Intervention: Tiotropium
Trial phase: Phase 1
ATC code: R03AL06 | R03AL10 | R03BB04 | R03BB54
SMILES: [H][C@]1(OC(=O)C(O)(c2cccs2)c2cccs2)C[C@@]2([H])[C@]3([H])O[C@]3([H])[C@@]([H])(C1)[N+]2(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 37
Group description: Single dose, oral inhalation by HandiHaler® single-dose dry powder inhaler (DPI)
Eligibility criteria:
Inclusion Criteria (PART 1):

Adult male subjects aged 18 to 70 years
Body mass index (BMI) 18.5 to 30 kg/m2 at screening
Clinical diagnosis of mild persistent asthma (according to GINA guidelines) for at least 6 months prior to screening
Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods
Screening FEV1 value of ≥70% of the predicted normal value after a washout of at least 5 h for short-acting beta2-agonists and 72 h for long-acting beta2-agonists
FEV1 reversibility of ≥12% and an absolute increase of at least 200 mL over the baseline value within 30 min after inhalation of 400 µg of salbutamol
Subjects using intermittent salbutamol and / or subjects on a stable dose or regimen of low dose ICS (as defined by the GINA guidelines) at least 4 weeks prior to screening
Predose FEV1 value of first treatment period within the range of ±20% of the FEV1 measured at screening prior to salbutamol inhalation
Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings
Normal blood pressure (defined as SBP between 100 and 140 mmHg, and DBP between 50 and 90 mmHg) at screening, measured after resting in supine position for 5 minutes.
Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator
Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody (IgM), hepatitis C antibody and human immunodeficiency virus (HIV) I and II antibodies at screening
Subjects who are able and willing to provide written informed consent
Subjects able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005 criteria at screening

Inclusion Criteria (PART 2):

Adult male and non-childbearing potential women subjects aged ≥40 years with a clinical diagnosis of stable moderate to severe COPD according to GOLD guidelines at screening
Females must be of non-childbearing potential, confirmed at screening
Post-salbutamol FEV1 <80% and ≥30% of the predicted normal value and post-salbutamol FEV1 / forced vital capacity (FVC) <70%
Ability to change current COPD therapy, to discontinue previous prescribed medications after signature of informed consent
No evidence of clinically significant respiratory and / or cardiovascular conditions or laboratory abnormalities
No other relevant pulmonary disease or history of thoracic surgery
No contraindication to the use of anticholinergic drugs such as known symptomatic prostatic hypertrophy, bladder neck obstruction, narrow-angle glaucoma, or beta2-agonists usage
Subjects who are negative for HBsAg, HBc IgM, hepatitis C antibody and HIV I and II antibodies at screening
Subjects who are able and willing to provide written informed consent
Subjects able to perform repeatable pulmonary function testing for FEV1 according to the ATS / ERS 2005 criteria at screening

Exclusion Criteria (PART 1 and 2):

Subjects who do not conform to the above inclusion criteria
Current smokers, subjects with a smoking history during the last 12 months or subjects with a smoking history of more than 10 pack-years
Other relevant pulmonary disease or history of thoracic surgery
Subjects with a BMI ≥40 kg/m2 (only applicable for Part 2)
Subjects with any clinically relevant history or presence of abnormality from the medical history and/or physical examination (only applicable for Part 1)
Current evidence or recent history of any clinically significant and unstable disease (other than COPD) or abnormality that could put the subject at risk or could confound the results of the study (only applicable for Part 2)
Subjects with a surgical history clinically relevant for the purpose of the study
History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin
Subjects with serious adverse reaction or serious hypersensitivity to Spiriva (for Part 2 only), indacaterol (for Part 2 only), or the formulation excipients (eg, lactose) or other drugs in the same pharmacologic class (for Part 1 and Part 2)
Current diagnosis of COPD (for Part 1 only) or history of / or current diagnosis for asthma (for Part 2 only)
Recent history of asthma / COPD exacerbation requiring hospitalisation or need for increased maintenance treatments for asthma / COPD within 6 weeks prior to screening or randomisation
Use of daily oxygen therapy >10 h per day (for Part 2 only)
Use of systemic steroids for respiratory reasons within 3 months prior to screening
Lower respiratory tract infection within 6 weeks prior to screening or randomisation
Upper respiratory tract infection requiring antibiotics within 4 weeks prior to screening or randomisation
Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease
QTcF interval >430 ms at screening or prior to randomisation, or history of long QT syndrome (for Part 1 only)
QTcF interval, >450 ms for males and >470 ms for females at screening or prior to randomisation, or history of long QT syndrome (for Part 2 only)
Subjects with a history of excessive use or abuse of alcohol or with a history of drug abuse within the past 2 years
Subjects who are positive for drugs of abuse and alcohol tests at screening and prior to randomisation
Donation or loss >400 ml of blood and plasma within the previous 3 months prior to screening
Subjects consuming more than 14 (female subjects) or 21 (male subjects) units of alcohol a week
Subjects with a significant infection or known inflammatory process at screening or prior to randomisation
Subjects with acute gastrointestinal symptoms at the time of screening or prior to randomisation
Subjects with an acute infection such as influenza at the time of screening or prior to randomisation
Male subjects who do not agree to follow instructions to avoid pregnancies
Subjects who are not able to adhere to the restrictions on prior and concomitant medications
Subjects who intend to use any concomitant medication not permitted by the protocol or who have not undergone the required washout period for a particular prohibited medication
Subjects who have used any investigational drug within 3 months prior to screening or within the equivalent time of 6 half-lives of receiving the last administration, whichever is longer
Subjects who have received the last dose of investigational product more than 3 months ago but who are on an extended follow-up
Subjects who are vegans or who have medical dietary restrictions
Subjects unable to communicate reliably with the Investigator
Subjects who are unlikely to co-operate with the requirements of the study