Study of ISIS 681257 in Patients With Renal Impairment Compared to Healthy Patients

Study Overview
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Brief Summary
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This is a Phase 1, Multicenter, Open-Label, Parallel Group Adaptive Pharmacokinetic Single Dose Study of ISIS 681257 Subcutaneous Injections in Male And Female Subjects with Normal and Impaired Renal Function

Official Title
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Phase 1, Multicenter, Open-Label, Parallel Group Adaptive Pharmacokinetic Single Dose Study Of ISIS 681257 Subcutaneous Injections In Male And Female Subjects With Normal And Impaired Renal Function

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: ISIS 681257


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old BMI 18.5 to 42.0 kg/m2 No known diseases or significant findings on physical exam (normal renal only) eGFR >/= 90 mL/min/1.73m2 (normal renal only) Clinically stable (renal impaired only) eGFR 30-59 mL/min/1.73m2 (renal impaired only) Exclusion Criteria: Females of childbearing potential Conditions or disease that may interfere with study drug Any significant diseases Hypersensitivity to any drugs or similar drugs to those used in the study Drug dependency or abuse Previous exposure to other investigational drug within 28 days Blood donations within 28 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal Renal Function<br>Subjects with normal renal function will be matched by age (±10 years), weight (± 20%), and gender to the pooled mean values of subjects with the moderate renal impairment. Subjects will receive 1 dose of ISIS 681257. | Drug: ISIS 681257<br>* Xmg dose administered as a subcutaneous injection<br>|
| Experimental: Moderate Renal Impairment<br>Presence of moderate renal impairment (eGFR 30-59 mL/min/1.73m2). Subjects will receive 1 dose of ISIS 681257. | Drug: ISIS 681257<br>* Xmg dose administered as a subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of ISIS 681257 following a single subcutaneous dose in subjects with impaired renal function relative to matched, healthy controls with normal renal function. | The plasma concentrations of ISIS 681257 will be measured. | Day 31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse effects of ISIS 681257 in subjects with normal and impaired renal function. | The safety of ISIS 681257 will be assessed by determining adverse effects by dose. Safety results in subjects with renal impairment dosed with ISIS 681257 will be compared with those from healthy subjects dosed with ISIS 681257. | Day 31 | 
| The plasma protein binding of ISIS 681257 in subjects with normal and impaired renal function. | Percent of ISIS 681257 bound to proteins in subjects with renal impairment dosed with ISIS 681257 will be compared with those from healthy subjects dosed with ISIS 681257. | Day 1 |