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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Acorda Therapeutics
ClinicalTrials.gov Identifier:
NCT01316055
First received: March 14, 2011
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Renal Insufficiency
Drug: Dalfampridine-ER
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Acorda Therapeutics:

Primary Outcome Measures:
  • The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). [ Time Frame: 0 and 1,2,3,4,5,6,8, and 12 hours after the last dose ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: January 2011
Study Completion Date: September 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316055

Locations
United States, California
ACRI - Phase 1
Anaheim, California, United States, 92801
United States, Florida
MRA Clinical Research
South Miami, Florida, United States, 33143
Sponsors and Collaborators
Acorda Therapeutics
Investigators
Study Director: Herbert R Henney, PharmD Acorda Therapeutics
  More Information

No publications provided

Responsible Party: Acorda Therapeutics
ClinicalTrials.gov Identifier: NCT01316055     History of Changes
Other Study ID Numbers: RD7.5D-ER012010
Study First Received: March 14, 2011
Results First Received: August 24, 2012
Last Updated: October 9, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014