Efficacy and Safety Study of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents
Condition: Anaemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Intervention: GSK1278863; Iron
Intervention description: GSK1278863 will be provided as round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, 4 mg or 6 mg of GSK1278863 as active ingredient.; Subjects will receive supplemental iron therapy if ferritin is <=100 ng/mL and TSAT is <=20%. The investigator (or subinvestigator) will choose the route of administration and dose of prescription iron.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: efficacy; hemodialysis (HD); hemoglobin (Hgb); erythropoiesis-stimulating agents (ESAs); GSK1278863

Summary:

      This 24-week, Phase 3, open-label, non-comparative, multicentre study aims to evaluate the
      efficacy and safety of GSK1278863 in Japanese hemodialysis (HD) patients with renal anemia
      not using erythropoiesis-stimulating agents (ESAs). The primary objective is to evaluate the
      initial response to GSK1278863 measured by hemoglobin (Hgb) levels in HD patients not using
      ESAs enrolled in this study. The study is designed to evaluate the appropriateness of the
      starting dose of GSK1278863 and of the GSK1278863 dose adjustment regimen to achieve or
      maintain the target Hgb levels. This study will consist of a 4-week screening period, a
      24-week treatment period (4-week fixed-dose period and a 20-week dose adjustment period), and
      a 2- to 4-week follow-up period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age (at the time of informed consent): >=20 years

          -  Dialysis: Patients on hemodialysis (HD) or hemodiafiltration (HDF)

          -  Use of any erythropoiesis stimulating agent (ESA): Newly started dialysis (Dialysis
             newly started <12 weeks before screening): Patients not using ESAs after the start of
             dialysis; Maintenance dialysis (Dialysis started >=12 weeks before screening):
             Patients not using ESAs within 8 weeks before screening (including interruption of ESA
             therapy)

          -  Hemoglobin (Hgb): >=8.0 to <10.0 g/dL (measured using a point-of-care Hgb measurement
             device at the study site on Day 1)

          -  Iron parameter: Ferritin >100 nanograms (ng)/milliliter (mL) or transferrin saturation
             (TSAT) >20% (at screening only)

          -  Gender (at screening only): Female or male.

        A female subject is eligible to participate if she is not pregnant (as confirmed by a
        negative serum human chorionic gonadotropin [hCG] test for females of reproductive
        potential [FRP] only), not breastfeeding, and at least one of the following conditions
        applies:

          -  Females of non-reproductive potential defined as: Pre-menopausal with one of the
             following and no plans to utilise assisted reproductive techniques (example [e.g.], in
             vitro fertilisation or donor embryo transfer): documented bilateral tubal ligation or
             salpingectomy; documented hysteroscopic tube occlusion procedure with follow-up
             confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral
             oophorectomy

          -  Post-menopausal defined as females 60 years of age or older or In females <60 years of
             age, 12 months of spontaneous amenorrhea (In questionable cases, a blood sample with
             simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with
             menopause is confirmatory [the reference values are provided separately]). Females on
             hormone replacement therapy (HRT) and whose menopausal status is in doubt will be
             required to use one of the highly effective contraception methods if they wish to
             continue their HRT during the study. Otherwise, they must discontinue HRT to allow
             confirmation of post-menopausal status prior to study enrollment.

        Females of reproductive potential who agree to follow one of the options listed in the
        "GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in
        Females of Reproductive Potential" from 28 days before the first dose of study treatment
        until completion of the follow-up visit.

          -  Informed consent: Subjects who can provide written informed consent to the study,
             involving compliance with the requirements and patient responsibilities stated in the
             consent form and the protocol.

        Exclusion Criteria:

        CKD related criteria

          -  Kidney transplant: Planned living kidney transplant during the study period
             Anemia-related criteria

          -  Aplasia: History of bone marrow aplasia or pure red cell aplasia

          -  Other causes of anemia: Pernicious anemia, thalassaemia, sickle cell disease, or
             myelodysplastic syndrome

          -  Gastrointestinal bleeding: Evidence of actively bleeding gastric, duodenal, or
             esophageal ulcer disease or clinically significant gastrointestinal bleeding within 8
             weeks before screening or during a period from screening to Day 1.

        Cardiovascular disease-related criteria

          -  History of myocardial infarction, acute coronary syndrome, stroke or transient
             ischemic attack: Diagnosed within 8 weeks before screening or during a period from
             screening to Day 1.

          -  Heart failure: Class IV heart failure, as defined by the New York Heart Association
             (NYHA) functional classification system

          -  Corrected QT interval (QTc) (at screening only): QTc >500 milliseconds (msec), or QTc
             >530 msec in subject with bundle branch block. Note: Corrected QT interval using
             Bazett's formula (QTcB) (machine-read or manually) will be used.

        Other disease-related criteria

          -  Liver disease (if any of the following occurs):

               -  Alanine transaminase (ALT) >2x upper limit of normal (ULN)

               -  Bilirubin >1.5xULN (If bilirubin fractions are measured and direct bilirubin is
                  <35%, isolated bilirubin >1.5xULN will be acceptable.)

               -  Current unstable active liver or biliary disease (generally defined by the onset
                  of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric
                  varices, persistent jaundice, or cirrhosis). Note: The only exception is squamous
                  cell or basal cell carcinoma of the skin that has been definitively treated >=8
                  weeks before screening.

          -  Malignancy: History of malignancy within the two years prior to screening, known
             complex kidney cyst >3 centimeters (cm) (II F, III or IV based on the Bosniak
             classification) or currently receiving treatment for cancer. Note: The only exception
             is squamous cell or basal cell carcinoma of the skin that has been definitively
             treated >=8 weeks before screening.

        Concomitant medications and other study treatment-related criteria

          -  Iron medication: Planned use of any intravenous iron during the screening period or
             from Day 1 to Week 4.

        Note:

          -  Patients on oral iron may be enrolled if the iron dose regimen is unchanged during the
             screening period and from Day 1 to Week 4.

          -  Patients on anti-hyperphosphatemia medication containing iron (e.g., ferric citrate
             hydrate) for at least 12 weeks before screening may be enrolled if the medication is
             continued during the screening and from Day 1 to Week 4.

               -  Severe allergic reactions: History of severe allergic or anaphylactic reactions
                  or hypersensitivity to any excipients in the investigational product

               -  Drugs and dietary supplements: Current use of prohibited prescription drugs,
                  non-prescription drugs, or dietary supplements or planned use of any of these
                  drugs during the study period (prohibited drugs: strong cytochrome P450 (CYP)2C8
                  inducers and inhibitors)

               -  Exposure to any other investigational product: Use of an investigational product
                  within the past 30 days or five half lives of that investigational product
                  (whichever is longer).

               -  Prior treatment with GSK1278863: Prior treatment with GSK1278863 for >30 days
                  General health-related criteria

               -  Other conditions: Any other condition, clinical or laboratory abnormality, or
                  examination finding that the investigator considers would put the subject at
                  unacceptable risk, which may affect study compliance or prevent understanding of
                  the aims or investigational procedures or possible consequences of the study.