Characterization of the Effects of Prolonged-release Fampridine on Ambulatory Function in Patients With Multiple Sclerosis

NCT ID: NCT01576354

Last Updated: 2015-12-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2017-04-30

Brief Summary

The objective of the present investigator-initiated mono-center trial to be performed at the Department of Neurology of the University Hospital Zurich is a detailed characterization of the effects of prolonged-release fampridine on walking function of 50-70 patients with MS. In a randomized, double-blind, placebo-controlled study with cross-over design, changes of essential gait elements such as stability, coordination, correct loading, posture or endurance in addition to walking speed after treatment with prolonged-release fampridine will be investigated using a comprehensive kinematic gait analysis protocol. This protocol comprises outcome parameters ranging from very specific and sensitive biomechanical measures to clinically meaningful indicators of improved ambulatory function. Kinematic, kinetic and electromyographic gait parameters will be assessed during treadmill walking (primary outcome parameters). Changes in overground walking capacity will be investigated by means of different functional walking tests (e.g. six minute walk test). Furthermore, the patient's perception of the effects of the treatment on walking function will be evaluated by a standardized questionnaire. Changes of global ambulatory activity will be assessed (Actimeter) indicating a successful translation of improved gait (sub-)functions due to prolonged-release fampridine treatment into everyday life. The study will last for a period of 18 weeks, excluding the screening period. Based on the mechanism of action, the investigators hypothesize that treatment with prolonged-release fampridine will not only improve walking speed, but also clinically more meaningful features of walking function in patients with MS.

• Trial with medicinal product

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Prolonged-release Fampridine

Group Type: ACTIVE_COMPARATOR

Prolonged-release Fampridine

Intervention Type: DRUG

10mg tablet twice a day (every 12 hours), orally

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

tablet twice a day (every 12 hours), orally (matched placebo is provided as oval-shaped, white to off-white, matrix tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide)

Interventions

Prolonged-release Fampridine

10mg tablet twice a day (every 12 hours), orally

Intervention Type: DRUG

Placebo

tablet twice a day (every 12 hours), orally (matched placebo is provided as oval-shaped, white to off-white, matrix tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide)

Intervention Type: DRUG

Other Intervention Names

4-aminopyridine, dalfampridine, ampyra, fampyra

Eligibility Criteria

Inclusion Criteria

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.

2. Male or female subjects must be 18 to 65 years old, inclusive, at the time of informed consent.

3. Must have a diagnosis of either primary progressive, secondary progressive, progressive remitting, or relapsing remitting MS as defined by the revised McDonald Committee criteria [Lublin et al. 1996; McDonald et al. 2001; Polman et al. 2005; Section 22.4, Appendix L] of at least 3 months duration.

4. Must be able to walk at least 50 meters (with or without a walking aid) at each individual 6minWT conducted pre-randomization.

5. Must have an impaired walking function demonstrated by a mild gait ataxia (Functional System (FS) score = 2 in the cerebellar system component of the EDSS) or a FS score of > 2 in the pyramidal system component of the EDSS based only on evaluation of the lower limbs (hip flexors, knee flexors, knee extensors, and ankle dorsiflexors)or a restricted ambulation (< 1h walking duration) at the Screening Visit.

6. Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.

7. Subjects must be able to understand the patient information sheet and comply with the requirements of the protocol.

Exclusion Criteria

• Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood.
• Any prior treatment with anti-epileptic medications specifically prescribed for the treatment of epilepsy.
• Onset of MS exacerbation within the 60 days prior to the Screening Visit.
• Use of mitoxantrone, cyclophosphamide, rituximab, alemtuzumab, daclizumab, cladribine or any other immune suppressant (except FTY720) or antibody (except natalizumab) within 3 months prior to the Screening Visit, or scheduled use during study participation.
• Pulsed steroid treatment within the 60 days prior to the Screening Visit, or at any time during the screening period.
• Women who are pregnant or breast feeding,
• Clinically significant concomitant disease states such as renal failure, (e.g., moderate or severe renal impairment), hepatic dysfunction (e.g., acute or chronic hepatitis), cardiovascular or pulmonary disease, malignant disease (tumor, neoplasia) etc.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Contraindications to the class of drugs under study, e.g. known allergy to pyridine-containing substances.
• Any prior treatment with fampridine (4-aminopyridine; 4 AP) or 3,4-diaminopyridine in any formulation.
• Patients with an acute urinary tract infection at the Screening Visit as indicated by symptoms like painful urination/dysuria, urinary frequency, urinary urgency, pollakiuria, suprapubic pain, flank pain, costovertebral angle tenderness or fever >38°C in combination with a clinically significant pathological finding in the urine analysis (e.g., positive for leukocytes) at the Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Linnebank, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Zurich, Division of Neurology

Locations

University Hospital Zurich, Division of Neurology

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

References

Zorner B, Hostettler P, Meyer C, Killeen T, Gut P, Linnebank M, Weller M, Straumann D, Filli L. Prognosis of walking function in multiple sclerosis supported by gait pattern analysis. Mult Scler Relat Disord. 2022 Jul;63:103802. doi: 10.1016/j.msard.2022.103802. Epub 2022 Apr 10.

Reference Type: DERIVED

PMID: 35487034 (View on PubMed)

Weller D, Filli L, Meyer C, Lorincz L, Linnebank M, Weller M, Curt A, Zorner B. Impaired speed-dependent modulation of the gait pattern in multiple sclerosis. J Neurol. 2020 Oct;267(10):2998-3007. doi: 10.1007/s00415-020-09965-3. Epub 2020 Jun 4.

Reference Type: DERIVED

PMID: 32500374 (View on PubMed)

Filli L, Werner J, Beyer G, Reuter K, Petersen JA, Weller M, Zorner B, Linnebank M. Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis. Eur J Neurol. 2019 Feb;26(2):281-289. doi: 10.1111/ene.13805. Epub 2018 Oct 7.

Reference Type: DERIVED

PMID: 30171655 (View on PubMed)

Filli L, Zorner B, Kapitza S, Reuter K, Lorincz L, Weller D, Sutter T, Killeen T, Gruber P, Petersen JA, Weller M, Linnebank M. Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis. Neurology. 2017 Feb 28;88(9):832-841. doi: 10.1212/WNL.0000000000003656. Epub 2017 Feb 1.

Reference Type: DERIVED

PMID: 28148629 (View on PubMed)

Zorner B, Filli L, Reuter K, Kapitza S, Lorincz L, Sutter T, Weller D, Farkas M, Easthope CS, Czaplinski A, Weller M, Linnebank M. Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern. Mult Scler. 2016 Oct;22(11):1463-1475. doi: 10.1177/1352458515622695. Epub 2016 Jan 13.

Reference Type: DERIVED

PMID: 26762672 (View on PubMed)

Other Identifiers

FAMPKIN

Identifier Type: -

Identifier Source: org_study_id