GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: Danirixin; Omeprazole
Intervention description: Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.; Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.
Intervention MeSH terms: Omeprazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects will receive danirixin reference and test formulations in a cross-over manner.
Masking: None (Open Label)
Masking description: This will be an open-label study and blinding will not be performed.
Enrollment: 40.0
Sex: All
Minimum age: 65 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Danirixin; Healthy; Food effect; Relative Bioavailability; Hydrobromide Salt

Summary:

      This 2-part study will be carried out on healthy elderly subjects to evaluate relative
      bioavailability of danirixin formulations. Part A will support the selection of the
      formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK)
      profile of selected formulation from Part A. Danirixin is currently administered with food,
      therefore the investigation of food effect for the selected formulation could potentially
      enable dosing without food. Approximately 16 subjects will be included in Part A and
      approximately 24 subjects will be included in Part B. Both parts will include a screening
      phase, treatment phase with in-between washout period and a follow-up phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.

          -  Subjects who are healthy, as determined by a responsible and experienced physician,
             based on a medical evaluation including medical history, physical examination,
             laboratory tests and cardiac monitoring or a subject with a clinical abnormality or
             laboratory parameters outside the reference range for the population being studied may
             be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree
             that the finding is unlikely to introduce risk factors and will not interfere with the
             study procedures and objectives. Additionally, laboratory assessments that are
             specifically listed in the inclusion or exclusion criteria and are outside of the
             reference range can be repeated once during the screening period.

          -  Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg
             per meter square (kg/m^2) (inclusive).

          -  Male or female subjects will be included. A female subject is eligible to participate
             if she is not pregnant, not breastfeeding, and at least one of the following
             conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who
             agrees to follow the contraceptive guidance during the treatment period and for at
             least 60 hours after the last dose of study treatment.

          -  Capable of giving signed informed consent.

          -  AST, ALT, alkaline phosphatase and bilirubin <= 1.5 × upper limit of normal (ULN)
             (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct
             bilirubin < 35 percent).

          -  Resting BP of <= 160/90 millimeters of mercury (mmHg), irrespective of
             anti-hypertensive medication status for the subject.

          -  Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30
             minutes in each of the four treatment periods where study treatment is administered in
             a fed state.

        Exclusion Criteria:

          -  Significant history of or current 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.

          -  Evidence of active or latent tuberculosis (TB) as documented by medical history and
             examination, chest x-rays (posterior anterior and lateral), and TB testing: either a
             positive tuberculin skin test [TST; defined as a skin induration <5 millimeter (mm) at
             48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination
             history] or a positive (not indeterminate) QuantiFERON®-TB Gold test.

          -  Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or
             squamous epithelial carcinomas of the skin that have been resected with no evidence of
             metastatic disease for 3 years.

          -  Breast cancer within the past 10 years.

          -  ALT >1.5x ULN

          -  Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35 percent).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Corrected QT interval (QTc) >450 milliseconds (msec).

          -  Use of prescription or non-prescription drugs, including proton pump inhibitors,
             histamine receptor 2 antagonists, systemic antacid medications (unless these can be
             held during the study), 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 longer) prior to the first dose of study treatment until
             completion of the last study assessment , unless in the opinion of the investigator
             and GSK Medical Monitor, the medication will not interfere with the study procedures
             or compromise subject safety. Some examples of exceptions (permitted medications) are:
             Stable dose of anti-hypertensive medication for at least 3 months prior to the
             screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for
             at least 3 months prior to the screening visit; Antacids up to 24 hours prior to
             dosing.

          -  Participation in the study would result in loss of blood or blood products in excess
             of 500 milliliter (mL) within 3 months.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 3 months, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  Participation in a previous clinical trial with danirixin within 1 year prior to the
             first dosing day in the current study.

          -  Female Subjects: Positive urine beta-human chorionic gonadotropin (beta-hCG) test at
             screening.

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C
             antibody test result at screening.

          -  Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3
             months prior to first dose of study treatment.

          -  For potent immunosuppressive agents, presence of the Hepatitis B core antibody (HBcAb)
             should also lead to exclusion from the study even if HBsAg is negative.

          -  Positive pre-study drug/alcohol screen.

          -  Positive human immunodeficiency virus (HIV) antibody test.

          -  Regular use of known drugs of abuse.

          -  Regular alcohol consumption within 6 months prior to the study defined as: an average
             weekly intake of >21 units for males or >14 units for females. One unit is equivalent
             to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of
             wine or 1 (25 mL) measure of spirits.

          -  Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or
             pummelos, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the
             first dose of study treatment until collection of the final blood sample.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 90 days prior to screening.

          -  Sensitivity to heparin or heparin-induced thrombocytopenia.

          -  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.