Amendment 1 Revisions: 1. Updated List of Abbreviations (p. 8-9). 2. Corrected typographical errors in Table 1: Part A - Schedule of Events/Evaluations (p. 30). 3. Revised Section 11.6, Unblinding Upon Completion of Part A (p. 131) to clarify that primary and secondary efficacy analyses will be conducted after the Part A data base is locked and will not be modified; and to clarify that exploratory analyses that do not involve the primary or secondary efficacy analyses are subject to modification. 4. Added the following exploratory endpoints to Parts A and B: Part A 15. EuroQol 5D-5L Health Questionnaire (EQ-5D-5L). 16. Treatment Satisfaction Questionnaire for Medication (TSQM 9) (evaluated at Weeks 6 and 24). Part B 11. EQ-5D-5L. 12. TSQM 9 (evaluated at Week 76).

Amendment 2 Revisions: 1. Revised Exclusion Criteria (EC) #24 to delete “including any history of hepatic or renal failure” (p. 22; p. 55). 2. Added EC #27: “Patients with moderate to severe hepatic or renal impairment.” (p. 22; p. 55). 3. Added EC #28: “Patients who have taken strong CYP3A4 inhibitors or inducers within 4 weeks prior to Baseline (Visit 2) or who anticipate requiring the use of strong CYP3A4 inhibitors or inducers during the duration of the trial (see Section 5.9.2 and Appendix 15.15)” (p. 22; p. 55). 4. Added EC #29: “Patients with pacemakers or implantable cardioverter defibrillators” (p. 22; p. 55). 5. Added to Section 4.3.2, Definite Criteria for Withdrawal from Study: “9. Patients noted to have an elevated BP post-baseline, with a systolic BP ≥ 160 mmHg and/or a diastolic BP≥ 100 mmHg that is present at 2 consecutive post-baseline study visits” (p. 57). 6. Added to Section 5.9.2, Prohibited Concomitant Medications/ Treatments, regarding medications prohibited throughout the study (Parts A and B): “Strong CYP3A4 inhibitors or inducers. Refer to Appendix 15.15” (p. 61). 7. Added paragraph at end of Section 9.5.1, Blood Pressure and Pulse Measurements: “Patients noted to have an elevated BP post-baseline, with a systolic BP ≥ 160 mmHg and/or a diastolic BP ≥ 100 mmHg that is present at 2 consecutive post-baseline study visits, will be discontinued from study (see Section 4.3.2)” (p. 118). 8. Added Appendix 15.15, Prohibited CYP3A4 Inhibitors and Inducers (p. 183).

Amendment 3 Revisions 1. Updated company name, email addresses and telephone numbers of Study Director, and Chief Medical Officer in multiple places. 2. Updated Study Contact Information 3. Updated safety reporting fax number 4. Added to Abbreviations ANC (absolute neutrophil count), WBC (white blood cells) 5. Inserted into Parts A and B procedures additional blood draws for hematology. 6. Added Tables 1.1 (Part A – Schedule of Events/ Evaluations for Hematology Monitoring) and 2.1 Part B – Schedule of Events/ Evaluations for Hematology Monitoring. 7. Inserted into Criteria for Patient Discontinuation a lower limit for absolute neutrophils. 8. Added the following as section 6.2.6 a Visit 3.5 (Week 4). 9. Inserted section 6.2.9 a Visit 4.3 (Week 8). 10. Inserted section 6.2.10 a Visit 4.8 (Week 10) 11. Section 6.2.12: Clarified the next visit by number and differentiates next blood draw (visit 16) and telephone call (visit 18). 12. Insert section 6.2.13 a Visit 5.5 (Week 16) 13. Insert section 6.2.16 a Visit 6.5 (Week 22)