Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 4-Week, Phase II, Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled, Parallel-Group, Multi-Center Study to Evaluate the Safety, Efficacy and Pharmacokinetics of GSK1278863 in Japanese Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease
Brief Summary: This study aims to characterize the relationship between dose of GSK1278863 and hemoglobin (Hgb) response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease (CKD). It is anticipated that the data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials. This study will consist of a screening phase of 3-9 weeks, a 4-week treatment phase and a follow-up visit approximately 4 weeks after completing treatment.


Options:
A: Inclusion Criteria:

* Subject must be 18 to 99 years of age inclusive, at the time of signing the informed consent.
* Use of any approved rhEPO or analog for at least 8 weeks prior to the screening visit and continuing during the screening period until randomization (Day 1).
* Hgb concentration (measured by HemoCue) within the following range: Week -4: Hgb 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). If Hgb is 11.6 to 11.9 grams/deciliter (7.2 to 7.4 millimoles/liter), up to two retests are allowed; the retest value must be between 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). Day 1: Hgb 8 to 11 grams/deciliter (5 to 6.8 millimoles/liter) and receiving at least the minimum rhEPO or analog dose 3. Hgb\>11 to 11.5 grams/deciliter (6.8 to 7.1 millimoles/liter) and receiving greater than the minimum rhEPO or analog dose 3.
* On hemodialysis (including hemofiltration or hemodiafiltration) \>90 days prior to screening and continuing during the screening period.
* On hemodialysis (in-center) \>=3 times per week.
* Male and female subjects are eligible. 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 from at least 28 days prior to first dose of study treatment and for at least 28 days after the last dose of study treatment.
* Capable of giving signed informed consent.
* In France, a subject will be eligible for inclusion in this study if he or she is either affiliated to or beneficiary of a social security category.

Exclusion Criteria:

* Planned living-related or living-unrelated kidney transplant within 52 weeks after randomization (Day 1).
* Ferritin: \<=100 nanograms/milliliter (\<=100 micrograms/liter), at screening.
* Transferrin saturation (TSAT): \<=20 percent, at screening. If TSAT is 18 to 20 percent, then a retest using a new blood sample can be obtained within 7 days of the final laboratory report; the final retest value must be \>20 percent to confirm eligibility.
* Aplasias: History of bone marrow aplasia or pure red cell aplasia.
* Conditions, other than anemia of CKD, which can affect erythropoiesis.
* Myocardial infarction (MI) or acute coronary syndrome within 8 weeks prior to screening through to randomization (Day 1).
* Stroke or transient ischemic attack within 8 weeks prior to screening through to randomization (Day 1).
* Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
* Current uncontrolled hypertension as determined by the investigator that would contraindicate the use of rhEPO.
* Bazett's correction of QTc interval (QTcB): at Day 1: QTcB \>500 milliseconds, or QTcB \>530 milliseconds in subjects with bundle branch block. There is no QTc (corrected QT) exclusion for subjects with a predominantly ventricular paced rhythm.
* Liver Disease: presence of any one of the following liver-related laboratory values or conditions, at screening, is exclusionary: ALT \>2x upper limit of normal (ULN); Bilirubin \>1.5x ULN; or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
* Evidence of actively bleeding gastric, duodenal or esophageal ulcer disease OR clinically significant gastro intestinal bleeding \<= 8 weeks prior to screening through to randomization (Day 1).
* History of malignancy within 2 years prior to screening through to randomization (Day 1), currently receiving treatment for cancer, or complex kidney cyst (e.g., Bosniak Category IIF, III or IV) \>3 centimeters.
* Use of a strong inhibitor of Cytochrome P4502C8 \[CYP2C8\] (e.g. gemfibrozil) or a strong inducer of CYP2C8 (e.g. rifampin/rifampicin).
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (daprodustat) or epoetin alfa.
* Use of another investigational agent within 30 days or within five half-lives of the investigational agent (whichever is longer) or currently participating in a study of an investigational device prior to screening through to randomization (Day 1).
* Any prior treatment with daprodustat for treatment duration of \>30 days.
* 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 (e.g. intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
B: Inclusion Criteria:

* Age (Informed concent): Japanese \>=20 years of age
* Gender (Screening 2 verification only): Female and male
* Females: must be of childbearing potential, and must agree to use one of the approved contraception methods from Screening 2 until completion of the Follow-up Visit. OR Of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone 23.0 - 116.3 million international units (MIU)/millilitre (mL) and estradiol \<= 10 picograms (pg)/mL is confirmatory\]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved 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 enrolment. For most forms of HRT, at least 2 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Males: must agree to use one of the approved contraceptive methods from the time of Screening 2 until completion of the Follow-up Visit.
* Corrected QT interval (QTc) (Screening 2 verification only): Bazett's Correction of QT Interval (QTcB) \<470 milliseconds (msec) or QTcB \<480 msec in subjects with bundle branch block. There is no QTc inclusion criterion for a subject with a predominantly paced rhythm.
* Dialysis frequency: On hemodialysis (HD) three times weekly for at least 8 weeks prior to Screening 2 through Day 1.
* Dialysis adequacy (Screening 2 only): A single-pool Kt/Vurea of 1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%.
* Hemoglobin: Target stable Hgb between 9.5-12.0 g/dL at screening.
* Stable erythropoiesis-stimulating agent (ESA) dose (Screening 2 only): Using the same ESA (epoetins or their biosimilar, or darbepoietin) with total weekly doses that varied by no more than 50% during the 4 weeks prior to Screening 2.
* Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) (\<100 milligrams \[mg\]/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Screening 2, and Screening 2 through Week 4.

Exclusion Criteria:

* Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
* Renal transplant: Renal transplant anticipated or scheduled within the study time period.
* High ESA dose (Screening 2 verification only): As defined by an epoetin dose of \>=360 IU/kilograms (kg)/week IV or darbepoetin dose of \>=1.8 micrograms (μg)/kg/week IV within the prior 8 weeks through Screening 2.
* methoxy polyethylene glycol epoetin beta (Screening 2 verification only): Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Screening 2.
* Vitamin B12: At or below the lower limit of the reference range
* Folate: \<2.0 nanograms (ng)/mL (\<4.5 nanomoles \[nmol\]/liters \[L\])
* Iron status: Ferritine \<100 ng/mL (\<100 μg/L) AND Transferrin saturation (TSAT) \<20%
* Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening 2 through Day 1.
* Stroke or transient ischemic attack: Within the 8 weeks prior to Screening 2 through Day 1.
* Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system or symptomatic right heart failure diagnosed prior to Screening 2 through Day 1.
* Hypertension: Defined using pre-dialysis vitals of diastolic blood pressure \>100 mmHg or systolic blood pressure \>170 mmHg.
* Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), except vascular access thrombosis, within the 8 weeks prior to Screening 2 through Day 1
* Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months or macular edema requiring treatment..
* Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Screening 2 through Day 1.
* Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia other than renal disease diagnosed prior to Screening 2 through Day 1.
* Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests \[alanine transaminase (ALT) or aspartate transaminase (AST) \>2.0 x upper limit of normal (ULN) or total bilirubin \> 1.5 x ULN\]; or other hepatic abnormalities that in the opinion of the investigator (subinvestigator) would preclude the subject from participation in the study.
* Major surgery: Major surgery (excluding vascular access surgery) within the prior 8 weeks, within the Screening 2 to Day 1 or planned during the study.
* Transfusion: Blood transfusion within the prior 8 weeks, within the Screening 2 to Day 1 or an anticipated need for blood transfusion during the study.
* Gastrointestinal (GI) bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Screening 2 through Day 1.
* Acute infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within 8 weeks prior to Screening 2 through Day 1.
* Malignancy: Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have a strong family history of cancer (e.g., familial cancer disorders); with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to Screening 2 through Day 1.
* Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product
* Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Screening 2 until the Follow-up Visit.
* Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Screening 2 through Day 1.
* Pregnancy or lactation: Pregnant females as determined by positive serum Human Chorionic Gonadotrophin (hCG) test (Screening 2 only) OR women who are lactating at Screening 2 and/or Day 1 or during the trial.
* Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator would consider inappropriate to participate in the study.
C: Inclusion Criteria:

* - Subjects are eligible if they meet all of the inclusion criteria below:
* General criteria
* Age: \>=18 years of age. (Week -4 verification only)
* Gender: Female and male subjects. (Week -4 verification only) Females: If of childbearing potential, must agree to use one of the approved contraception methods, from Screening until completion of the Follow-up Visit OR of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 International units per liter (IU/L) and estradiol \<=10 picomole per liter (pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved 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 enrolment. For most forms of HRT, at least 2 weeks must elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method;
* Q-T Interval Corrected for Heart Rate (QTc): Bazett's Correction of QT Interval (QTcB) \<470 millisecond (msec) or QTcB \<480 msec in subjects with bundle branch block. There is no QTc inclusion criterion for a subject with a predominantly paced rhythm.
* CKD-related criteria
* Dialysis frequency: On hemodialysis (HD) three to five times weekly for at least 4 weeks prior to Week -4 Screening through Week 4. NOTE: Combination methods including hemofiltration (HF) or ultrafiltration (UF) with HD are allowed. However, the type of dialysis (HD, hemodiafiltration (HDF) or UF) should not change during the study.
* Dialysis adequacy: A single-pool dialyzer clearance multiplied by dialyzer time divided by volume of distribution of urea (Kt/Vurea) of \>=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%. NOTE: Only needs confirming at Week -4.
* Hemoglobin: Baseline Hgb of 9.0-11.5 g/dL (may rescreen in a minimum of 2 weeks).
* Stable rhEPO dose: Using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses varying by no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization), confirm that total weekly doses varied by no more than 50% during the screening period.
* Iron replacement therapy: Subjects may be on stable maintenance oral or IV (\<=100 mg/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.

Exclusion Criteria:

* Subjects are not eligible if they meet any of the exclusion criteria below:
* CKD-related criteria
* Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
* Renal transplant: Pre-emptive or scheduled renal transplant.
* High rhEPO dose: An epoetin dose of \>=360 IU/Kg/Week IV or \>=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of \>=1.8 microgram (µg)/Kg/Week IV or SC within the prior 8 weeks through Day 1 (randomization).
* Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Day 1 (randomization).
* Laboratory test-based criteria (Week -4 verification only)
* Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
* Folate: \<2.0 nanogram (ng)/mL (\<4.5 nanomole (nmol)/L) (may rescreen in a minimum of 4 weeks).
* Ferritin: \<100 ng/mL (\<100 Micrograms per liter).
* Transferrin saturation (TSAT): Outside of the reference range.
* Cardiovascular disease-related criteria
* Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
* Stroke or transient ischemic attack: Within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
* Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Week -4 Screening through Day 1 (randomization); Symptomatic right heart failure diagnosed prior to Week -4 Screening through Day 1 (randomization).
* Hypertension: Defined using pre-dialysis vitals (Week -4, Day 1) of diastolic blood pressure (DBP) \>100 millimeters of mercury (mmHg) or systolic blood pressure (SBP) \>170 mmHg.
* Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), except vascular access thrombosis, within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
* Other disease-related criteria
* Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam.
* Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Week -4 Screening through Day 1 (randomization).
* Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 (randomization).
* Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests \[alanine transaminase (ALT) or aspartate transaminase (AST) \> 2.0 x upper limit of normal (ULN) or total bilirubin \> 1.5 x ULN\]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study. NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met.
* Major surgery: Major surgery (excluding vascular access surgery) within the prior 8 weeks, during the Week -4 Screening phase or planned during the study.
* Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study.
* GI Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
* Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
* Malignancy: Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have a strong family history of cancer (e.g., familial cancer disorders); with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to Week -4 Screening through Day 1 (randomization).
* Concomitant medication and other Investigational Product-related criteria
* Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
* Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Week -4 Screening until the Follow-up Visit.
* Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Week -4 Screening through Day 1 (randomization).
* 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.
* Pregnancy or Lactation: Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or during the trial.
* Other Eligibility Criteria Considerations
* Laboratory eligibility criteria will be assessed according to the central laboratory results for the screening samples.
* Subjects who fail screening may be rescreened as soon as the investigator feels they may have become eligible. However, an individual subject may not rescreen more than twice. There is no predetermined amount of time that the investigator needs to wait to rescreen a previously ineligible subject, except those excluded for Hgb or folate who may only rescreen in 2 and 4 weeks, respectively, and those excluded for Vitamin B12 who may rescreen in 8 weeks
D: Inclusion Criteria:

1. Ability to understand and give informed consent for participation. 2. Hemoglobin values during the screening period must be 8-11 g/dL (both inclusive).

3.

1. Patients will be considered not treated with erythropoietin analogue (Epoetin and Darbepoeitin) if they have not received erythropoietin analogue for at least 4 weeks and Mircera® for at least 8 weeks prior to screening visit. OR
2. Patients who are on ESA therapy must be on stable dose for 4 weeks prior to enrollment (≤30% of dose change).

   4. Patients on hemodialysis (≥2 times in a week) for at least 12 weeks prior to screening visit and have access consisting of an arteriovenous fistula, AV graft, or catheter (permanent/temporary).

   5. Patients with no planned change in dialysis modality and with no planned renal transplant during study period.

   6. Left ventricular ejection fraction ≥40% by echocardiogram prior to randomization.

   7. No iron, folate or Vitamin B12 deficiency.

   8. Females of childbearing potential, must agree to use one of the approved contraception methods, from screening until completion of the follow-up visit.

   Exclusion Criteria:
   1. Red blood cell transfusion within 8 weeks prior to participating in the study.
   2. History of previous or concurrent cancer.
   3. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection.
   4. Active infection at initiation of study.
   5. History of renal transplant.
   6. Uncontrolled hypertension (defined as SBP \>180 mmHg or DBP \>100 mmHg) at screening visit (before dialysis).
   7. Patient on high rhEPO dose at screening visit. \[High dose defined as an epoetin dose of ≥450 IU/kg/week intravenous or ≥ 300 IU/kg/week subcutaneous or darbepoetin dose of ≥1.5 µg/kg/week subcutaneous\].
   8. Major surgery within 90 days of the first day of study drug dosing, and minor surgery within 30 days of the first day of study drug dosing.
   9. Unable to swallow tablets or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.
   10. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia.
   11. Presence or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal \[GI\] bleeding or constitutional disorders) that may increase risk of life-threatening bleeding.
   12. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
   13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Desidustat or Epoetin alfa or to any erythropoieisis-stimulating agent.
   14. Pregnant and breastfeeding women.
   15. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.
   16. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation.
   17. Presence of other clinically significant systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) which, in the Investigator's opinion, could compromise the patient's safety.
   18. History of significant alcoholism or drug abuse within the past 1 year. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).
   19. History of difficulty with donating blood.
   20. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening.
   21. Participants who have participated in any drug research study other than the present trial within past 3 months.
   22. Participants who have donated one unit (350 ml) of blood in the past 3 months or history of whole blood transfusion in last 120 days prior to entry in the study.
   23. Existing clinically active chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease)
   24. In case of DM patients, HbA1c \>9%.
   25. Female volunteers with following criteria will not be recruited:

       * History of pregnancy or lactation in the past 3 months
       * Fertile female volunteers not protected against pregnancy by adequate long- term anti-fertility measures
       * History of less than 1 year of menopause and not using adequate long-term anti-fertility measures
       * Positive urine pregnancy test at Visit 2
       * Positive serum β-hCG level at the screening visit
   26. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or history of myocardial infarction prior to first dose with study drug.

Answer: B