prolonged - release ( pr ) fampridine tablets ( known as sustained / modified - release fampridine in some countries and extended - release dalfampridine in the united states ) are approved for improving walking in ms based on results from two pivotal trials that demonstrated consistent improvements in walking speed on the timed 25-foot walk and on patients self - assessment of ambulatory disability on the 12-item ms walking scale ( msws-12 ) .
walking is a complex activity influenced by many variables , including impairments in balance , which are frequent among patients with ms and correlate with slower walking speed .
furthermore , balance impairment is a strong predictor for perceived difficulty in mobility in ms .
this highlights the need for studies that assess effects of pr - fampridine on balance .
pr - fampridine improved standing balance in a small ( n = 8) 14-week study ; however , randomised , placebo - controlled studies assessing the effect of pr - fampridine on balance have not previously been performed .
the timed up and go ( tug ) test and berg balance scale ( bbs ) measure mobility / balance and have demonstrated high reliability in patients with ms . the objective of mobile was to explore the effect of pr - fampridine on endpoints related to patients self - assessed walking disability and dynamic / static balance , assessed using the bbs and tug , as well as to subjective impression of well - being and patients impression of change in walking .
this trial was conducted in compliance with the declaration of helsinki , the international conference on harmonisation good clinical practice guidelines , the european union clinical trials directive and local regulatory requirements .
written informed consent was obtained from each patient before any evaluations were conducted for eligibility .
the trial is registered on clinicaltrials.gov ( identifier nct01597297 ) and the european union clinical trials register ( eudract number 2012 - 000368 - 90 ) . mobile was a randomised , double - blind , exploratory , multi - centre , placebo - controlled trial in patients with ms ( electronic supplementary materials , figure 1 ) .
eligible patients were randomised ( 1:1 ) to receive pr - fampridine 10 mg tablets or matching placebo twice daily every 12 hours for 24 weeks .
scheduled visits took place at screening , day 1 and weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 .
a post - dosing follow - up visit was conducted two weeks after the end of treatment .
randomisation was determined by a centralised system on day 1 of the trial and treatment assignments were made through an interactive web response system .
all patients and trial staff , including the principal investigator , were blinded to patient treatment assignments .
treatment kits were prepared centrally and labelled with unique numbers , which were used to maintain the blind when drug supplies were dispensed .
eligible patients were male or female , aged 1870 years with an expanded disability status scale score of 4.07.0 and diagnosis of primary - progressive ms , secondary - progressive ms , progressive - relapsing ms or relapsing - remitting ms per revised mcdonald criteria of 3 months duration .
key exclusion criteria included : treatment with 4-aminopyridine or 3,4-diaminopyridine in any formulation 30 days before screening ; known allergy to pyridine - containing substances ; any history of seizure , epilepsy or other convulsive disorder ; renal impairment ( creatinine clearance < 80 ml / min ) ; onset of ms exacerbation 60 days before screening ; and a body mass index 40 kg / m .
outcome measures were assessed at screening , day 1 and weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 ( on - treatment period ) and at the week 26 follow - up visit ( except where noted otherwise ) . because this was an exploratory study , there were no pre - specified primary / secondary endpoints and
walking ability was assessed using the msws-12 and the seven - item patient global impression of change ( pgic ) scale .
the msws-12 is a 12-item questionnaire that asks patients to rate limitations of their mobility owing to ms during the preceding two weeks on a five - point scale ( from 1 = not at all to 5 = extremely ) .
total score ranges from 160 and was transformed to a scale of 0100 ; reduced score indicates improvement in walking .
the pgic is a global assessment of the patient s impression of how the study drug affected their overall walking during the preceding seven days .
the pgic was assessed at weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 , and scored on a seven - point scale ( from 1 = very much worse to 7 = very much improved ) .
mobility and dynamic balance were assessed using the tug test , which measures the time / speed it takes for a patient to stand up from a seated position , walk three metres out , turn around and walk back and return to the seated position .
static and dynamic balance were measured using the bbs , which is comprised of 14 balance - related tasks scored from 0 ( unable to perform ) to 4 ( able to perform independently ) .
the bbs is the sum of scores across these tasks and ranges from 0 ( poor balance ) to 56 ( good balance ) .
the tug and bbs , which have demonstrated high reliability in patients with ms , were chosen to further assess the impact of pr - fampridine treatment on mobility , specifically on static and dynamic balance .
balance has not been previously evaluated with pr - fampridine treatment in a randomised , placebo - controlled trial but may impact patients walking ability and mobility .
the impact of ms on the patient and quality of life ( qol ) were assessed using the 29-item multiple sclerosis impact scale ( msis-29 ) physical subscale ( phys ) and the euroqol-5 dimensions 5-level ( eq-5d-5l ) .
the self - administered msis-29 questionnaire contains a 20-item phys and a nine - item psychological subscale . for a particular visit ,
the msis-29 phys score was calculated by summing the 20 items and transforming the score to a scale with a range of 0 ( no impact of ms ) to 100 ( extreme impact of ms ) . negative change on the msis-29 phys indicates improvement in physical health .
the eq-5d-5l is a generic instrument comprised of five questions and a visual analogue scale ( vas ) .
a utility score is derived from the five questions addressing mobility , self - care , usual activities , pain / discomfort and anxiety / depression , with responses / scores ranging from 1 ( no problem ) to 5 ( severe problem ) .
the vas score ranges from 0 ( worst imagined health state ) to 100 ( best imagined health state ) .
the eq-5d was assessed at day 1 and weeks 4 , 8 , 12 , 16 , 20 and 24 , and a positive change in both the utility and vas scores indicates an improvement in health state .
safety and tolerability were assessed by monitoring adverse events ( aes ) , serious aes ( saes ) and concomitant medications and by performing physical examination , vital sign measurements and 12-lead electrocardiograms .
a sample size of 120 patients ( 60 patients per group ) was chosen based on bootstrapping that sampled data from a previous study to create 1000 datasets of 60 patients each , and repeated for sample sizes of 70 and 80 patients .
for each sample , the proportion of patients with a six - point change or more in msws-12 score was calculated , and the percentage of samples that fell within an interval of the actual percentage in the study was calculated to explore whether increasing the sample size increased the precision . using the sample size of 60 patients for both treatment groups ,
84% of samples were within 8% of the true proportion and increasing the size did not appreciably increase precision .
the intent - to - treat population consisted of all patients who were randomised , received at least one dose of treatment and had at least one post - baseline assessment for a given parameter .
efficacy analyses were based on an intent - to - treat analysis with missing data imputed by the last observation carried forward method when at least one post - baseline value was available .
baseline values were not carried forward and were defined as the mean over the screening and baseline visits .
mean changes in each efficacy endpoint , except for the pgic , were calculated over 24 weeks using the last observation carried forward values to calculate the average . because the pgic was designed to assess change since the previous visit , week 2 was the only time point that was valid for between - group comparisons of treatment effect .
based on the distribution of changes from baseline across patients , all by - visit analyses were summarised using median change from baseline on the outcome .
mean changes from baseline on the msws-12 were categorised using the following thresholds : a less than one - point improvement / no change / worsening and then increasing thresholds of improvement from 1 point to 10 points in one - point increments .
mean percentage changes from baseline in tug speed were categorised using the following thresholds : 0% ( worsening / no change ) , > 0% ( any improvement ) and then increasing thresholds of improvement from 10% to 40% in 5% increments .
these categories were summarised as the number / percentage of patients meeting each threshold . in order to characterise magnitude of the observed treatment effect relative to variance in the outcome measures ,
post hoc statistical testing compared multiple thresholds of improvement between treatment groups for msws-12 and tug using a logistic regression adjusted for baseline . multiple msws-12 thresholds of change were examined based on ranges previously identified as clinically meaningful ( 46 points based on a 100-point scale ) over three months .
a post hoc analysis using the chi - square test compared the percentage of patients in each treatment group who reported any improvement in pgic after two weeks of treatment . to assess magnitude of treatment effect over time
, changes from baseline to each visit also were summarised for each efficacy endpoint , except for pgic . for missing data in msws-12 , a visit in which 50% of the component questions were answered but at least one question was missing
msws-12 score was considered missing for a visit in which 50% of the questions were unanswered . for the tug test ,
two trials of the tug were conducted at each visit and speed for any particular visit was calculated as the average for trials 1 and 2 . if either trial was missing , then speed from the completed trial was used . for the bbs ,
if at least two questions were missing at a visit , the score was set to missing . if two or fewer questions were missing , these were imputed using the respondent - specific mean score . for msis-29 phys ,
if a patient had missing data for < 10 of the 20 items , the mean of the non - missing items was used to impute the missing items .
for eq-5d-5l , no imputation was used for missing values for the five summary scores or for vas .
a summary utility index value was calculated for patients with non - missing data for each of the five questions at a visit .
the crosswalk method was used to map eq-5d-5l to the eq-5d 3-level united kingdom value set , because value sets for eq-5d-5l are still under development .
utility index value ranges from 0.594 ( worst health state ) to 1.000 ( best health state ) .
this trial was conducted in compliance with the declaration of helsinki , the international conference on harmonisation good clinical practice guidelines , the european union clinical trials directive and local regulatory requirements .
written informed consent was obtained from each patient before any evaluations were conducted for eligibility .
the trial is registered on clinicaltrials.gov ( identifier nct01597297 ) and the european union clinical trials register ( eudract number 2012 - 000368 - 90 ) .
mobile was a randomised , double - blind , exploratory , multi - centre , placebo - controlled trial in patients with ms ( electronic supplementary materials , figure 1 ) .
eligible patients were randomised ( 1:1 ) to receive pr - fampridine 10 mg tablets or matching placebo twice daily every 12 hours for 24 weeks .
scheduled visits took place at screening , day 1 and weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 .
a post - dosing follow - up visit was conducted two weeks after the end of treatment .
randomisation was determined by a centralised system on day 1 of the trial and treatment assignments were made through an interactive web response system .
all patients and trial staff , including the principal investigator , were blinded to patient treatment assignments .
treatment kits were prepared centrally and labelled with unique numbers , which were used to maintain the blind when drug supplies were dispensed .
eligible patients were male or female , aged 1870 years with an expanded disability status scale score of 4.07.0 and diagnosis of primary - progressive ms , secondary - progressive ms , progressive - relapsing ms or relapsing - remitting ms per revised mcdonald criteria of 3 months duration .
key exclusion criteria included : treatment with 4-aminopyridine or 3,4-diaminopyridine in any formulation 30 days before screening ; known allergy to pyridine - containing substances ; any history of seizure , epilepsy or other convulsive disorder ; renal impairment ( creatinine clearance < 80 ml / min ) ; onset of ms exacerbation 60 days before screening ; and a body mass index 40 kg / m .
outcome measures were assessed at screening , day 1 and weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 ( on - treatment period ) and at the week 26 follow - up visit ( except where noted otherwise ) . because this was an exploratory study , there were no pre - specified primary / secondary endpoints and
walking ability was assessed using the msws-12 and the seven - item patient global impression of change ( pgic ) scale .
the msws-12 is a 12-item questionnaire that asks patients to rate limitations of their mobility owing to ms during the preceding two weeks on a five - point scale ( from 1 = not at all to 5 = extremely ) .
total score ranges from 160 and was transformed to a scale of 0100 ; reduced score indicates improvement in walking .
the pgic is a global assessment of the patient s impression of how the study drug affected their overall walking during the preceding seven days .
the pgic was assessed at weeks 2 , 4 , 8 , 12 , 16 , 20 and 24 , and scored on a seven - point scale ( from 1 = very much worse to 7 = very much improved ) .
mobility and dynamic balance were assessed using the tug test , which measures the time / speed it takes for a patient to stand up from a seated position , walk three metres out , turn around and walk back and return to the seated position .
static and dynamic balance were measured using the bbs , which is comprised of 14 balance - related tasks scored from 0 ( unable to perform ) to 4 ( able to perform independently ) .
the bbs is the sum of scores across these tasks and ranges from 0 ( poor balance ) to 56 ( good balance ) .
the tug and bbs , which have demonstrated high reliability in patients with ms , were chosen to further assess the impact of pr - fampridine treatment on mobility , specifically on static and dynamic balance .
balance has not been previously evaluated with pr - fampridine treatment in a randomised , placebo - controlled trial but may impact patients walking ability and mobility .
the impact of ms on the patient and quality of life ( qol ) were assessed using the 29-item multiple sclerosis impact scale ( msis-29 ) physical subscale ( phys ) and the euroqol-5 dimensions 5-level ( eq-5d-5l ) .
the self - administered msis-29 questionnaire contains a 20-item phys and a nine - item psychological subscale . for a particular visit ,
the msis-29 phys score was calculated by summing the 20 items and transforming the score to a scale with a range of 0 ( no impact of ms ) to 100 ( extreme impact of ms ) .
negative change on the msis-29 phys indicates improvement in physical health . the eq-5d-5l is a generic instrument comprised of five questions and a visual analogue scale ( vas ) .
a utility score is derived from the five questions addressing mobility , self - care , usual activities , pain / discomfort and anxiety / depression , with responses / scores ranging from 1 ( no problem ) to 5 ( severe problem ) .
the vas score ranges from 0 ( worst imagined health state ) to 100 ( best imagined health state ) .
the eq-5d was assessed at day 1 and weeks 4 , 8 , 12 , 16 , 20 and 24 , and a positive change in both the utility and vas scores indicates an improvement in health state .
safety and tolerability were assessed by monitoring adverse events ( aes ) , serious aes ( saes ) and concomitant medications and by performing physical examination , vital sign measurements and 12-lead electrocardiograms .
a sample size of 120 patients ( 60 patients per group ) was chosen based on bootstrapping that sampled data from a previous study to create 1000 datasets of 60 patients each , and repeated for sample sizes of 70 and 80 patients .
for each sample , the proportion of patients with a six - point change or more in msws-12 score was calculated , and the percentage of samples that fell within an interval of the actual percentage in the study was calculated to explore whether increasing the sample size increased the precision . using the sample size of 60 patients for both treatment groups ,
84% of samples were within 8% of the true proportion and increasing the size did not appreciably increase precision .
the intent - to - treat population consisted of all patients who were randomised , received at least one dose of treatment and had at least one post - baseline assessment for a given parameter .
efficacy analyses were based on an intent - to - treat analysis with missing data imputed by the last observation carried forward method when at least one post - baseline value was available .
baseline values were not carried forward and were defined as the mean over the screening and baseline visits .
mean changes in each efficacy endpoint , except for the pgic , were calculated over 24 weeks using the last observation carried forward values to calculate the average . because the pgic was designed to assess change since the previous visit , week 2 was the only time point that was valid for between - group comparisons of treatment effect .
based on the distribution of changes from baseline across patients , all by - visit analyses were summarised using median change from baseline on the outcome .
mean changes from baseline on the msws-12 were categorised using the following thresholds : a less than one - point improvement / no change / worsening and then increasing thresholds of improvement from 1 point to 10 points in one - point increments .
mean percentage changes from baseline in tug speed were categorised using the following thresholds : 0% ( worsening / no change ) , > 0% ( any improvement ) and then increasing thresholds of improvement from 10% to 40% in 5% increments .
these categories were summarised as the number / percentage of patients meeting each threshold . in order to characterise magnitude of the observed treatment effect relative to variance in the outcome measures ,
post hoc statistical testing compared multiple thresholds of improvement between treatment groups for msws-12 and tug using a logistic regression adjusted for baseline .
multiple msws-12 thresholds of change were examined based on ranges previously identified as clinically meaningful ( 46 points based on a 100-point scale ) over three months . a post hoc analysis using the chi - square test compared the percentage of patients in each treatment group who reported any improvement in pgic after two weeks of treatment . to assess magnitude of treatment effect over time
, changes from baseline to each visit also were summarised for each efficacy endpoint , except for pgic . for missing data in msws-12 , a visit in which 50% of the component questions were answered but at least one question was missing , scores from unanswered questions were imputed using the respondent - specific mean score .
msws-12 score was considered missing for a visit in which 50% of the questions were unanswered . for the tug test
, two trials of the tug were conducted at each visit and speed for any particular visit was calculated as the average for trials 1 and 2 . if either trial was missing , then speed from the completed trial was used . for the bbs ,
if at least two questions were missing at a visit , the score was set to missing . if two or fewer questions were missing , these were imputed using the respondent - specific mean score . for msis-29 phys ,
if a patient had missing data for < 10 of the 20 items , the mean of the non - missing items was used to impute the missing items .
for eq-5d-5l , no imputation was used for missing values for the five summary scores or for vas .
a summary utility index value was calculated for patients with non - missing data for each of the five questions at a visit .
the crosswalk method was used to map eq-5d-5l to the eq-5d 3-level united kingdom value set , because value sets for eq-5d-5l are still under development .
utility index value ranges from 0.594 ( worst health state ) to 1.000 ( best health state ) .
a total of 132 patients were randomised at 24 sites in belgium , canada , italy , the netherlands , sweden and the united kingdom .
the first patient was treated on 30 august 2012 and the trial ended on 8 august 2013 .
all randomised patients were treated and included in the analysis : 64 were treated with placebo and 68 with pr - fampridine . in each group ,
81% of patients completed treatment and 19% of patients discontinued treatment ( figure 1 ) .
ae was the most common reason for discontinuation and one patient in each treatment group discontinued owing to lack of efficacy ( figure 1 ) .
ae : adverse event ; crcl : creatinine clearance ; itt : intent - to - treat ; pr : prolonged - release .
bbs : berg balance scale ; edss : expanded disability status scale ; eq-5d-5l : euroqol-5 dimension 5-level ; msis-29 : 29-item multiple sclerosis impact scale ; msws-12 : 12-item multiple sclerosis walking scale ; nd : not determined ; phys : physical subscale ; ppms : primary - progressive multiple sclerosis ; pr : prolonged - release ; prms : progressive - relapsing multiple sclerosis ; rrms : relapsing - remitting multiple sclerosis ; spms : secondary - progressive multiple sclerosis ; tug : timed up and go ; vas : visual analogue scale .
pr - fampridine therapy resulted in greater median improvements from baseline in tug speed , bbs total score and msws-12 score compared with placebo during the 24-week treatment period ( figure 2(a ) , ( c ) and ( d ) ) .
after treatment discontinuation at week 24 , improvements declined and approached zero by the week 26 follow - up visit in the pr - fampridine group .
median changes from baseline and corresponding 95% confidence intervals in efficacy measures by study visit .
outcome measures : ( a ) 12-item multiple sclerosis walking scale ( msws-12 ) ; ( b ) 29-item multiple sclerosis impact scale ( msis-29 ) physical subscale ( phys ) ; ( c ) timed up and go ( tug ) test ; and ( d ) berg balance scale ( bbs ) were assessed at baseline ( mean over screening and day 1 ) and weeks 2 , 4 , 8 , 12 , 16 , 20 , 24 and week 26 ( off - treatment visit ; not assessed for msis-29 ) . error bars denote non - parametric 95% confidence interval for the median change at each visit .
when changes from baseline were summarised as a change at pre - specified thresholds of improvement , a higher proportion of patients receiving pr - fampridine versus placebo met each threshold of improvement in the tug test ( > 0% and from 10% to 40% ) , with statistically significant differences at thresholds 10% ( p = 0.0021 ) and 15% ( p = 0.0262 ; figure 3 ) .
similar results were observed for the msws-12 ; a higher proportion of patients receiving pr - fampridine versus placebo met each threshold of improvement in msws-12 ( 1 to 10 points ) with statistically significant differences at thresholds 7 ( p = 0.0275 ) , 8 ( p = 0.0153 ) and 9 ( p = 0.0088 ; figure 3 ) .
cumulative percentage of patients with mean improvement in 12-item multiple sclerosis walking scale ( msws-12 ) and timed up and go ( tug ) speed over 24 weeks .
msws-12 ( upper panel ) : cumulative percentage of patients with increasing levels of improvement on the msws-12 over the on - treatment period ( weeks 224 ) across multiple thresholds ( thresholds 1 to 10 represent improvements in 1 to 10 points ) .
tug speed ( lower panel ) : cumulative percentage of patients with average percent increase from baseline in tug speed over the on - treatment period ( weeks 224 ) across multiple thresholds .
pr - fampridine versus placebo : * p = 0.0275 ; * * p = 0.0153 ; * * * p = 0.0088 ; * * * * p = 0.0021 ; * * * * * p = 0.0262 .
hoc analysis , a significantly greater proportion of patients ( n ( % ) ) treated with pr - fampridine ( 31 ( 46% ) ) versus placebo ( 16 ( 26% ) ) also reported improvement on pgic at the week 2 visit ( p = 0.023 ) .
pr - fampridine therapy also resulted in greater improvements from baseline in msis-29 phys score versus placebo ( figure 2(b ) ) .
however , no apparent differences between treatment groups were observed in eq-5d-5l results ; median treatment difference ( 95% confidence interval ) for pr - fampridine versus placebo for eq-5d-5l vas was 0.00 ( 4.17 , 4.67 ) and for utility index was 0.00 ( 0.04 , 0.04 ) .
the proportion of patients with any ae was similar in placebo - treated patients ( 49 ( 77% ) ) versus patients receiving pr - fampridine ( 51 ( 75% ) ) .
nasopharyngitis and urinary tract infections ( utis ) were the most frequently reported aes in patients treated with pr - fampridine and placebo , respectively ( table 2 ) .
incidence of falls was higher in patients receiving placebo versus pr - fampridine , whereas incidences of balance disorder , gait disturbance and dizziness were higher in patients receiving pr - fampridine .
a lower proportion of patients receiving pr - fampridine ( 3% ) versus placebo ( 8% ) reported saes . in the pr - fampridine group ,
saes were considered unrelated to treatment and included moderate ms relapse in one patient and moderate ms relapse and severe paraparaesis ( worsened ms symptoms ) in the second patient .
ae : adverse event ; pr : prolonged - release ; sae : serious adverse event .
in this trial , pr - fampridine therapy resulted in greater / sustained improvements in mobility / balance over the six - month trial duration compared with placebo as measured by the tug test and bbs .
benefits were seen as early as two weeks after treatment initiation and were maintained throughout the trial . upon discontinuation of pr - fampridine therapy , improvements in outcome measures reversed and approached pre - treatment levels within two weeks .
early benefits also were seen in walking ability measured by msws-12 , and although msws-12 score fluctuated between weeks 4 and 12 , it stabilised after week 16 and benefits were maintained to the end of the study in patients receiving pr - fampridine therapy .
in addition to greater median improvements in tug speed and msws-12 score , a higher cumulative proportion of patients receiving pr - fampridine versus placebo met each threshold of improvement in tug speed ( > 0% and 10% to 40% ) and msws-12 score ( 1 to 10 points ) , including thresholds in a range ( 4 to 6 points ) previously identified as clinically meaningful for msws-12 with different data sources .
the mobile study was the first randomised , placebo - controlled study that assessed the effect of pr - fampridine on dynamic and static balance .
walking is a complex activity and individual patients with ms may improve in one or more domains , such as speed and/or balance .
the findings of mobile suggested that the previous definition of pr - fampridine responder that was based on walking speed alone may be too narrowly defined and may not identify some patients who received treatment benefits associated with improved balance .
pr - fampridine therapy also demonstrated improvements on msis-29 phys , a patient - reported measure of the physical impact of ms , but no clear differences between treatment groups were observed in eq-5d-5l vas and utility index results over time .
the discrepancy observed in this trial between the msis-29 and eq-5d-5l may be related to the insensitivity of generic measures to assess ms - related changes in qol .
the msis-29 phys results in this trial supported those observed in the enable study , in which pr - fampridine therapy demonstrated significant / clinically meaningful improvements on qol / health state , measured by a broad range of ms - specific and generic patient - reported endpoints , over 48 weeks in > 600 patients who received pr - fampridine .
safety findings from mobile were consistent with the known safety profile of pr - fampridine , with the exception that incidence of utis was higher in placebo - treated patients compared with patients receiving pr - fampridine .
this is in contrast to that observed in the pivotal studies , in which incidence of utis was higher for the pr - fampridine group . in the current study , utis were confirmed by culture . in contrast , the pivotal trials did not require confirmation of utis , which may have resulted in an overestimation of the rate of utis .
no seizures were observed in mobile and although more patients receiving pr - fampridine reported balance disorders , gait disturbance and dizziness versus placebo , the incidence of falls was higher in the placebo group .
balance disorders , gait disturbance and dizziness are broad , non - specific aes , and increases in these events may not result in an increase in falls , as was the case in the mobile study .
furthermore , the improvement in tug and bbs could have manifested in fewer falls among the patients treated with pr - fampridine .
the findings of mobile confirm and expand findings of previous controlled studies with a longer treatment period , geographically different study population and broader range of objective and patient - reported measures of mobility and balance to assess different domains of walking .
mobile was exploratory in design and its findings require confirmation in a prospective trial that is underway .
nevertheless , the results of mobile support that pr - fampridine therapy provides significant and sustained improvements in walking characteristics beyond walking speed ; in particular , pr - fampridine therapy resulted in early and sustained benefits on measures of dynamic and static balance and mobility as well as patient - reported walking disability .
overall , these findings provided additional support for the potential of pr - fampridine to result in clinically meaningful improvements in walking quality / ambulatory function in patients with ms with walking disability .
 background : mobility impairment is a common disability in ms and negatively impacts patients lives.objective:evaluate the effect of prolonged - release ( pr ) fampridine ( extended - release dalfampridine in the united states ) on self - assessed walking disability , dynamic / static balance and safety in patients with ms.methods:mobile was a randomised , double - blind , exploratory , placebo - controlled trial . 
 patients with progressive / relapsing - remitting ms and expanded disability status scale score of 4.07.0 were treated with pr - fampridine or placebo twice daily for 24 weeks . 
 efficacy endpoints included change from baseline in the 12-item ms walking scale ( msws-12 ) , timed up and go ( tug ) test and berg balance scale ( bbs).results:132 patients were randomised at 24 sites in six countries . pr - fampridine therapy resulted in greater median improvements from baseline in msws-12 score , tug speed and bbs total score versus placebo over 24 weeks 
 . a higher proportion of patients receiving pr - fampridine versus placebo experienced significant improvements at msws-12 improvement thresholds 7 ( p = 0.0275 ) , 8 ( p = 0.0153 ) and 9 points ( p = 0.0088 ) and tug speed thresholds 10% ( p = 0.0021 ) and 15% ( p = 0.0262 ) . 
 pr - fampridine was well tolerated.conclusions:pr-fampridine therapy resulted in early and sustained improvements in broad measures of walking and balance over six months . 