Dexpramipexole Renal PK Study

Study Overview
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Brief Summary
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This is a multicenter, open-label, single-dose, PK and safety study in subjects with various stages of renal impairment.

Detailed Description
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Dexpramipexole (BIIB050, KNS-760704; (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydrochloride monohydrate) is a synthetic amino-benzothiazole. Data from multiple in vitro and in vivo assays have suggested that dexpramipexole is neuroprotective. It is being investigated for the treatment ALS. As dexpramipexole is principally eliminated from the body by the kidneys a single oral dose of dexpramipexole will be administered to subjects with various stages of renal impariment comprising the following categories: mild, moderate, severe and ESRD subjects. Healthy volunteers will be matched to each catergory of renal impaired subjects.

Official Title
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A Multicenter, Open-Label, Single-dose, Pharmacokinetic and Safety Study of Dexpramipexole (BIIB050) in Healthy Subjects and Subjects With Renal Impairment

Conditions
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Amyotrophic Lateral Sclerosis, Renal Insufficiency

Intervention / Treatment
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* Drug: Dexpramipexole (dose 1)
* Drug: Dexpramipexole (dose 2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males/females aged 18 to 75 years inclusive and between 19 and 36 kg/m2 inclusive BMI. Subjects with renal impairment must have stable renal disease (i.e., no change in disease status within the 28 days prior to dosing) as determined by the Investigator with laboratory and clinical findings that support the diagnosis of renal impairment. Subjects with renal impairment (excluding ESRD subjects), must have 2 separate estimates of creatinine clearance that are within 25% of each other, obtained >5 days apart, but not >6 months apart Subjects must have a GFR (estimated GFR; as defined by estimation of creatinine clearance using the MDRD formula) of ≥80 (healthy volunteers), between 50 and 79 (mild renal impairment), between 30 and 49 (moderate renal impairment), or <30 (severe renal impairment), or must require dialysis ≤3 times a week (ESRD). Healthy volunteers must be matched to renally impaired subjects for age (± 10 years), gender, and if possible BMI (± 20%). Exclusion Criteria: Healthy volunteers who have received prescription medication within the 14 days prior to dosing (except for birth control). Renally impaired subjects who have received prescription medication within the 14 days prior to dosing (except for birth control and medications taken at a stable dose for underlying conditions, as determined by the Investigator).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexpramipexole (dose 1)<br>Subjects with mild or moderate renal impairment. | Drug: Dexpramipexole (dose 1)<br> <br> * Other names: BIIB050;|
| Experimental: Dexpramipexole (dose 2)<br>Subjects with severe renal impairment and end stage renal disease (ESRD). | Drug: Dexpramipexole (dose 2)<br> <br> * Other names: BIIB050;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC after single dose of dexpramipexole |  | pre dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours after dosing in all subjects, and in addition at 96, 120, and 144 hours after dosing in subjects with severe renal impairment and ESRD. | 
| Cmax after single dose of dexpramipexole |  | pre dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours after dosing in all subjects, and in addition at 96, 120, and 144 hours after dosing in subjects with severe renal impairment and ESRD. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mointoring of Clinical Laboratory tests |  | pre-144 hours post dose | 
| ECG Monitoring |  | pre-144 hrs post dose | 
| Vital Sign monitoring |  | pre-144 hrs post dose | 
| AE monitoring |  | pre-144 hrs post dose |