End-stage Renal Disease (ESRD)
Conditions
Brief summary
Evaluation of safety, tolerability, PK and PD of ISIS 416858 in patients with end-stage renal disease (ESRD) receiving chronic hemodialysis.
Detailed description
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.
Interventions
DRUGISIS 416858
subcutaneous injection
DRUGPlacebo
subcutaneous injection
Sponsors
Bayer
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability - evaluated by reviewing frequency and severity of Adverse events (including bleeding events) and use of concomitant medications, changes in vital signs and laboratory evaluations for all patients | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | The safety and tolerability of ISIS 416858 will be evaluated by reviewing frequency and severity of Adverse events (including bleeding events) and use of concomitant medications, changes in vital signs and laboratory evaluations for all patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Outcomes in aPTT as measured by absolute change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by absolute change over time for aPTT (seconds) |
| Pharmacodynamic Outcomes in aPTT as measured by percent change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by percent change over time for aPTT (seconds) |
| Pharmacodynamic Outcomes for PT and the PT derived INR as measured by absolute change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by absolute change over time for PT (seconds) and the PT derived INR (International Normalization Ratio) |
| Pharmacodynamic Outcomes for PT and the PT derived INR as measured by percent change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by percent change over time for PT (seconds) and the PT derived INR (International Normalization Ratio) |
| Pharmacodynamic Outcomes in FXI antigen and activity as measured by absolute change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by absolute change over time for FXI antigen and activity (units/milliliter) |
| Pharmacodynamic Outcomes in FXI antigen and activity as measured by percent change over time. | For the PK Cohort: Patients will be followed for 72 days. For Cohorts A and B: Patients will be followed for 162 days. | Pharmacodynamic Outcomes as measured by percent change over time for FXI antigen and activity (units/milliliter) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Outcome for Cohorts A and B to assess steady state concentrations | Patients will be followed for 162 days for this outcome measure | Plasma will be collected at each dosing interval to assess steady state concentrations. |
| Pharmacokinetic Outcome for PK Cohort of effect of dialysis on peak concentrations | Patients will be followed for 29 days for this outcome measure. | Effect of dialysis on peak concentrations post single dose drug administration. |
| Pharmacokinetic Outcome for PK Cohort of effect of dialysis on partial area under the plasma concentration-time curve | Patients will be followed for 29 days for this outcome measure. | Effect of dialysis on partial area under the plasma concentration-time curve post single dose drug administration (AUC 0-24hr). |
Countries
Canada
Outcome results
None listed