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

• ClinicalTrials.gov Identifier: NCT01316055
• Recruitment Status: Completed
• First Posted: March 16, 2011
• Results First Posted: November 7, 2012
• Last Update Posted: November 7, 2012
• Sponsor: Acorda Therapeutics
• Information provided by (Responsible Party): Acorda Therapeutics

Tracking Information

• First Submitted Date: March 14, 2011
• First Posted Date: March 16, 2011
• Results First Submitted Date: August 24, 2012
• Results First Posted Date: November 7, 2012
• Last Update Posted Date: November 7, 2012
• Study Start Date: January 2011
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2012)

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 ]

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.

Original Primary Outcome Measures (submitted: March 15, 2011)

To characterize the steady-state pharmacokinetics of Dalfampridine-ER 7.5 mg tablets in healthy adults and people with mild and moderate renal impairment and to examine between group differences [ Time Frame: 7 days ]

pharmacokinetics of 7.5 mg dalfampridine-ER

Current Secondary Outcome Measures (submitted: October 9, 2012)

• 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 ]
• 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 ]

• Original Secondary Outcome Measures (submitted: March 15, 2011): To characterize the single dose pharmacokinetics 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 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetics (PK) of Dalfampridine-ER 7.5 mg BID in Healthy Volunteers and Subjects With Mild or Moderate Renal Impairment
• 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
• Brief Summary: 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: Pharmacokinetics in normal, mildly renally impaired, and moderately renally impaired subjects
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Renal Insufficiency

Intervention

Drug: Dalfampridine-ER

2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up

Study Arms

• Active Comparator: Healthy: Dalfampridine-ER 7.5 mg
  Dalfampridine-ER 7.5 mg single and steady-state dosing in healthy volunteers
  Intervention: Drug: Dalfampridine-ER
• 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
  Intervention: Drug: Dalfampridine-ER
• 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
  Intervention: Drug: Dalfampridine-ER

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 2, 2011): 42
• Original Estimated Enrollment (submitted: March 15, 2011): 36
• Actual Study Completion Date: September 2011
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01316055
• Other Study ID Numbers: RD7.5D-ER012010
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Acorda Therapeutics
• Original Responsible Party: Herbert R. Henney III, PharmD/ VP Medical Affairs, Acorda Therapeutics, Inc.
• Current Study Sponsor: Acorda Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Herbert R Henney, PharmD; Acorda Therapeutics

• PRS Account: Acorda Therapeutics
• Verification Date: October 2012