This is a multi-center, two-part study; Part A and Part B. Part A of the study is an open-label, single-dose pharmacokinetic (PK) evaluation of 100 mg RVX000222 on dialysis and non-dialysis days in eight (8) End Stage Renal Disease (ESRD) patients who receive hemodialysis as standard of care.

Part B of the study is a double-blind, placebo-controlled study in up to thirty six (36) ESRD patients receiving hemodialysis using a sequential cross-over design with RVX000222 at a daily oral dose of 100 mg b.i.d. (200 mg per day) or matching placebo in combination with SoC.

The primary objective of the study is to evaluate if treatment with RVX000222 in combination with standard of care (SoC) decreases plasma alkaline phosphatase in comparison to placebo and SoC.

Inclusion Criteria:

1. Men or women ≥18 and ≤80 years of age.

2. Diagnosis of end-stage renal disease and receiving hemodialysis an average of three (3) times per week for at least ninety (90) days prior to Enrollment/Visit 2.

3. Clinically stable, in the judgment of the investigator.

4. Female subjects must meet one of the following:

   1. If of childbearing potential, must have a negative serum pregnancy test and be willing and able to use medically acceptable non-hormonal method of birth control (non-hormonal intrauterine device, condom, or diaphragm) or remain abstinent from Screen until Follow-up Visit, or
   2. Be of non-child-bearing potential: post-surgical sterilization (hysterectomy or a bilateral oophorectomy) or post-menopausal. Post-menopausal is defined as amenorrhea for ≥2 years at Screen/Visit 1.

5. In the view of the investigator, during the course of the trial, subject is expected to:

   1. remain on unchanged standard of care medication from 4 weeks prior to Enrollment/Visit 2.
   2. not require hospitalization for any condition other than routine hemodialysis.

6. Have given signed informed consent to participate in the study.

Exclusion Criteria:

1. Planned major surgery in the next 4 months, including renal transplant, from Enrollment/Visit 2.

2. Major surgery, in the judgement of the investigator, within 12 weeks before enrollment/Visit 2 (excluding vascular access surgery).

3. Hospitalization for congestive heart failure, myocardial infarction, deep vein thrombosis, stroke or transient ischemic attack or peripheral arterial disease within 6 months before Enrollment/Visit 2.

4. New York Heart Association (NYHA) Classification, Class III or IV Heart Failure at Screen/Visit 1.

5. Diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg during screen.

6. Currently receiving antibiotic therapy for systemic infection.

7. In the judgement of the Investigator, evidence of active hepatitis. Hepatitis serology testing will be performed at Screen/Visit 1.

8. History of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

9. Red blood cell (RBC) transfusions within 12 weeks before Enrollment/Visit 2.

10. Current or recent (within 12 months prior to Visit 1) treatment with immunosuppressants (e.g., cyclosporine).

11. Use of fibrates at any dose or niacin/nicotinic acid 250 mg or more within 30 days prior to Screen/Visit 1.

12. Diagnosis of systemic hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia).

13. Hemoglobin <9.5 g/dL at Screen/Visit 1.

14. Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN) at Screen/Visit 1.

15. Bilirubin >1.0 x ULN at Screen/Visit 1.

16. Pregnant or breast-feeding women.

17. Any condition which, in the opinion of the investigator, may place the subject at higher risk from his/her participation in the study, or is likely to prevent the subject from complying with the requirements of the study or completing the study.

18. Treatment with an investigational agent or device within 30 days or 5 half-lives before Enrollment/Visit 2 or scheduled to receive an investigational agent other than those specified by this protocol during the course of this study.

19. History of noncompliance with medical regimens or unwillingness to comply with the study protocol.

20. In the judgement of the Investigator, any disorder that may impact the ability to give informed consent for participation in this study.

21. Any condition that, in the opinion of the investigator, would confound the evaluation and interpretation of efficacy and/or safety data.

22. Persons directly involved in the execution of this protocol.

    Exclusion Criteria, Part A Only:

23. Are unwilling to abstain from alcoholic beverages, caffeine or xanthine-containing products (e.g., tea, coffee, chocolate, cola), and use of nicotine products from 24 hours prior to Clinical Research Unit (CRU) admission to 48 hours post RVX000222 dose administration.

Exclusion Criteria, Part B Only:

23. Parathyroid hormone, intact (PTH, intact) <150 pg/mL or >800 pg/mL at Screen/Visit 1.