Study of Danirixin in Japanese Healthy Elderly Male Subjects
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: GSK1325756H; Placebo
Intervention description: Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.; Subjects will receive visually matching danirixin placebo tablets. It will be administered with 240 mL of water.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 34.0
Sex: Male
Minimum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy Japanese subjects; CXCR2 inhibitor; Danirixin

Summary:

      Danirixin is a selective chemokine receptor antagonist being developed as a potential
      anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD).
      The aim of the study is to assess the safety, tolerability and pharmacokinetics (PK) in
      healthy Japanese subjects over the age of 65 years (inclusive). The study will be conducted
      in two parts: Part 1 will be a double blind, placebo-controlled, 3-period crossover,
      ascending single oral dose administration of GSK1325756H (Hydrobromide Salt Tablet
      Formulations of Danirixin) 10, 50 and 100 milligram (mg) in the fed condition. Part 2 will be
      an open label, 2-period crossover, single oral dose of GSK1325756H 50 mg in fed and fasted
      state. This study will provide an understanding of PK of hydrobromide salt of GSK1325756 in
      population of healthy elderly subjects and also contribute to the selection of appropriate
      dosing for Phase IIa study in Japan.
    

Eligibility criteria:

        Inclusion Criteria

          -  Participant must be over 65 years of age inclusive, at the time of signing the
             informed consent.

          -  Participants who are overtly healthy as determined by medical evaluation including
             medical history, physical examination, laboratory tests, and ECG. A subject with a
             clinical abnormality or laboratory parameter(s) which is/are not specifically listed
             in the inclusion or exclusion criteria, outside the reference range for the population
             being studied may be included only if the investigator in consultation with the
             Medical Monitor if required agree that the finding is unlikely to introduce additional
             risk factors and will not interfere with the study procedures.

          -  Participants whose peripheral blood neutrophil counts and hematocrit values are within
             normal range at screening visit.

          -  Body weight >=50 kilogram (Kg) and body mass index (BMI) within the range 18.5-24.9
             kg/square meter (m^2) (inclusive).

          -  Japanese Male: A male participant must agree to use contraception during the treatment
             period and until follow up visit.

          -  Capable of giving signed informed consent.

        Exclusion Criteria

          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
             endocrine, hematological, or neurological disorders capable of significantly altering
             the absorption, metabolism, or elimination of drugs; constituting a risk when taking
             the study treatment; or interfering with the interpretation of data.

          -  Abnormal blood pressure as determined by the investigator.

          -  Alanine Aminotransferase (ALT)>1.5x upper limit of normal (ULN).

          -  Bilirubin>1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin < 35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QT interval corrected for heart rate according to Fridericia's formula (QTcF)> 450
             millisecond (msec).

          -  Past or intended use of over-the-counter or prescription medication including herbal
             medications and proton pump inhibitor (PPI) within 14 days prior to dosing.

          -  History of donation of blood or blood products >=400 milliliter (mL) within 3 months
             or >=200 mL within 1 month prior to screening.

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  Current enrolment or past participation within the last 30 days before signing of
             consent in this clinical study involving an investigational study treatment or any
             other type of medical research.

          -  The subject with positive Serological test for syphilis (Rapid Plasma Reagin [RPR] and
             Treponema pallidum hemagglutination test [TPHA]), Human immunodeficiency virus (HIV)
             Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV)
             antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.

          -  Positive pre-study drug screen.

          -  Regular alcohol consumption within 6 months prior to the study defined as: an average
             weekly intake of > 14 units for males. One unit is equivalent to 350 mL of beer, 150
             mL of wine or 45 mL of 80 proof distilled spirits.

          -  Smoking or history or regular use of tobacco- or nicotine-containing products within 6
             months prior to screening.

          -  Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy that, in the opinion of the investigator or medical monitor, contraindicates
             participation in the study.