Daprodustat Bioequivalence and Food Effect Study
Condition: Anaemia
Intervention: Daprodustat 2 mg tablet; Daprodustat 4 mg tablet
Intervention description: Daprodustat is available as 2 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 2 tablets of 2 mg daprodustat will be administered in a fasted state during Part 1 of the study.; Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study.
Intervention MeSH terms: Glycine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study will be conducted in two parts. Part 1 is the bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet in fasting and fed state in a crossover manner.
Masking: None (Open Label)
Enrollment: 64.0
Sex: Male
Minimum age: 20 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Japan; Crossover; Daprodustat; Bioequivalence; Pharmacokinetics

Summary:

      This is two-way crossover study to compare pharmacokinetic (PK) of daprodustat 2 milligram
      (mg) versus 4 mg tablets and food effect on the PK of daprodustat following single oral doses
      in healthy Japanese male subjects. This study will be conducted in two parts. Part 1 is the
      bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg
      daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is
      Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet
      in fasting and fed state in a crossover manner. There will 5-day wash-out period between each
      intervention period. There will be approximately 52 subjects in Part 1 and 12 subjects in
      Part 2. The study will last for 6 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be 20 to 55 years of age inclusive, at the time of signing the informed
             consent.

          -  Japanese subjects who are overtly healthy as determined by medical evaluation
             including medical history, physical examination, laboratory tests, and cardiac
             monitoring.

          -  Body weight > = 50 kilogram (kg) and body mass index (BMI) within the range 18.5 -
             24.9 kilogram per meter square (kg/m^2).

          -  Male subjects.

          -  Subjects capable of giving signed informed consent.

        Exclusion Criteria:

          -  History or presence of cardiovascular(CV), respiratory, hepatic, renal,
             gastrointestinal (GI), endocrine, haematological, or neurological disorders capable of
             significantly altering the absorption, metabolism, or elimination of drugs;
             constituting a risk when taking the study intervention; or interfering with the
             interpretation of data.

          -  Abnormal blood pressure as determined by the investigator.

          -  ALT >1.5x upper limit of normal (ULN).

          -  Bilirubin >1.5xULN

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QTcF > 500 millisecond (msec). The QTcF is the QT interval corrected for heart rate
             according to Fridericia's formula, machine-read or manually over-read. The specific
             formula that will be used to determine eligibility and discontinuation for an
             individual subject should be determined prior to initiation of the study. In other
             words, several different formulae cannot be used to calculate the QT correction (QTc)
             for an individual subject and then the lowest QTc value used to include or discontinue
             the subject from the trial.

          -  The values of Hgb at screening: >=16.0 gram per deciliter (g/dL).

          -  History of deep vein thrombosis, pulmonary embolism or other thrombosis related
             condition.

          -  History of myocardial infarction (MI) or acute coronary syndrome, stroke or transient
             ischemic attack.

          -  Subjects that have undergone cholecystectomy.

          -  History of malignancy within the prior 2 years or currently receiving treatment for
             cancer.

          -  Any evidence of heart failure, as defined by the New York Heart Association (NYHA)
             functional classification system.

          -  Past or intended use of over-the-counter or prescription medication including
             vitamins, diet foods and herbal medications within 14 days prior to first dosing.

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  Current enrolment or past participation (that is administration of last dose of
             investigational study intervention) within the last 30 days (or 5 half-lives,
             whichever is longer) before signing of consent in this clinical study involving an
             investigational study intervention or any other type of medical research.

          -  The subject with positive serological test for syphilis (Rapid Plasma Reagin [RPR] and
             Treponema pallidum haemagglutination 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:for an
             average weekly intake of >14 units for males. One unit is equivalent to 350 milliliter
             (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.

          -  Smoking or history of regular use of tobacco- or nicotine-containing products (example
             nicotine patch, electronic cigarette) within 6 months prior to screening.

          -  Sensitivity to any of the study interventions, or components thereof, or drug or other
             allergy that, in the opinion of the investigator or medical monitor, contraindicates
             participation in the study.

          -  History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL
             within 1 month prior to the first dosing day.