior to randomisation.
8. Positive urine drugs of abuse test result (unless in the opinion of the investigator
this can be explained by the patient's current medications) at screening or prior to
randomisation; unexpected or unexplained positive results may require discussion with
Sponsor.
9. Current users of e-cigarettes and those who have used these products within one month
prior to screening or between screening and randomisation.
10. Known sensitivity to the study drug or any of the excipients of the formulation, or
history of clinically significant sensitivity to any agent that, in the opinion of the
investigator, would make participation in the study inadvisable.
11. Donated blood or blood products or had substantial loss of blood (more than 500 mL)
within 3 months before the first administration of study drug, or intention to donate
blood or blood products during the study.
12. Participated in an interventional study involving an experimental therapeutic agent
within 3 months of screening or prior to randomisation.
13. Women who have a positive serum ß-human chorionic gonadotropin (hCG) pregnancy test at
screening or a positive urinary hCG pregnancy test prior to randomisation, is
pregnant, lactating, or planning to become pregnant during the study.
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or
HIV results. Patients who are HBs antibody positive or HB core antibody positive are
not excluded provided the HBsAg result is negative. Patients who are HCV Ab positive
are not excluded if a subsequent HCV RNA test is negative.
15. Planned surgery or procedures during the participation of the study and for 28 days
after the conclusion of study participation.
16. Employee of the investigator or study centre with direct involvement in the proposed
study or other studies under the direction of that investigator or study centre, as
well as family members of the employees or the investigator.
17. Current or chronic history of liver disease or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
18. The patient is unable or unwilling to comply fully with the study protocol.
19. Patient is mentally or legally incapacitated.
20. Unable or unwilling to undergo multiple venepuncture procedures or the patient has
poor access to veins suitable for cannulation.
21. Any other reason that, in the opinion of the investigator, would make participation in
the study inadvisable.
22. A history of life-threatening COPD including Intensive Care Unit admission and/or
requiring intubation within the last 5 years.
23. A history of > 1 hospitalisation for COPD in the previous 1 year prior to screening.
24. Evidence of cor pulmonale or clinically significant pulmonary hypertension.
25. Requires routine treatment for COPD using one (or more) of the following therapies
within the 6 weeks before screening or prior to randomisation: Oral Beta-2 agonists
Methyl xanthines Phosphodiesterase (PDE) inhibitors Oral leukotriene inhibitors Oral
or parenteral glucocorticoids Antibiotic therapies for acute infections (Note: chronic
antibiotic use for prophylaxis, e.g. macrolides, is acceptable).
26. Other respiratory disorders: Patients with a current diagnosis of asthma, active
tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial
lung diseases, known alpha-1 antitrypsin deficiency or other active pulmonary diseases
other than COPD.
27. Patients with a history of chronic uncontrolled disease including, but not limited to,
cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal,
hematologic, urologic, immunologic, or ophthalmic diseases that, in the opinion of the
investigator, would make participation in the study inadvisable.
28. Patients with a history of sleep apnoea requiring non-invasive ventilation or
supplemental oxygen during sleep.
29. Previous lung resection or lung reduction surgery.
30. Active participation in a pulmonary rehabilitation program.
31. Has had major surgery within 6 weeks prior to screening or prior to randomisation.
32. A disclosed history, or one known to the Investigator, of significant noncompliance in
previous investigational studies or with prescribed medications.
33. History of unstable or uncontrolled hypertension or has been diagnosed with
hypertension in last 3 months prior to screening or prior to randomisation.
34. Requires supplemental oxygen, even on an occasional basis.
35. Received a live vaccine within 6 weeks prior to screening or prior to randomisation.
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