Two-part Pharmacokinetic and Pharmacodynamic Study of LAS190792 in Patients With Asthma and COPD

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 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 mo