| Eligibility |
Inclusion Criteria:
Healthy volunteers
- Able and willing to give written informed consent.
- Healthy male and female subjects, aged 18-80 years for the initial part and 40-80
years for the main part, inclusive. Women will be considered for inclusion if they
are: Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing.
Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
including any female who is pre-menarchial or post-menopausal, with documented proof
of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has
been amenorrhoeic for more than 1 year prior to the screening visit). Of childbearing
potential and using a highly effective method of contraception during the entire study
(vasectomised partner, sexual abstinence - the lifestyle of the female should be such
that there is complete abstinence from intercourse from two weeks prior to the first
dose of study medication until at least 72 hours after treatment -, implants,
injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs) or
double-barrier methods, i.e. any double combination of IUD, condom with spermicidal
gel, diaphragm, sponge, and cervical cap).
- Normal lung function with Forced Expiratory Volume in 1 second (FEV1) predicted = 80%
and FEV1/Forced Vital Capacity (FVC) > 70%.
- Body mass index between 18 and 32 kg/m2
- Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.
- Able and willing to give written informed consent
COPD subjects
- Male and female subjects, aged 40-80 years, inclusive. Women will be considered for
inclusion if they are: Not pregnant, as confirmed by pregnancy test (see flow chart),
and not nursing. Of non-child bearing potential (i.e. physiologically incapable of
becoming pregnant, including any female who is pre-menarchial or post-menopausal, with
documented proof of hysterectomy or tubal ligation, or meets clinical criteria for
menopause and has been amenorrhoeic for more than 1 year prior to the screening
visit). Of childbearing potential and using a highly effective method of contraception
during the entire study (vasectomised partner, sexual abstinence - the lifestyle of
the female should be such that there is complete abstinence from intercourse from two
weeks prior to the first dose of study medication until at least 72 hours after
treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs or
double-barrier methods, i.e. any double combination of IUD, condom with spermicidal
gel, diaphragm, sponge, and cervical cap).
- Clinical diagnosis of COPD stage II and III
- History of chronic cough and sputum production
- FEV1/FVC <70% post-bronchodilator at visit 1
- FEV1 30-80% of the predicted normal value post-bronchodilator at visit 1
- FEV1 >1.5 L
- Absence of lung emphysema assessed by pulmonary function measurement at visit 1: Total
Lung Capacity (TLC) <120% of predicted normal, Residual Volume (RV) <120% of predicted
normal, Diffusing Capacity for Carbon Monoxide (DLCO) >80%
- Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.
- Body mass index between 18 and 32 kg/m2.
- Able and willing to give written informed consent.
Exclusion Criteria:
Healthy volunteers
- Past or present disease, which as judged by the investigator, may affect the outcome
of the study or put the subject at risk because of participation in the study. These
diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic
disease, renal disease, haematological disease, neurological disease, psychiatric
disease, endocrine disease, infectious disease, inflammatory disease or pulmonary
disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic
fibrosis)
- Regular intake of any prescribed or over the counter medication. Exceptions include
paracetamol for pain relief, oral contraceptive medication, hormonal replacement
therapy, dietary and vitamin supplements
- Clinically relevant history of allergy as judged by the investigator
- Intolerance against standard medication used during bronchoscopy, e.g. lidocaine,
midazolam.
- Infections of the lower respiratory tract within 6 weeks prior to screening
- Infections of the upper respiratory tract within 2 weeks prior to screening
- Any clinically relevant abnormal findings in physical examination, clinical chemistry,
haematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the
opinion of the investigator, may either put the subject at risk because of
participation in the study, or may influence the results of the study.
- HIV (Type I + Type II), hepatitis B or C, tuberculosis, or Sars-CoV-2 positive or not
performed at visit 1
- Positive drug screen for methadone, cannabis, opiates, cocaine metabolites,
amphetamines, barbiturates and benzodiazepines at visit 1
- History of drug or alcohol abuse
- Risk of non-compliance with study procedures
- Suspected inability to understand the protocol requirements, instructions and
study-related restrictions, the nature, scope, and possible consequences of the study
COPD subjects
- Past or present disease other than COPD, which as judged by the investigator, may
affect the outcome of the study or put the subject at risk because of participation in
the study. These diseases include, but are not limited to, cardiovascular disease,
malignancy, hepatic disease, renal disease, haematological disease, neurological
disease, psychiatric disease, endocrine disease, infectious disease, inflammatory
disease or pulmonary disease (including but not confined to asthma, tuberculosis,
bronchiectasis or cystic fibrosis).
- Regular intake of any prescribed or over the counter medication, which as judged by
the investigator, may affect the outcome of the study or put the subject at risk
because of participation in the study. Explicitly allowed is treatment with
short-acting beta-2-agonists (SABA)/long-acting beta-2-agonists (LABA)/long-acting
muscarinic-antagonists (LAMA), paracetamol for pain relief, oral contraceptive
medication, hormonal replacement therapy, dietary and vitamin supplements. Not allowed
are inhaled corticosteroids.
- Clinically relevant history of allergy as judged by the investigator.
- Intolerance against standard medication used during bronchoscopy, e.g. lidocaine,
midazolam.
- Infections of the lower respiratory tract within 6 weeks prior to screening.
- Infections of the upper respiratory tract within 2 weeks prior to screening
- Exacerbation of COPD (treatment with oral or parenteral antibiotics and/or oral or
parenteral glucocoterticosteroids (GCS) and/or hospitalization related to COPD) within
60 days of visit 1.
- Any clinically relevant abnormal findings in physical examination, clinical chemistry,
hematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the
opinion of the investigator, may either put the subject at risk because of
participation in the study, or may influence the results of the study.
- HIV (Type I + Type II), hepatitis B or C, tuberculosis, or Sars-CoV2 positive or not
performed at visit 1.
- Positive drug screen for methadone, cannabis, opiates, cocaine metabolites,
amphetamines, barbiturates and benzodiazepines at visit 1.
- History of drug or alcohol abuse.
- Risk of non-compliance with study procedures.
- Suspected inability to understand the protocol requirements, instructions and
study-related restrictions, the nature, scope, and possible consequences of the study.
|
