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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: Dalfampridine-ER

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • ACRI - Phase 1
  • Florida
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Healthy: Dalfampridine-ER 7.5 mg; Dalfampridine-ER 7.5 mg single and steady-state dosing in healthy volunteers	Drug: Dalfampridine-ER; 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up
ACTIVE_COMPARATOR: Mild renal: Dalfampridine-ER 7.5 mg; Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with mild renal impairment	Drug: Dalfampridine-ER; 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up
ACTIVE_COMPARATOR: Moderate renal: Dalfampridine-ER 7.5 mg; Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with moderate renal impairment	Drug: Dalfampridine-ER; 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Acorda Therapeutics
• Investigators: Study Director: Herbert R Henney, PharmD, Acorda Therapeutics

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (ESTIMATE): March 16, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 7, 2012
• Last Update Submitted That Met QC Criteria: October 9, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: RD7.5D-ER012010