Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Partially-Blinded, Randomized, 24-Week, Parallel-Group, Non-Inferiority, Open-Label Active Controlled Study to Compare the Efficacy and Safety of QVM149 With a Free Triple Combination of Salmeterol/Fluticasone + Tiotropium in Patients With Uncontrolled Asthma
Brief Summary: The purpose of this trial was to demonstrate that the efficacy of two treatment arms of the fixed-dose combination product QVM149 was non-inferior to the efficacy of the free combination arm of salmeterol/ fluticasone+ tiotropium in uncontrolled moderate to severe asthmatic patients.

The planned duration of treatment in this study was 24 weeks, followed up by a 7-day follow-up period.


Options:
A: Inclusion Criteria:

* Outpatients aged between 16- 65 years.
* Male and female; female subjects must be non-child bearing potential or of childbearing potenetial with negative pregnancy test and willing to use acceptable contraceptive methods
* Documented clinical history of persistent asthma first diagnosed at least 6 months prior to Visit 1
* Currently receiving inhaled short-acting beta-2 agonists for symptom relief
* A lung function of between 50 to 90% predicted (PEF)
* Increase in PEF of at least15%, 20 minutes after inhalation of 400mcg salbutamol

Exclusion Criteria:

* History of respiratory tract infection and/or exacerbation of asthma within a period of 4 weeks prior to Visit 1
* History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxia seizures.
* A history of two or more asthma exacerbations requiring treatment with oral corticosteroids or hospitalisation in the 6 months before Visit 1.
* Past or present disease that, as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematologic disease, neurological disease, endocrine disease or pulmonary disease (including, but not confined to, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis and bronchopulmonary dysplasia).
* Known or suspected sensitivity to corticosteroids, VENTOLIN, or the constituents of ROTADISKS (e.g., lactose).
* Undergoing allergen desensitisation therapy.
* Neurological or psychiatric disease or history of drug or alcohol abuse that would interfere with the subject's proper completion of the protocol requirements.
* Is a current smoker or has a smoking history of 10 pack years or more (e.g., 20 cigarettes/day for 10 years). Note: Current smoker is defined as currently smoking or stopped smoking within 6 months of screening visit.
B: Inclusion Criteria:

* Ability to confirm voluntary participation and agree to all trial purposes by signing and dating the informed consent forms;
* Participants aged 18 years or more;
* Diagnosis of uncontrolled severe asthma;
* Participants with Forced expiratory volume in 1 second (FEV1) \> 60% of predicted;

Exclusion Criteria:

* Any clinical and laboratory findings that, in the judgment of the investigator, may interfere with the safety of research participants;
* Known hypersensitivity to the formula components used during the clinical trial;
* History of alcohol and/or substance abuse within 12 months prior to Screening Visit.
* Current smoking or smoking history equivalent to "10 pack years"
* Participants with untreated oral candidiasis;
* Pulmonary disease history (e.g., chronic obstructive pulmonary disease \[COPD\], cystic fibrosis, bronchiectasis, tuberculosis);
* Participants with a history of acute asthma exacerbation, respiratory tract infection or hospitalization for asthma in the last 4 weeks;
* Known HIV-positive status or active hepatitis B or C virus test result
* Participants with current evidence or history of uncontrolled coronary artery disease, congestive heart failure, myocardial infarction or cardiac arrhythmia;
* Participants with a current medical history of cancer and/or cancer treatment in the last 5 years;
* Participants using medications that would have an effect on bronchospasm and / or lung function.
C: Inclusion Criteria:

* Signed informed consent
* Outpatient at least 12 years of age with diagnosis of asthma at least 12 weeks prior to first visit
* Both genders; females of child bearing potential must be willing to use appropriate contraception
* Pre-bronchodilator FEV1 of 40-90% predicted
* Reversibility FEV1 of at least 12% and 200mLs
* Current asthma therapy that includes inhaled corticosteroid for at least 4 weeks prior to first visit

Exclusion Criteria:

* History of life threatening asthma
* Respiratory infection or candidiasis
* Asthma exacerbation requiring OCS within last 4 weeks or overnight hospital stay within the last 3 months
* Concurrent respiratory disease or other disease that would confound study participation of affect subject safety
* Allergies to study drugs, study drug excipients, medications related to study drugs
* Taking another investigational medication or medication prohibited for use during the study
* Previous treatment with FF or FF/VI in a phase II or III study
* Night shift workers
* Children in care
D: Inclusion Criteria:

* Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1 with current asthma severity ≥ step 4 (GINA 2017).
* Patients who had used ICS/LABA combinations for asthma for at least 3 months and at stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1.
* Patients were required to be symptomatic at screening despite treatment with medium or high stable doses of ICS/LABA as defined by ACQ-7 score ≥ 1.5 at visits 101 and 201 (randomization visit).
* Patients with history of at least one severe asthma exacerbation which required medical care from a physician, emergency room visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid treatment for at least 3 days including physician guided self-management treatment with oral corticosteroids as part of written asthma action plan.
* Pre-bronchodilator FEV1 of \< 85 % of the predicted normal value for the patient after withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201.
* Patients who demonstrated an increase in FEV1 of ≥ 12% and 200 ml.

Exclusion Criteria:

* Patients who had a smoking history of greater than 20 pack years.
* Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
* Patients who had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening).
* Patients treated with a LAMA for asthma within 3 months prior to Visit 1.
* Patients who had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 201.

Answer: D