A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis
A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis
Evaluation of safety, tolerability, PK and PD of ISIS 416858 in patients with end-stage renal
 disease (ESRD) receiving chronic hemodialysis.
Evaluation of Safety, PK and PD of ISIS 416858 in patients with end-stage renal disease
 (ESRD) receiving chronic hemodialysis.

 The overall objectives are to evaluate the safety, tolerability, pharmacokinetics, and
 pharmacodynamics of ISIS 416858 in ESRD patients on hemodialysis.
Inclusion Criteria:

 -  End stage renal disease maintained on outpatient hemodialysis at a healthcare center
 for > 3 months from screening with hemodialysis using heparin (unfractionated heparin
 or low-molecular weight heparin) 3 times per week for a minimum of 3 hours per
 dialysis session and plan to continue this throughout the study.

 Exclusion Criteria:

 -  Documented thrombotic event (acute coronary syndrome, stroke or transient ischemic
 attack, venous thromboembolic event) in the past 3 months.

 -  Active bleeding within the past 3 months from screening or documented bleeding
 diathesis (history of bleeding disorder) or Screening values of:

 -  Platelet count < 150,000 cells/mm3

 -  INR > 1.4

 -  aPTT > upper limit of normal (ULN)

 -  Abnormal liver function at Screening:

 -  ALT or AST > 2 x ULN

 -  Total bilirubin > ULN

 -  Concomitant medication restrictions: Concomitant use of anticoagulant/antiplatelet
 agents (e.g., dabigatran, rivaroxaban, clopidogrel) that may affect coagulation
 (except low dose aspirin (≤ 100 mg/day) during Treatment and Post-treatment Evaluation
 Periods is not allowed.

 -  Uncontrolled hypertension as judged by the Investigator. Patients with a pre- or
 post-dialysis blood pressure (BP) that is > 160 mmHg on at least 3 of last 5 dialysis
 treatments.

 -  Planned major surgery in the next 6 months (e.g. renal transplant surgery)