Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I Study of GW685698X-A Randomized, Double Blind, Placebo Controlled, Parallel-group, Repeat Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Dose From a Novel Dry Powder Device in Healthy Japanese Male Subjects.
Brief Summary: This is a randomized, double blind, placebo controlled, parallel-group, repeat dose study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled dose from a novel dry powder device in healthy Japanese male subjects.


Options:
A: 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.
B: Inclusion criteria:

* Healthy male adults aged between 20 and 60 years inclusive
* Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.
* Male subjects must use double-barrier (condom/spermicide) birth control methods or abstain from sexual intercourse with female partners who are pregnant, lactating, or able to bear children in addition to any birth control method the female partner is using, from the first dose of study medication until 90 days after the last dose of study medication.
* Japanese ethnic origin (defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese)
* Body weight ≥ 45 kg and body mass index within the range of 18-28 kg/m2 inclusive.
* No significant abnormality on 12-lead ECG at screening, including the following specific requirements:

  * Ventricular rate ≥ 45 beats per minute
  * PR interval ≤ 210msec
  * Q waves \< 30msec (up to 50 ms permitted in lead III only)
  * QRS interval to be ≥ 60msec and ≤ 120msec
  * The waveforms must enable the QT interval to be clearly defined
  * QTc interval must be \< 450msec (QTcB or QTcF; machine or manual reading) based on a single ECG value, or an average from three ECGs obtained over a brief recording period
* No significant abnormality on the Holter ECG at screening.
* FEV1 ≥90% predicted and FEV1 / FVC ratio ≥ 0.7 at screening
* Subjects who are current non- smokers who have not used any tobacco products in the 12 month period preceding the screening visit and have a pack history of \< 5 pack years
* Signed and dated informed consent is obtained for the subject
* Subjects who are able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
* Subjects who are able to use the inhalation device satisfactorily

Exclusion Criteria:

* As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
* The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
* Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
* Liver function tests (AST, ALT or ALP) greater than 1.5 of the upper limit of laboratory reference range.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
* History of milk protein allergy.
* The subject has taken prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
* The subject has taken oral corticosteroids less than 8 weeks before the screening visit
* The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit
* History of alcohol/drug abuse or dependence within 12 months of the study
* Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a 285mL glass of full strength beer or 425mL schooner of light beer or 1 (30mL) measure of spirits or 1 glass (100mL) of wine
* The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* The subject has donated a unit (450mL) of blood within the previous 16 weeks or intends to donate within 16 weeks after completing the study.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* The subject has tested positive for HIV antibodies.
* The subject has a positive pre-study urine drug screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
* Positive CO or alcohol breath test at screening or on admission to the Unit.
* History of any adverse reaction including immediate or delayed hypersensitivity to any ICS, β2 agonist or sympathomimetic drug.
* Any known or suspected sensitivity to the constituents of GW642444M or GW685698X inhalation powder (i.e., lactose, magnesium stearate).
* Subjects at risk of non-compliance.
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:

* 18 years of age or older
* COPD with evidence of an asthmatic component as demonstrated by spirometry, reversibility and current therapy at screening as follows:

  * Post-bronchodilator morning (AM) FEV1 \>=50% and \<=80% of the predicted normal value at Visit 1
  * Pre- and post-bronchodilator FEV1/FVC ratio \<0.7.
  * Demonstrated reversibility by \>=12% and \>=200 mL increase in FEV1 following albuterol at Visit 1.
  * A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long-acting beta-agonist or leukotriene modifier, etc.) for a minimum of 12 weeks prior to Visit 1.
* Outpatient subjects who are smokers or non-smokers.

Exclusion Criteria:

* History of life-threatening respiratory event within the last 5 years.
* Unresolved respiratory infection
* Recent Severe COPD or Asthma Exacerbation
* Risk factors for pneumonia
* Hospitalization for pneumonia within 3 months
* Concurrent respiratory disease other than chronic obstructive pulmonary disease or asthma.
* Other uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
* Viral hepatitis or HIV
* Current or chronic history of liver disease, known hepatic or biliary abnormalities
* Drug or milk protein allergy
* Administration of prescription or over-the-counter medication that would significantly affect the course of COPD or asthma, or interact with study drug
* Subjects with lung volume reduction surgery within 12 months prior to screening.
* Use of long-term oxygen therapy (LTOT)
* Requirement for nebulized therapy
* Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks
* Unstable or life-threatening cardiac disease
* Abnormal and clinically significant 12-Lead Electrocardiogram (ECG) finding
* Diseases preventing the use of anticholinergics

Answer: A