Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study to Evaluate the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate (FF/VI) Inhalation Powder Delivered Once Daily for 12 Weeks in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry Currently Treated With Low to Mid-strength Inhaled Corticosteroid or Low-strength Combination Therapy.
Brief Summary: A randomised, double-blind, placebo-controlled, parallel group multicentre study to evaluate the efficacy and safety of fluticasone furoate/vilanterol trifenatate (FF/VI) inhalation powder delivered once daily for 12 weeks in the treatment of asthma in adolescent and adult subjects of Asian ancestry currently treated with lowe to mid-strength inhaled corticosteroid or low-strength combination therapy.


Options:
A: Inclusion Criteria:

1. Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study
2. Type of Subject: Outpatients, of Asian ancestry, 12 years of age or older at Visit 1 (or ≥18 years of age or older if local regulations or the regulatory status of study medication permit enrolment of adults only) with a diagnosis of asthma as defined by the Global Initiative for Asthma \[GINA, 2009\] at least 12 weeks prior to Visit 1.
3. Gender: Male or Eligible Female, defined as non-childbearing potential or childbearing potential using an acceptable method of birth control consistently and correctly
4. Severity of Disease: A best FEV1 of 40%-90% of the predicted normal value at the Visit 1 Screening visit. Predicted values will be based upon NHANES III using the Asian adjustment
5. Reversibility of Disease: Demonstrated ≥12% and ≥200mL reversibility of FEV1 within 10-40minutes following 2-4 inhalations of albuterol/salbutamol inhalation aerosol (or one nebulized treatment with albuterol/salbutamol solution) at the Screening Visit.
6. Current Anti-Asthma Therapy: All subjects must be using an ICS, with or without LABA, for at least 12 weeks prior to Visit 1.
7. Short-Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhaler at Visit 1 for use as needed for the duration of the study. Subjects must be able to withhold albuterol/salbutamol for at least 4 hours prior to study visits.

Exclusion Criteria:

1. History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 10 years.
2. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4. Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
5. Other Concurrent Diseases/Abnormalities: A subjects must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
6. Oropharyngeal Examination: A subject will not be eligible for the Run-in if he/she has clinical visual evidence of candidiasis at Visit 1.
7. Allergies:

   * Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the new powder inhaler
   * Milk Protein Allergy: History of severe milk protein allergy.
8. Concomitant Medications: Use of the protocol defined prohibited medications within the prohibited time intervals prior to Screening (Visit 1) or during the study.
9. Tobacco Use: Current smoker or a smoking history of 10 pack years (e.g., 20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, smokeless or pipe tobacco).
10. Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub Investigator, study coordinator, or employee of the participating Investigator.
11. Previous Participation: A subject may not have previously been randomized to treatment in another Phase III FF/VI combination product study
12. Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator ) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries
B: Inclusion Criteria:

1. Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
2. Type of Subject: Outpatients, of Asian ancestry, 12 years of age or older at Visit 1 (or ≥18 years of age or older if local regulations or the regulatory status of study medication permit enrolment of adults only), with a diagnosis of asthma as defined by the Global Initiative for Asthma \[GINA, 2009\] at least 12 weeks prior to Visit 1.
3. Gender: Male or Eligible Female, defined as non-childbearing potential or childbearing potential using a protocol defined acceptable method of birth control consistently and correctly. Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required for females of childbearing potential at the initial Screening Visit (Visit 1) and Visit 5 or Early Withdrawal
4. Severity of Disease: A best FEV1 of 40%-90% of the predicted normal value at the Visit 1, Screening visit. Predicted values will be based upon NHANES III using the adjustment for Asians \[Hankinson, 2010\].
5. Reversibility of Disease: Demonstrated ≥12% and ≥200mL reversibility of FEV1 within 10-40minutes following 2-4 inhalations of albuterol/salbutamol inhalation aerosol (or one nebulised treatment with albuterol/salbutamol solution) at the Screening Visit.
6. Current Anti-Asthma Therapy: All subjects must be using an ICS, with or without LABA, for at least 12 weeks prior to Visit 1, in accordance with the protocol defined acceptable dose ranges.
7. Short-Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhaler at Visit 1 for use as needed for the duration of the study. Subjects must be able to withhold albuterol/salbutamol for at least 4 hours prior to study visits

Exclusion Criteria:

1. History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 10 years.
2. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4. Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
5. Other Concurrent Diseases/Abnormalities: A subjects must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
6. Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of candidiasis at Visit 1.
7. Allergies: •Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the new powder inhaler (i.e., lactose or magnesium stearate). •Milk Protein Allergy: History of severe milk protein allergy.
8. Concomitant Medications: Use of the protocol defined prohibited medications prior to Screening (Visit 1) or during the study, in accordance with the protocol.
9. Tobacco Use: Current smoker or subjects with a smoking history of 10 pack years (e.g., 20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, smokeless or pipe tobacco).
10. Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, Sub Investigator, study coordinator, or employee of the participating Investigator.
11. Previous Participation: A subject may not have previously been Randomized to treatment in another Phase III fluticasone furoate/VI combination product study (i.e., HZA113714, HZA106827, HZA106829, HZA106837, HZA106839, HZA106851, HZA113091).
12. Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries.
C: Inclusion Criteria:

Subjects eligible for enrolment in the study must meet all of the following criteria:

1. Type of subject: Subjects with documented GP diagnosis of COPD, and currently receiving maintenance therapy
2. Informed consent: Subjects must be able to provide informed consent, have their consent signed and dated. Subjects must be able to complete the electronic subject questionnaires or allow a proxy to do so on their behalf.
3. Gender and Age: Male or female subjects aged ≥40 years of age at Visit 1 A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH \> 40MIU/ml and estradiol \<40pg/ml (\<140 pmol/L) is confirmatory. Or child bearing potential has a negative urine pregnancy test at Visit 2, and agrees to one of the highly effective and acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - Visit 2 to the end of the study).
4. Subjects with Exacerbation History
5. Current COPD Maintenance Therapy

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

1. Subjects with any life threatening condition (e.g. low probability (in the opinion of the GP/Investigator) of 12 month survival due to severity of COPD or co-morbid condition) at the point of entry into the study.
2. Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the GP/ Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
3. Subjects with unstable COPD, defined as the occurrence of the following in the 2 weeks prior to Visit 2:

   - Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.
4. Chronic user of oral corticosteroids: Subjects who, in the opinion of the GP/Investigator, are considered to be a chronic user of oral corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening)
5. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g., beta-agonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the GP/ Investigator, contraindicates the subject's participation will also be excluded.
6. Investigational Medications: A subject must not have used any investigational drug treatment within 30 days prior to Visit 2 or within five half-lives (t½) of the prior investigational study (whichever is the longer of the two).
7. Subjects who plan to move away from the geographical area where the study is being conducted during the study period and/or if subjects have not consented to their medical records being part of the electronic medical records database that is operational in the Salford area.
D: Inclusion Criteria:

* Japanese healthy male subjects aged between 20 and 64 years of age inclusive. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history, physical examination, laboratory studies, and other tests.
* Body weight ≥ 50kg and BMI within the range 18.5-25.0kg/m2 inclusive.
* Non-smokers (never smoked or not smoking for \>6 months with \<10 pack years history (Pack years = (cigarettes per day smoked/20) x number of years smoked))
* Clinical laboratory tests data obtained at screening meet the following:

AST(GOT), ALT(GPT), total-bilirubin: below the upper limit of the normal ranges

* Normal 12-lead EGC finding at screening; QTc(B) interval \<450msec
* Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
* Rapid ACTH with normal range at the screening.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Capable of using the novel dry powder inhaler.

Exclusion Criteria:

* The subject has any clinically relevant abnormality on medical examination, vital sign, clinical laboratory test or medical history at screening in the medical opinion of the investigator or the subject has a medical history that is not considered as eligible for inclusion in this study by the investigator.
* The subject has an allergy for any drug or idiosyncrasy
* The subject has an allergy for any drug hypersensitivity to milk protein or the excipients lactose monohydrate and magnesium stearate.
* T he subject is currently participating in another clinical study or post-marketing study in which the subject is or will be exposed to an investigational or a non-investigational drug or device.
* The subject has participated in a clinical study with an investigational or a non-investigational drug or device during the previous 4 months.
* The subject has a history or current conditions of drug abuse or alcoholism.
* History of regular alcohol consumption exceeding on average, 14 drinks/week (1 drink = 5 ounces (150mL) of wine or 350mL of beer or 1.5 ounces (45mL) of 80 proof distilled spirits) within 6 month of screening.
* The subject is positive for urine drug at screening.
* Use of prescription or non-prescription drugs, including CYP3A/PGP inhibitor, vitamins, herbal and dietary supplements (including St John'sWort) within 14 days prior to the first dose of study medication.
* The subject has a known allergy or hypersensitivity to corticosteroids.
* The subject has a known allergy or hypersensitivity to synthetic ACTH
* The subject has a history of asthma in childhood or respiratory disorder.
* The subject is a permanent (or occasional during the study) night-shift worker\*.

  \* Permanent night shift worker defines as the person who has been continuing life that gets up after 12:00 day time and eats supper after 0:00 midnight for seven days or more usually.
* The subject is positive for syphilis, HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody.
* The subject has donated a unit of blood "\>400mL" within the previous 4 months or "\>200mL" within the previous 1 month.

Answer: B