Pharmacokinetics (PK) of Dalfampridine-ER 7.5 mg BID in Healthy Volunteers and Subjects With Mild or Moderate Renal Impairment

Study Overview
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Brief Summary
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The steady-state pharmacokinetics of Dalfampridine-ER (extended release) 7.5 mg (milligram) tablets in healthy adult volunteers and those with mild and moderate renal impairment, and examine between group comparisons.

Detailed Description
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Pharmacokinetics in normal, mildly renally impaired, and moderately renally impaired subjects

Official Title
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A Parallel, Three Arm, Open-label, Multi-dose Pharmacokinetic Study of Dalfampridine-ER 7.5 mg Twice Daily in Both Healthy Volunteers and Those With Mild and Moderate Renal Impairment

Conditions
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Renal Insufficiency

Intervention / Treatment
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* Drug: Dalfampridine-ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender between the ages of 18 and 75 years Have a body mass index (BMI) ranging between 18.5 - 35.0 kg/m2, inclusive Have adequate cognitive function to understand and sign the IRB approved informed consent prior to the performance of any study-specific procedures Be willing and able to comply with all trial requirements Fit into one of three 12-subject groups: normal renal function (CrCl > 80 mL/min), mild renal impairment (CrCl 51-80 mL/min), and moderate renal impairment (CrCl 30-50 mL/min) Have sufficient venous access to permit blood sample collection Women of childbearing potential must have a negative β-HCG pregnancy test at the Screening Visit. Exclusion Criteria: Women who are either pregnant or breastfeeding, and women of childbearing potential (i.e., has not had a hysterectomy or bilateral oophorectomy, or is not at least two years postmenopausal) who are engaged in active heterosexual relations and not using any of the following birth control methods: tubal ligation, implantable contraception device, oral, patch or injectible contraceptive, double barrier method, or sexual activity restricted to a vasectomized partner; History of seizure(s); Unstable, acute, or severe (CrCl < 30 mL/min) renal failure; Clinically significant abnormal findings on the physical examination, ECG, vital signs, medical history, or clinical laboratory results during screening (other than abnormal renal values); Any unstable cardiovascular, enterohepatic, respiratory, or immunologic disorder or disease that may substantially affect the pharmacokinetics of Dalfampridine-ER; Known allergy to pyridine-containing substances, or any of the inactive ingredients of the Dalfampridine-ER tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide); Participation in an investigational drug trial 30 days prior to Screening or plans to enroll in an investigational drug trial at any time during this study; Any medical condition including psychiatric disease that would interfere with the interpretation of the study results or the conduct of the study; Subject has started a new medication (prescription, vitamins, herbal medications, or other over-the-counter medications), or had a change in their existing medication within 30 days prior to screening; History of drug or alcohol abuse in the past 2 years, or tests positive for drugs of abuse at Screening; Donation of blood or blood components within 30 days prior to administration of investigational drug. The Investigator should instruct subjects who participate in this study not to donate blood or blood components during their participation in the study and up to four weeks after the completion of the study.

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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Accepts Healthy Volunteers

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 |
| --- | --- |
| Active Comparator: Healthy: Dalfampridine-ER 7.5 mg<br>Dalfampridine-ER 7.5 mg single and steady-state dosing in healthy volunteers | Drug: Dalfampridine-ER<br>* 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up<br>|
| Active Comparator: Mild renal: Dalfampridine-ER 7.5 mg<br>Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with mild renal impairment | Drug: Dalfampridine-ER<br>* 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up<br>|
| Active Comparator: Moderate renal: Dalfampridine-ER 7.5 mg<br>Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with moderate renal impairment | Drug: Dalfampridine-ER<br>* 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). | AUC(0-12) was based on blood samples taken at specified outcome measure time frame for dalfampridine-ER 7.5 mg tablets in healthy adult volunteers and people with mild or moderate renal impairment. | 0 and 1,2,3,4,5,6,8, and 12 hours after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. |  | 7 days | 
| The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. |  | 7 days |