Clinical trial NCT01328379: Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis
Official title: Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Two Doses of Oral Dalfampridine Extended Release Tablets (5 mg and 10 mg Twice Daily) in Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Acorda Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-04-04
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety and efficacy of a lower dose of dalfampridine extended release tablets compared to the currently approved dose in improving walking in Multiple Sclerosis (MS) patients.

Detailed description: The current study is designed as a prospective placebo-controlled trial to investigate the safety and efficacy of a lower dose of dalfampridine extended release tablets (5 mg twice daily) compared to the approved commercial dose of 10 mg twice daily in improving walking in MS patients during a four-week period of treatment.

Eligibility criteria: Inclusion Criteria:

* Patient has clinically definite Multiple Sclerosis as defined by the MacDonald Criteria.
* Patient must be 18 to 70 years of age, inclusive (i.e. on or after their 18th birthday, up to the day before their 71st birthday at the Screening Visit).
* Patient who has previously taken Ampyra® or dalfampridine (fampridine or 4 aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn from the drug for at least one month prior to the Screening Visit.
* Patient must be mentally competent to understand and sign the Internal Review Board (IRB)-approved informed consent prior to the performance of any study-specific procedures.
* Patient is able to perform all the required study procedures.
* In the judgement of the Investigator, the patient has MS-related walking impairment but has sufficient ambulatory ability to be able to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening Visit and every study visit thereafter, with the two trials completed within 5 minutes of one another and in accordance with the specific instructions provided by the National Multiple Sclerosis Society MS Functional Composite Manual.
* Patient who is female and of childbearing potential (see Exclusion Criterion 1 for definition) must have a negative urine pregnancy test at the Screening Visit.

Exclusion Criteria:

* Patient is a female of childbearing potential (i.e., has not had a hysterectomy or bilateral oophorectomy, or is not at least two years postmenopausal), engaged in active heterosexual relations and is not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch or injectable contraceptive, double barrier method, or sexual activity restricted to vasectomized partner.
* Patient is pregnant or breastfeeding.
* Patient has any history of seizures.
* Patient has moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤ 50 mL/minute.
* Patient has active urinary tract infection (UTI) at Screening or within the 4 weeks before Screening.
* Patient has had an onset (as assessed by the treating physician) of an MS exacerbation within 60 days prior to the Screening Visit.
* Patient has started on a concomitant prescription medication regimen within the last three weeks, and/or their concomitant medication regimen is expected to change during the course of the study.
* Patient has received cyclophosphamide (Cytoxan) or mitoxantrone (Novantrone) for MS treatment within six months prior to the Screening Visit.
* Patient has started a treatment regimen of Betaseron, Avonex, Copaxone, Rebif, Tysabri, Extavia or Gilenya™ within 90 days prior to the Screening Visit or has had any change in the dosing regimen of these drugs within 30 days prior to the Screening Visit.
* Patient has received corticosteroids (other than topical preparations) within 30 days prior to the Screening Visit and/or is expected to receive regularly scheduled corticosteroid treatment during the course of the study.
* Patient has been administered botulinum toxin in the lower extremities within six months prior to the Screening Visit and/or is expected to receive botulinum toxin in the lower extremities during the course of the study.
* Patient has a known allergy to pyridine-containing substances or any of the inactive ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide).
* Patient has a history of drug or alcohol abuse within the past year.
* Patient has clinically significant abnormal laboratory values.
* Patient has angina, uncontrolled hypertension, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality.
* Patient has any medical condition (including psychiatric disease)that would interfere with the interpretation of the study results or the conduct of the study.
* Patient has participated in an investigational trial 30 days prior to Screening Visit or plans to enroll in another investigational trial at any time during this study. Non-drug (i.e. observational, registry) and non- medical device trials are allowed.

Primary outcomes:
measure: Change From Baseline in Walking Speed Near Maximum Plasma Concentration at Steady State (CmaxSS) of Placebo and Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
timeFrame: Baseline Visit 1 (double-blind study day 1) and approximately 3-4 hours post dose at Visit 3 (end of double-blind week 4)
Secondary outcomes:
measure: Change From Baseline in Walking Speed Near Minimum Plasma Concentration at Steady State (CminSS) of Placebo, Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
timeFrame: Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4)
measure: Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3
timeFrame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)
measure: Change From Baseline in MSWS-12 at Visit 2
timeFrame: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )
measure: Change From Baseline in Six-Minute Walk Distance at Visit 2
timeFrame: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )
measure: Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3.
timeFrame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)
measure: Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3.
timeFrame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates, PC
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Neurological Associates, Ltd
state: Arizona
city: Sun City
country: United States
facility: Arizona Neurological Institute
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage Inc.
state: Arizona
city: Berkeley
country: United States
facility: Sutter East Bay Physicians Medical Foundation
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center, Inc.
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Collaborative NeuroScience Network, Inc.
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Hartford
country: United States
facility: Mount Sinai Rehabilitation Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Maitland
country: United States
facility: Neurology Associates, PA
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine, Dept. of Neurology
state: Florida
city: Pompano Beach
country: United States
facility: Neurological Associates
state: Florida
city: Ponte Vedra
country: United States
facility: Neurologique Foundation, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc.
state: Florida
city: Sarasota
country: United States
facility: Negroski, Sutherland and Hanes Neurology
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic, PA
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Vero Beach
country: United States
facility: The Multiple Sclerosis Center of Vero Beach
state: Florida
city: Atlanta
country: United States
facility: Sheperd Center, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology Ltd.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, PC
state: Indiana
city: Des Moines
country: United States
facility: Methodist Plaza Specialty
state: Iowa
city: Des Moines
country: United States
facility: Ruan Neurology Clinic and Research Center
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Associates in Neurology, PSC
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland, Maryland Center for Multiple Sclerosis
state: Maryland
city: Lexington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Springfield
country: United States
facility: Springfield Neurology Associates, LLC
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Great Falls
country: United States
facility: Advanced Neurology Specialists
state: Montana
city: Reno
country: United States
facility: Veterans Administration Sierra Neveda Health Care System
state: Nevada
city: Albany
country: United States
facility: Upstate Clinical Research, LLC
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center MS Comprehensive Care Center
state: New York
city: Patchogue
country: United States
facility: Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates, PC
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte
state: North Carolina
city: Charlotte
country: United States
facility: The Neurological Institute, PA
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Grand Forks
country: United States
facility: Altru Health System Clinic
state: North Dakota
city: Bellevue
country: United States
facility: Northern Ohio Neuroscience, LLC
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Neurological Research Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Columbus
state: Ohio
city: Dayton
country: United States
facility: Neurology Specialists, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: OMRF Multiple Sclerosis Center of Excellence
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Providence Multiple Sclerosis Center
state: Oregon
city: Hershey
country: United States
facility: The Pennsylvania State University, Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Providence
country: United States
facility: The Neurology Foundation, Inc.
state: Rhode Island
city: Cordova
country: United States
facility: Wesley Neurology Clinic, PC
state: Tennessee
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Knoxville
country: United States
facility: Sibyl E. Wray, MD, Neurology, PC
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology, PA
state: Texas
city: Houston
country: United States
facility: Kelsey-Seybold Clinic
state: Texas
city: Houston
country: United States
facility: Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Newport News
country: United States
facility: Hampton Roads Neurology
state: Virginia
city: Richmond
country: United States
facility: Neurological Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Acorda Therapeutics
name: Andrew R. Blight, PhD
role: STUDY_DIRECTOR
affiliation: University of California, Davis
name: Mark Agius, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Vermont Medical Center
name: Angela Applebee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University Hospital
name: S. A Azizi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Francois Bethoux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, Maryland Center for Multiple Sclerosis
name: Christopher Bever, Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Metrolina Medical Research
name: Eric Borresen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University, Columbus
name: Aaron Boster, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lahey Clinic
name: Ann Camac, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Axiom Clinical Research of Florida
name: Mark Cascione, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: US Department of Veterans Affairs
name: Jane Chan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associates in Neurology, PSC
name: Warren Chumley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alta Bates Summit Medical Center
name: Joanna Cooper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Joy Derwenskus, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Suncoast Neuroscience Associates, Inc.
name: Adam DiDio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Advanced Neurology Specialists
name: Dennis Dietrich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurological Research Institute
name: Geoffery Eubank, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Raleigh Neurology Associates
name: Steven Freedman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loma Linda University Medical Center
name: Daniel Giang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology Specialists, Inc.
name: Lawrence Goldstick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Andrew Goodman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
name: Mark Gudesblatt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Phoenix Neurological Associates, LTD
name: Barry Hendin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Josephson Wallack Munshower Neurology, PC
name: Craig Herrman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology Associates, PA
name: William Honeycutt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruan Neurology Clinical Research Center
name: Bruce Hughes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Advanced Neurosciences Institute
name: Samuel Hunter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine
name: George Hutton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Dina Jacobs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Iowa Health Des Moines
name: Todd Janus, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Omar Khan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aurora Saint Luke's Medical Center
name: Bhupendra Khatri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charleston Area Medical Center Health Education and Research Institute, Inc.
name: Kiren Kresa-Reahl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Central Neurology Associates, PC
name: Christopher LaGanke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Kansas Medical Center
name: Sharon Lynch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Michele Mass, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: David Mattson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swedish Neuroscience Institute
name: Angeli Mayadev, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Negroski, Stein, Sutherland and Hanes Neurology
name: Donald Negroski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Island Neurological Associates, PC
name: Stephen Newman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mercy Multiple Sclerosis Center of Oklahoma Mercy Neuroscience Institute
name: Gabriel Pardo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Neurology, PA
name: C. Fish Greenfield, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology Clinic, PC
name: Rekha Pillai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Neurological Institute, PA
name: T. Hemanth Rao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rhode Island Hospital
name: Syed Rizvi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Altru Health System Research Center
name: Matthew Roller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Springfield Neurology Associates, LLC
name: Michael Rossen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurological Associates
name: Alan Schulman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Multiple Sclerosis Center of Vero Beach
name: James S Shafer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arizona Neurological Institute
name: Jatin Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami School of Medicine, Dept. of Neurology
name: William Sheremata, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurological Associates
name: Brian Steingo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Upstate Clinical Research, LLC
name: James Storey, Jr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shepherd Center, Inc.
name: Ben Thrower, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Georgetown University Hospital
name: Carlo Tornatore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hampton Roads Neurology
name: K A Lloyd, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Pennsylvania State University, Milton S. Hershey Medical Center
name: Anthony Turel, Jr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sibyl E. Wray, MD, Neurology, PC
name: Sibyl E Wray, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Consultants in Neurology Ltd.
name: Daniel Wynn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unifour Medical Research, LLC
name: Robert Yapundich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Applebee A, Goodman AD, Mayadev AS, Bethoux F, Goldman MD, Klingler M, Blight AR, Carrazana EJ. Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo-controlled Trial. Clin Ther. 2015 Dec 1;37(12):2780-7. doi: 10.1016/j.clinthera.2015.10.014. Epub 2015 Nov 10.
citation: Kantor D, Chancellor MB, Snell CW, Henney HR 3rd, Rabinowicz AL. Assessment of confirmed urinary tract infection in patients treated with dalfampridine for multiple sclerosis. Postgrad Med. 2015 Mar;127(2):218-22. doi: 10.1080/00325481.2015.1000229. Epub 2015 Jan 6.