Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Single-dose, Dose-ascending, Double Blind, Placebo-controlled, 5-way Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Doses of GW642444M With Magnesium Stearate in Asthmatic Patients
Brief Summary: This study will involve the use of a new compound, GW642444 that is being developed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. When a medicine is made into a form ready to be given to patients, the active ingredient is often prepared with another ingredient called a salt to help make it stable, and inactive ingredients are often added. Inactive ingredients might be used to help a medicine work better, to make it easier to produce the medicine, or to make it easier to get an accurate dose of medicine. In previous studies the study drug has been given as a dry powder containing either the "H" salt (with the inactive ingredient lactose), or containing the "M" salt (with the inactive ingredients lactose and cellobiose octaacetate). The "M" salt form of the study drug has been altered to contain lactose and a new inactive ingredient called magnesium stearate (instead of cellobiose octaacetate).

Participants in this study will receive both the "H" salt (GW642444H) and the new "M" salt (GW642444M) containing magnesium stearate. This study will be the first time the new "M" salt form of the study drug will be given to asthmatic patients.


Options:
A: 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.
B: Inclusion criteria:

* male or female (of non-childbearing potential) between 18 - 70 years
* History of stable mild to moderate asthma
* non - smokers
* currently taking daily doses of inhaled fluticasone propionate 200 - 500 mcg (or equivalent)
* body weight \>50 kg with BMI 19-29.9 kg/m2
* normal ECG assessment

Exclusion criteria:

* history of significant disease
* history of life threatening asthma
* recent respiratory tract infection
* recent change of asthma medication
* treatment with high dose inhaled corticosteroids or oral corticosteroids
* recent participation in another trial
* history of drug or alcohol abuse
* known allergies (excluding asthma)
* recent blood donation
C: Inclusion Criteria:

1. 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.
2. Body weight ≥ 50kg and BMI within the range 18.5-25.0kg/m2 inclusive.
3. 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))
4. Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
5. Clinical laboratory tests data obtained at screening meet the following:

   AST(GOT), ALT(GPT), total-bilirubin: below the upper limit of the normal ranges
6. Serum potassium and glucose within normal range at screening
7. Normal 12-lead EGC finding at screening; QTc interval \<450msec
8. A mean heart rate within the range 40-90 beats per minute (bpm) inclusive at screening.
9. A mean blood pressure lower than 140/90mmHg at screening.
10. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
11. Capable of using the novel dry powder inhaler.

Exclusion Criteria:

1. 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.
2. The 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.
3. The subject has participated in a clinical study with an investigational or a non-investigational drug or device during the previous 4 months.
4. A history of breathing problems (i.e. history of asthmatic symptomatology, asthma in childhood).
5. The subject has an allergy for any drug or idiosyncrasy
6. The subject has a known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and magnesium stearate.
7. The subject has a history or current conditions of drug abuse or alcoholism.
8. 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.
9. The subject is positive for urine drug screening.
10. 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.
11. The subject is positive for syphilis, HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody.
12. The subject has donated a unit of blood "\>400mL" within the previous 4 months or "\>200mL" within the previous 1 month.
D: Inclusion Criteria:

* At least 6 and maximally 15 years of age
* Diagnosis of asthma and baseline lung function tests as determined by the protocol
* Has required and received treatment with inhaled corticosteroids within the timeframe and doses specified in the protocol

Exclusion Criteria:

* Severe asthma
* Has required treatment with any non-inhaled corticosteroids within previous 4 weeks, has sensitivity to drugs specified in the protocol or requires treatment with beta-blockers

Answer: B