Dexpramipexole Renal PK Study

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

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

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency; Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Dexpramipexole (dose 1); Drug: Dexpramipexole (dose 2)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Research Site
  • Minnesota
    • Brooklyn Center, Minnesota, United States, 55430
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Knopp Biosciences

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 26, 2011

Study Record Updates

• Last Update Posted (Estimate): November 25, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Renal Insufficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 223RI101