Comparing Two Respiratory Drugs in Combination and Separately From a Novel Inhaler Device in Healthy Japanese Subjects
Comparing Two Respiratory Drugs in Combination and Separately From a Novel Inhaler Device in Healthy Japanese Subjects
A combination of the corticosteroid GW685698X and the long-acting ß2-agonist GW642444M is
 being developed for once daily administration for the maintenance treatment of asthma and
 COPD. GW642444M and GW685698X will be simultaneously co-administered from a single device and
 compared with GW642444M and GW685698X administered separately in order to determine whether
 co-administration affects the safety, tolerability, pharmacodynamic and/or pharmacokinetics
 of either compound in healthy Japanese subjects.
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.