Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-national, Randomized, Double-blind, Placebo-controlled, 3-period Crossover Study With GSK 573719 as Monotherapy in Adult Subjects With Asthma
Brief Summary: This is a multi-national, randomized, double-blind, 3-period crossover, incomplete block design to evaluate 5 once-daily and 2 twice-daily doses of GSK573719 in combination with placebo. The study will explore the dose range of GSK573719 in asthmatic subjects who are currently using non-ICS controller medications. Subjects will participate in the study for up to a maximum of 14 weeks. At randomization subjects will be stratified by age to ensure adequate exposure to GSK573719 throughout the expected age range. The primary endpoint will be trough FEV1 obtained 24 hours after the last morning dose on Day 14 of each treatment sequence.

A sub-group of subjects at selected sites (approximately 30% of the total population) will have additional serial assessments for spirometry, ECG and Holter, and pharmacokinetic sampling at the start and end of each treatment period. Safety assessments will include monitoring for adverse events, laboratory tests, asthma symptom assessments and twice daily PEF evaluation. Consenting subjects will have a blood sample taken for pharmacogenetic analysis.


Options:
A: Inclusion Criteria:

* Male or female outpatients aged ≥ 18, who have signed an Informed Consent form prior to initiation of any study-related procedure.
* Clinical diagnosis of asthma for a minimum of 12 months prior to screening confirmed by a chest physician according to international guidelines (GINA). The evidence of asthma must be confirmed through a documented (in the last three years) positive response to the reversibility test, defined as ΔFEV1 ≥ 12% and ≥ 200 mL over baseline, within 30 minutes after administration of 400 μg of salbutamol pMDI or through a documented (in the last three years) positive response to methacholine challenge test (PC20 \< 8 mg/mL or PD20 \< 1 mg).
* Baseline FEV1 \> 80% of the predicted normal value after appropriate washout from bronchodilators (to be checked at screening and at randomisation visits).
* Asthma Control Test score ≥ 20 and \< 25 (to be checked at screening and at randomisation visits).
* Impaired small airways function defined as baseline peripheral airway resistance \[R(5Hz)-R(20Hz)\] ≥ 0.07 kPa/L/s (to be checked at screening and at randomisation visits).
* Patients on previous regular treatment with Seretide® Accuhaler® (fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation, daily dose of fluticasone 500 μg plus salmeterol 100 μg) at a stable dose for at least 2 months prior to inclusion.
* A cooperative attitude and ability to be trained to the proper use of DPI.

Main Exclusion Criteria:

* Patients with a diagnosis of COPD according to GOLD guidelines.
* Current smokers with a smoking history of \> 10 pack/year.
* Patients who have a clinical or functional uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might, in the judgment of the investigator, represent for the patients an undue risk or that could compromise the results or interpretation of the study.
* History or current evidence of uncontrolled heart failure, clinically relevant coronary artery disease, recent myocardial infarction, severe hypertension, uncontrolled cardiac arrhythmias.
* Patients treated with LABA or ICS/LABA fixed combination in the 24 hours before the screening visit.
* Severe asthma exacerbation leading to intake of systemic corticosteroids (\> 10 days) in the month before the screening visit.
B: Inclusion Criteria:

* Patients with a documented diagnosis of persistent asthma and who were currently treated with or qualified for treatment with both ICS and long-acting beta2-agonist (LABA) combination
* Patients demonstrating an increase in forced expiration volume in 1 second (FEV1) of ≥ 12% or ≥ 200 mLs within 30 minutes after administration of short-acting beta2-agonist (SABA)
* Patients with an FEV1 ≥ 50% of predicted normal

Exclusion Criteria:

* Patients with a previous diagnosis of chronic obstructive pulmonary disease (COPD)
* Patients who had an asthma attack/exacerbation requiring hospitalization/emergency room visit or respiratory tract infection within 1 month prior to randomization
* Patients who had ever required ventilator support for respiratory failure
* Patients with diabetes Type I or uncontrolled diabetes Type II
* Patients with concomitant pulmonary disease
* Patients with certain cardiovascular co-morbid conditions
* Patients with any significant medical condition that might compromise patient safety, interfere with evaluation or preclude completion of the study

Other protocol-defined inclusion/exclusion criteria may apply
C: Inclusion Criteria:

* Subjects must have their own Android or iPhone operating system (IOS) mobile device (example given \[e.g.\] smart phone or tablet) and a data package suitable for the installation and running of the app and sending and receiving data. Data used by the CIS is approximately 1 megabyte (MB) per month as a maximum; this is less data than a 1 minute video streamed from YouTube (2MB).
* Subjects must be willing and able to download the app on their personal mobile device and keep it turned on for the duration of the study. This will also require Bluetooth to be turned on for duration of the study. Subjects will also have to turn on mobile data for the app for the duration of study; unless travelling and when extra data roaming costs could be incurred.
* Subjects must be 18 years of age or older at the time of signing the informed consent.
* Subjects with a documented diagnosis of asthma by a respiratory physician or subjects with a documented asthma diagnosis by their general practitioner (GP) are required to have spirometry consistent with the diagnosis of asthma (e.g., reduced FEV1, reduced FEV1/forced vital capacity (FVC), or variable airflow obstruction) at or before Visit 0.
* Subjects who are able to perform spirometry that conforms to American Thoracic Society/ European Respiratory Society(ATS/ERS) technical standards at Visit 0 or Visit 1.
* Subjects are eligible if they require daily ICS/ long-acting beta-agonist (LABA) therapy (with a stable total daily dose of ICS of \>250 microgram per day \[mcg/day\] FP, or equivalent) for at least 4 weeks prior to screening. Dosing regimen (once or twice daily to equal the total daily dose) should be restricted to the current local product labels/treatment guidelines.
* Subjects with inadequately controlled asthma (ACT total score \<20) despite ICS/LABA maintenance therapy at Visit 1.
* Male or Female subjects will be included in the study. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 5 days after the last dose of study treatment. The Investigator is responsible for ensuring that subject understands how to properly use these methods of contraception.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases including chronic obstructive pulmonary disease (COPD) or abnormalities other than asthma.
* Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation (e.g. very low body mass index \[BMI\] or severely malnourished), or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
* Subjects with any of the following at screening would be excluded: myocardial infarction or unstable angina in the last 6 months; unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.
* Moderate or severe hepatic impairment in subjects receiving high dose ICS.
* Subjects with a history of allergy or hypersensitivity to any corticosteroid, anticholinergic/ muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate are excluded from participation in this study.
* Subjects with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.
* Subjects with active uncontrolled psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
* 30 days or within 5 drug half-lives of the investigational drug (whichever is longer).
* Subjects who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.
* Smokers will be excluded as follows: current smokers (defined as subjects who have used inhaled tobacco products within the 12 months prior to screening \[that is {i.e.}, cigarettes, e-cigarettes/vaping, cigars or pipe tobacco\]); former smokers with a smoking history of \>=10 pack years (e.g., \>=20 cigarettes/day for 10 years).
* Subjects unable to comply with the study procedures due to infirmity, disability, or geographic location.
* Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.
* In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials.
* Subjects who have taken part in more than 1 clinical trial in the 12 months prior to Visit 1 and/or subjects who have taken part in any of the following clinical trials in the 12 months prior to Visit 1: a clinical trial including audio and/or visual reminders for the subject to take their study treatment; any clinical trial during the 4 weeks prior to Visit 1;GSK study 207040.
D: Inclusion Criteria:

* Written informed consent
* Outpatient (sub-group will have 3 overnight stays at clinic)
* Diagnosis of asthma (NIH 2007) for at least 6 months
* Male or Eligible female (females of child-bearing potential must use acceptable method of birth control)
* A best AM pre-bronchodilator FEV1 of 60% to 85% of predicted normal value at Screening
* Reversibility of disease demonstrated by at least 12% and 200mL increase in FEV1 .
* Subjects must have been prescribed a non-corticosteroid controller at least 3 months preceding Visit 1, and/or a short-acting beta 2 agonist, without the use of inhaled corticosteroids in the 4 weeks prior to Visit 1
* Subjects must be able to replace their current short-acting Beta-2-agonist with albuterol/salbutamol aerosol inhaler for the duration of the study
* Subjects must be judged capable of withholding albuterol/salbutamol for at least 4 hours prior to study visits

Exclusion Criteria:

* History of life threatening asthma
* Severe asthma exacerbation
* Respiratory infection within expected to affect subject's ability to participate
* Concurrent respiratory disease
* Current smoker or smoking history of 10 pack years or more
* Diseases preventing use of anticholinergics
* Other clinically significant, uncontrolled condition or disease which would pose a safety risk to the patient, or confound interpretation of study results
* Drug allergy to any Beta-2-agonist, sympathomimetic drug, intranasal, inhaled or systemic corticosteroid therapy
* Known or suspected sensitivity to the constituents of the Novel DPI (ie lactose)
* History of severe milk protein allergy
* Administration of prescription or over-the-counter medication that would significantly affect the course of asthma, or interact with the study drug
* Any infirmity, disability or disease of a child or family member likely to impair compliance
* Alcohol or substance abuse history
* Viral hepatitis B surface antigen or Hepatitis C antibody
* Known HIV-positive history.
* Affiliation with investigator or site staff

Answer: D