Two-part Pharmacokinetic and Pharmacodynamic Study of LAS190792 in Patients With Asthma and COPD
Condition: Chronic Obstructive Pulmonary Disease (COPD); Asthma
MeSH terms: Asthma; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: LAS190792 Dose 1; LAS190792 Dose 2; LAS190792 Dose 3; LAS190792 Dose 4; LAS190792 Dose 5; LAS190792 Dose 6; LAS190792 Dose 1 (Part 2); LAS190792 Dose 2 (Part 2); Tiotropium 18 μg; Indacaterol 150 μg; Placebo
Intervention MeSH terms: Tiotropium Bromide; LAS190792
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety and tolerability of single doses of
      LAS190792 administered by inhalation to patients with mild persistent asthma and moderate to
      severe chronic obstructive pulmonary disease (COPD) and also to assess the ability of
      LAS190792 to produce bronchodilation (opening of the airways).
    

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