Page last updated: 2024-11-04

4-aminopyridine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

4-aminopyridine (4-AP) is a small organic molecule that acts as a potassium channel blocker. It was first synthesized in the early 20th century and has been studied extensively for its pharmacological properties. 4-AP is known to enhance neurotransmission by blocking potassium channels, which leads to prolonged action potentials and increased synaptic transmission. It has been shown to improve muscle function in patients with myasthenia gravis, a neuromuscular disorder. 4-AP is also being investigated for its potential therapeutic effects in other neurological conditions, such as epilepsy and Alzheimer's disease. However, 4-AP can also have side effects, including seizures and cardiovascular problems, and its use is therefore carefully monitored. The mechanism of action of 4-AP, its ability to enhance neurotransmission, and its potential therapeutic applications in neurological disorders make it a significant compound for ongoing research.'

Cross-References

ID SourceID
PubMed CID1727
CHEMBL ID284348
CHEBI ID34385
MeSH IDM0024148

Synonyms (244)

Synonym
HMS3267E21
gtpl2416
smr000058211
MLS000069400 ,
DIVK1C_000572
KBIO1_000572
ampydin
biib-041
dalfampridine-er
fampyra
fampridine-sr
SDCCGMLS-0066228.P001
fampridine-pr
neurelan
pymadin
el-970
amaya
pyridin-4-ylamine
AC-907/25014071
EU-0100032
SPECTRUM_000155
LOPAC0_000032
vmi-103
pymadine
caswell no. 038
ai3-52547
c5h6n2
hsdb 6037
epa pesticide chemical code 069201
einecs 207-987-9
brn 0105782
mi-w-3
rcra waste no. p008
nsc 15041
nsc15041
vmi-10-3
p-aminopyridine
wln: t6nj dz
pimadin (free base)
4-pyridylamine
amino-4 pyridine
4-ap
4-aminopyridine ,
4-pyridinamine
.gamma.-aminopyridine
prc 1237
vmi 10-3
nsc-15041
phillips 1861
compound 1861
avitrol
4 ap
avitrol 200
pyridine, 4-amino-
504-24-5
[j.pharmacol.exp.ther. 275:864 (1995)]
BIO1_001331
NCGC00015009-01
BIO1_000842
BIO1_000353
BIO2_000762
lopac-a-0152
BIO2_000282
tocris-0940
NCGC00024890-01
CHEBI:34385 ,
fampridine
ampyra
fampridina
gamma-aminopyridine
dalfampridine
fampridinum
n07xx07
philips 1861
fampridine (jan/inn)
ampyra (tn)
D04127
dalfampridine (usan)
fampyra (tn)
neurelan (tn)
IDI1_000572
IDI1_034032
pyridin-4-amine
pyridine,4-amino
inchi=1/c5h6n2/c6-5-1-3-7-4-2-5/h1-4h,(h2,6,7
UPCMLD-DP125:001
STK298717
4-aminopyridine, 98%
4-aminopyridine 10
chembl284348 ,
UPCMLD-DP125
bdbm10458
BSPBIO_001562
4-aminopyridine, >=99%
NCGC00024890-09
NCGC00024890-08
NCGC00024890-07
NCGC00024890-04
NCGC00024890-05
NCGC00024890-03
KBIOSS_000282
KBIO2_005771
KBIO2_000635
KBIO2_002850
KBIO3_001888
KBIO3_000564
KBIO3_000563
KBIO2_005418
KBIO2_003203
KBIOSS_000635
KBIOGR_000282
KBIO2_000282
KBIOGR_001505
SPECTRUM4_001013
SPECTRUM3_000914
SPECTRUM2_001413
NINDS_000572
SPBIO_001486
SPECTRUM1501130
SPECTRUM5_001501
NCGC00024890-10
NCGC00024890-02
NCGC00024890-06
4 aminopyridine
vmi 103
NCGC00015009-03
HMS2092F05
A 0152
HMS1989O04
A0414
NCGC00015009-12
fampridine (4-aminopyridine)
HMS1361O04
HMS501M14
HMS1791O04
FT-0665455
HMS1921H15
NCGC00015009-08
AKOS000119896
HMS3260G05
pyridin-4-yl-amine
tox21_200793
NCGC00258347-01
pharmakon1600-01501130
nsc-757845
nsc757845
dtxsid0023870 ,
cas-504-24-5
tox21_110065
dtxcid003870
HMS2234N24
4-amino pyridine
CCG-39031
NCGC00015009-05
NCGC00015009-13
NCGC00015009-06
NCGC00015009-02
NCGC00015009-14
NCGC00015009-04
NCGC00015009-10
NCGC00015009-07
NCGC00015009-09
NCGC00015009-11
cl-cob-iii-274-1
KUC111877N
biib041
dalfampridine [usan:inn]
fampridine [inn]
bh3b64okl9 ,
biib 041
unii-bh3b64okl9
5-22-09-00106 (beilstein handbook reference)
p-aminopyridine [un2671] [poison]
286367-79-1
4- aminopyridine
AM20061261
LP00032
fampridine [mart.]
fampridine [who-dd]
fampridine [vandf]
dalfampridine [usp-rs]
fampridine (4-aminopyridine) [vandf]
dalfampridine [ii]
fampridine [jan]
fampridine [ema epar]
dalfampridine [vandf]
dalfampridine [usan]
dalfampridine [mi]
dalfampridine [usp monograph]
dalfampridine [orange book]
dalfampridine [hsdb]
S5028
RB8003
4-aminopyrdine
HMS3370J03
BP-21343
DB06637
HY-B0604
tox21_110065_1
3RXF
NCGC00015009-16
tox21_500032
NCGC00260717-01
pyridine-4-ylamine
pyridine-4-amine
4-amino-pyridine
4-pyridyl amine
frampridine
Q-200436
methyl3,5-dibromo-2,4-dihydroxy-6-methylbenzoate
BS-3729
HMS3402O04
AB00052209_12
OPERA_ID_1768
mfcd00006439
F2190-0487
SR-01000075299-1
sr-01000075299
dalfampridine, united states pharmacopeia (usp) reference standard
4-aminopyridine, pestanal(r), analytical standard
SR-01000075299-3
SR-01000075299-5
SBI-0050021.P003
para-aminopyridine
HB1073
4-aminopyridine (4-ap)
Q372539
p-amino pyridine
HMS3678H13
acetyl-2-13c chloride,2,2-dichloro- (9ci)
HMS3414H15
1,4-dihydropyridin-4-imine
EN300-21310
SDCCGSBI-0050021.P004
HMS3886I09
NCGC00015009-24
NCGC00015009-23
dalfampridine (4-aminopyridine)
dalfampridine (ii)
usepa/opp pesticide code: 069201
fampridine (mart.)
dalfampridine (usp-rs)
dalfampridine (usp monograph)
Z104495272

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" 4-Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months."( Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial.
Brunnemann, SR; Charter, RS; Hernandez, JP; Himber, PL; Pathak, MS; Segal, JL, 1999
)
1.52
" We propose that T-kininogen may be required to counteract apoptosis in proximal tubular cells in order to minimize tissue damage following a toxic insult."( A correlation between a proteomic evaluation and conventional measurements in the assessment of renal proximal tubular toxicity.
Bandara, LR; Kelly, MD; Kennedy, S; Lock, EA, 2003
)
0.32
" Fourteen (56%) patients had 26 adverse reactions."( Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial.
Arenas-Hernández, R; Castañeda-Hernández, G; Grijalva, I; Guízar-Sahagún, G; Ibarra, A; Maldonado-Julián, H; Mino, D; Salgado-Ceballos, H; Serra, O; Vidal-Cantú, G, 2003
)
0.63
" Safety assessments: physical examinations, vital sign measurements, clinical laboratory tests, electrocardiogram recordings, and adverse events."( Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury.
Blight, AR; Cohen, R; Hayes, KC; Hsieh, JT; Katz, MA; Potter, PJ, 2004
)
0.56
" Adverse events were mild or moderate and were not dosage related."( Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury.
Blight, AR; Cohen, R; Hayes, KC; Hsieh, JT; Katz, MA; Potter, PJ, 2004
)
0.56
" Fampridine was well tolerated, with a higher frequency of adverse events at the supratherapeutic dose."( Assessment of the cardiac safety of fampridine-SR sustained-release tablets in a thorough QT/QTc evaluation at therapeutic and supratherapeutic doses in healthy individuals.
Cardi, T; March, B, 2009
)
0.35
"2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months."( 3,4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study.
Allain, H; Edan, G; Flet, L; Guillard, O; Javaudin, L; Leray, E; Polard, E, 2010
)
0.36
" At the therapeutic dose of 10 mg twice daily, adverse events were generally mild to moderate and, consistent with the mechanism of action of dalfampridine, were primarily related to stimulatory effects on the nervous system."( The safety profile of dalfampridine extended release in multiple sclerosis clinical trials.
Bienen, EJ; Blight, AR; Cornblath, DR, 2012
)
0.38
" There is a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported."( Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.
Capo, MA; Del Pino, J; Díaz, MJ; Frejo, MT; García, J; Lobo, M, 2014
)
0.68
" Otherwise, it has been described to produce a large number of adverse effects among them cell death mediated mainly by blockage of K(+) channels."( Neuroprotective or neurotoxic effects of 4-aminopyridine mediated by KChIP1 regulation through adjustment of Kv 4.3 potassium channels expression and GABA-mediated transmission in primary hippocampal cells.
Baselga, MJA; Capo, MA; Del Pino, J; Díaz, MJ; Frejo, MT; García, JM; Moyano, P, 2015
)
0.68
" Amifampridine phosphate was well tolerated; the most common adverse events were oral and digital paresthesias, nausea, and headache."( Amifampridine phosphate (Firdapse(®)) is effective and safe in a phase 3 clinical trial in LEMS.
Alsharabati, M; Blanco, JM; Brannagan, T; Dimachkie, M; Komoly, S; Kostera-Pruszczyk, A; Lavrnić, D; Meisel, A; Oh, SJ; Schoser, B; Shcherbakova, N; Shieh, PB; Sivakumar, K; So, Y; Vial, C, 2016
)
0.43
" It is also known that local anesthetics may exert analgesic effect and, rarely, some adverse effects on the central nervous system (CNS)."( Correlation between the increased release of catecholamines evoked by local anesthetics and their analgesic and adverse effects: Role of K(+) channel inhibition.
Azamfirei, L; Baranyi, M; Borbély, Z; Lazar, A; Sircuta, C; Vizi, ES, 2016
)
0.43
" Adverse events were consistent with previous D-ER trials, most commonly headache (13% D-ER, 4% placebo), fatigue (13% D-ER, 0% placebo), insomnia (8% D-ER, 4% placebo), diarrhea (4% D-ER, 4% placebo), and nausea (4% D-ER, 4% placebo)."( Safety, Tolerability, and Sensorimotor Effects of Extended-release Dalfampridine in Adults With Cerebral Palsy: A Pilot Study.
Bethoux, F; Blight, AR; Carrazana, E; Fatemi, A; Fowler, E; Marciniak, C; Mayadev, A; Rabinowicz, AL; Suarez, G; Waksman, J; Zackowski, K, 2017
)
0.46
"In this preliminary study of adults with CP, a BID dose of 10-mg D-ER was generally safe and well tolerated."( Safety, Tolerability, and Sensorimotor Effects of Extended-release Dalfampridine in Adults With Cerebral Palsy: A Pilot Study.
Bethoux, F; Blight, AR; Carrazana, E; Fatemi, A; Fowler, E; Marciniak, C; Mayadev, A; Rabinowicz, AL; Suarez, G; Waksman, J; Zackowski, K, 2017
)
0.46
" It was reviewed whether patients had suffered any of the most frequent adverse effects described in the pivotal clinical trial."( Assessment of the efficacy and safety of fampridine.
Castellano, P; Castro, C; López, LM; Mejuto, B, 2017
)
0.46
" Only one patient presented adverse effects."( Assessment of the efficacy and safety of fampridine.
Castellano, P; Castro, C; López, LM; Mejuto, B, 2017
)
0.46
" The tolerance is good, with mild to moderate, and transient adverse events."( Efficacy and safety of fampridine for walking disability in multiple sclerosis.
Arpín, EC, 2020
)
0.56
"The aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged ≥ 65 years and those with pre-existing cardiovascular risk factors)."( Safety, Patient-Reported Well-Being, and Physician-Reported Assessment of Walking Ability in Patients with Multiple Sclerosis for Prolonged-Release Fampridine Treatment in Routine Clinical Practice: Results of the LIBERATE Study.
Bergmann, A; Castelnovo, G; Castillo-Triviño, T; Freedman, MS; Gafson, AR; Gerlach, O; Killestein, J; Kong, G; Koster, T; Sinay, V; Williams, H, 2021
)
0.62
" Numeric dose response was seen for some secondary efficacy outcomes and adverse events."( A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment.
Cameron, MH; Cohen, JA; Elfont, R; Goldman, MD; Goodman, AD; Johnson, R; Llorens, L; Miller, AE; Patni, R; Rollins, A, 2022
)
0.72

Pharmacokinetics

ExcerptReferenceRelevance
" Plasma 4-aminopyridine hydrochloride vs time data best fit a 2-compartment pharmacokinetic model."( Pharmacokinetics of 4-aminopyridine in cattle.
Booth, NH; Bush, PB; Hendricks, HL; Kitzman, JV; Wilson, RC; Zahner, JM, 1984
)
1.03
" Serum data best fit a three-compartment pharmacokinetic model."( Pharmacokinetics and pharmacodynamics of 4-aminopyridine in anesthetized dogs.
Castagnoli, N; Fisher, DM; Miller, RD; Rupp, SM; Shinohara, Y, 1983
)
0.53
" The drug was rapidly absorbed with a tmax approximately 1 hour for both groups; tmax was independent of dose."( Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury.
Blight, AR; Devane, JG; Hayes, KC; Hsieh, JT; Katz, MA; Potter, PJ; Wolfe, DL, 2003
)
0.55
" Based on the pharmacokinetic profile of orally administered fampridine, multiple daily doses (4 or more) would need to be taken to sustain its therapeutic effects."( Pharmacokinetic studies of single and multiple oral doses of fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic spinal cord injury.
Blight, AR; Bugaresti, JM; Cohen, R; Hansebout, RR; Hayes, KC; Hsieh, JT; Katz, MA; Nicosia, S; Potter, PJ,
)
0.35
"Steady-state pharmacokinetic parameters: maximum observed plasma concentration (Cmax), minimum observed plasma concentration (Cmin), average observed plasma concentration (Cav), area under the plasma concentration-time curve from 0 to 12 hours (AUC(0-12)), time to Cmax (tmax), plasma half-life (t(1/2)), apparent volume of distribution (Vd/F), and apparent total clearance (Cl/F)."( Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury.
Blight, AR; Cohen, R; Hayes, KC; Hsieh, JT; Katz, MA; Potter, PJ, 2004
)
0.56
" Plasma pharmacokinetic parameters of the (14)C-radiolabeled drug were determined using standard liquid-scintillation techniques."( Pharmacokinetics of 14C-radioactivity after oral intake of a single dose of 14C-labeled fampridine (4-aminopyridine) in healthy volunteers.
Blight, AR; Henney, HR, 2009
)
0.57
" A sustained-release (SR) formulation of fampridine was developed to improve the agent's pharmacokinetic profile by extending its t((1/2)) relative to that of immediate-release fampridine."( Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial.
Henney, HR; Vollmer, T, 2009
)
0.35
" The pharmacokinetic parameters evaluated included C(max), T(max), AUC, elimination rate constant, apparent elimination t((1/2)), and apparent CL/F."( Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial.
Henney, HR; Vollmer, T, 2009
)
0.35
" Both sex and weight affected the pharmacokinetic parameters of fampridine SR."( Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial.
Henney, HR; Vollmer, T, 2009
)
0.35
"In these patients with MS, fampridine SR (5-20 mg) had a potentially advantageous pharmacokinetic profile relative to that associated with immediate-release fampridine and was generally well tolerated."( Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial.
Henney, HR; Vollmer, T, 2009
)
0.35
"The primary objective of this study, which followed on from the single-dose pharmacokinetic study, was to assess the steady-state pharmacokinetics of fampridine in patients with MS over 2 weeks of oral administration of open-label fampridine SR 20 mg BID."( Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.
Blight, AR; Henney, HR; Vollmer, T, 2009
)
0.35
" Fampridine pharmacokinetic parameters were determined on days 1, 8, and 15."( Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.
Blight, AR; Henney, HR; Vollmer, T, 2009
)
0.35
" Fampridine pharmacokinetic parameters on day 1 were consistent with those obtained in the single-dose study."( Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.
Blight, AR; Henney, HR; Vollmer, T, 2009
)
0.35
"In these patients with MS, the steady-state pharmacokinetic profile of fampridine SR 20 mg BID administered for 2 weeks appeared to support the use of twice-daily dosing in this population."( Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.
Blight, AR; Henney, HR; Vollmer, T, 2009
)
0.35
"Using data pooled from several studies of dalfampridine extended release (ER), a population pharmacokinetic model was developed for the purposes of characterizing the population pharmacokinetics and pharmacodynamics of dalfampridine-ER with respect to variability in pharmacokinetics, covariates affecting the pharmacokinetics, and whether the current therapeutic dosage represents an optimal dosage."( Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy volunteers and in patients with multiple sclerosis.
Gao, Y; Henney, HR; Weir, S, 2013
)
0.39
"9 hours) and apparent terminal plasma half-life (5."( Pharmacokinetic profile of dalfampridine extended release: clinical relevance in patients with multiple sclerosis.
Henney, HR; Torkin, R; Weir, S, 2013
)
0.39
" The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model."( Pharmacokinetics of 4-aminopyridine in horses.
Booth, NH; Bush, PB; Hendricks, HL; Kitzman, JV; Wilson, RC, 1984
)
0.59
" They were applied to a pharmacokinetic study in rats by a single oral dose."( Comparison of LC-UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: application to rat pharmacokinetic study.
Raja, RK; Suneetha, A, 2016
)
0.43
"The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes."( Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.
Datt, J; Haroldsen, PE; Ingenito, G; Musson, DG; Sisic, Z, 2017
)
0.46

Bioavailability

ExcerptReferenceRelevance
" The bioavailability of the enteric-coated tablets calculated from the area under the serum concentration curve (95 +/- 29%) did not differ from that calculated from urinary excretion (98 +/- 8%)."( 4-Aminopyridine kinetics.
Agoston, S; Greijdanus, B; Scaf, AH; Sohn, YJ; Uges, DR, 1982
)
1.71
" This scaffold evolved via medicinal chemistry to yield orally bioavailable leads with potent anti-T."( 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.
Calvet, CM; Cameron, MD; Choi, JY; Gut, J; Johnston, JB; Kellar, D; Khan, S; Lin, L; McKerrow, JH; Podust, LM; Roush, WR; Siqueira-Neto, JL; Vieira, DF, 2014
)
0.4
" This study assessed the effect of food on the relative bioavailability of amifampridine in healthy subjects and informed on conditions that can alter exposure."( Effects of Food Intake on the Relative Bioavailability of Amifampridine Phosphate Salt in Healthy Adults.
Hanson, B; Haroldsen, PE; Musson, DG; O'Neill, CA; Quartel, A, 2015
)
0.42
" The relative bioavailability values of amifampridine and metabolite were assessed based on the plasma PK parameters AUC0-∞, AUC0-t, and Cmax in the fed and fasted states using noncompartmental pharmacokinetic analysis."( Effects of Food Intake on the Relative Bioavailability of Amifampridine Phosphate Salt in Healthy Adults.
Hanson, B; Haroldsen, PE; Musson, DG; O'Neill, CA; Quartel, A, 2015
)
0.42
" Mouse oral bioavailability was complete (100%) with extensive tumor exposure."( The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.
Aherne, GW; Box, G; Boxall, KJ; Collins, I; De Haven Brandon, AK; Eccles, SA; Eve, PD; Garrett, MD; Hayes, A; Henley, AT; Hunter, JE; Lainchbury, M; Matthews, TP; McHardy, T; Osborne, J; Perkins, ND; Raynaud, FI; Reader, JC; Swales, K; Tall, M; Valenti, MR; Walton, MI, 2016
)
0.43
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
" Second, we tested the therapeutic effect of VP16 combined with CCT245737, an orally bioavailable CHK1 inhibitor, and observed strong synergistic anticancer effects in K562 cells."( Checkpoint kinase‑1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair.
Fan, Z; Lai, Q; Li, S; Liang, A; Luo, H; Wang, F; Wang, G; Wang, J; Xu, J; Xu, Y; Zhang, W; Zhou, J, 2020
)
0.56

Dosage Studied

4-aminopyridine (4-AP) (25-250 ng/mouse, i.e. ) produced a dose-dependent displacement to the right of the clonidine dose-response line. Decreasing K+ efflux using K+ channel blockers inhibited histamine release.

ExcerptRelevanceReference
" 3) Decreasing K+ efflux using K+ channel blockers (4-aminopyridine, quinine, sparteine) inhibited histamine release in a dose-response manner."( Regulation of human basophil activation. II. Histamine release is potentiated by K+ efflux and inhibited by Na+ influx.
Beauvais, F; Benveniste, J; Burtin, C; Hieblot, C; Inoue, I; Shimahara, T, 1992
)
0.53
" BMA caused "flattening" of the dose-response curves for 86Rb efflux induced by L-PIA, adenosine and carbachol with a significant reduction in response at the highest concentrations of adenosine and carbachol."( 86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria. Effects of potassium channel blockers.
Broadley, KJ; Rothaul, AL; Urquhart, RA, 1991
)
0.28
" When YOH was used as an anesthetic antagonist at dosage of 20 mg/kg, 20% mortality was observed and was attributable to acute respiratory arrest."( Antagonism of ketamine-xylazine anesthesia in rats by administration of yohimbine, tolazoline, or 4-aminopyridine.
Komulainen, A; Olson, ME, 1991
)
0.5
" Tissues from rats dosed with 4-aminopyridine were extracted with methylene chloride."( A high-performance liquid chromatography method for determination of 4-aminopyridine in tissues and urine.
Casteel, SW; Thomas, BR, 1990
)
0.8
" The patients were treated with oral 3,4-diaminopyridine, first with increasing single doses up to 100 mg and then with divided dosage for up to 3 weeks."( Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis.
Bever, CT; Camenga, DL; Johnson, KP; Leslie, J; Panitch, HS, 1990
)
0.28
" Rats were dosed daily for 20 d with soman (0."( Changes in nerve membrane polarization following repeated exposure to soman.
Anderson, RJ; Chamberlain, WL, 1988
)
0.27
" Using a dosage of 3-5 mg/kg there is a marked negative effect on the cardio-vascular system."( [The antagonism of ketamine/xylazine anesthesia ("Hellabrunn mixture") in wild zoo ruminants].
Erhardt, W; Hafner, S; Halm, S; von Hegel, G; Wiesner, H, 1989
)
0.28
" During thermal pain stimulation pymadine had the analgesic effect only at dosage of 5 mg/kg and potentiated the action of morphine given in doses of 3 and 5 mg/kg."( [Analgesic activity of pymadine].
Bantutova, I; Mitsov, V,
)
0.13
" The physostigmine dose-response curve for the stimulation of [3H]IP1 accumulation was similar to its dose-response curve to inhibit acetylcholinesterase activity in the neostriatum."( Physostigmine stimulates phosphoinositide breakdown in the rat neostriatum.
Aceves, J; Góngora, JL; Mariscal, S; Sierra, A, 1988
)
0.27
" According to published data and past experience, the dosage of xylazine used would be expected to provide 115, 120, and 100 minutes of immobilization in captive moose, mule deer, and white-tailed deer, respectively."( Use of yohimbine and 4-aminopyridine to antagonize xylazine-induced immobilization in North American Cervidae.
Olsen, CD; Renecker, LA, 1985
)
0.59
"Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0."( Antagonism of xylazine sedation by 4-aminopyridine and yohimbine in cattle.
Booth, NH; Hatch, RC; Kitzman, JV; Wallner, B, 1982
)
0.54
" The pooled mean dosage level of pentobarbital required for anesthesia was 12."( Meperidine-acepromazine-pentobarbital anesthesia in cats: reversal by 4-aminopyridine and yohimbine.
Booth, NH; Hatch, RC; Zahner, JM, 1984
)
0.5
"Groups of fasted atropinized crossbred dogs of both sexes were injected IM with a standard dosage of a xylazine-acepromazine combination (2."( Acepromazine-xylazine combination in dogs: antagonism with 4-aminopyridine and yohimbine.
Booth, NH; Brown, J; Cronin, MF; Hatch, RC, 1983
)
0.51
" Required dosage of pentobarbital, arousal and walk times (measured from injection of antagonists), respiratory rate, and heart rate were measured."( Comparison of five preanesthetic medicaments in pentobarbital-anesthetized dogs: antagonism by 4-aminopyridine, yohimbine, and naloxone.
Booth, NH; Clark, JD; Hatch, RC; Kitzman, JV, 1983
)
0.48
" Kinetic analysis of serum concentrations after intravenous dosing resulted in the best fitting of a triexponential model in five and a biexponential model in four subjects."( 4-Aminopyridine kinetics.
Agoston, S; Greijdanus, B; Scaf, AH; Sohn, YJ; Uges, DR, 1982
)
1.71
" We determined dosing to achieve the desired steady-state peak serum concentration ranges from a test dose and population pharmacokinetic parameters using bayesian estimation."( The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial.
Anderson, PA; Bever, CT; Conway, K; Dhib-Jalbut, S; Eddington, N; Krumholz, A; Leslie, J; Panitch, HS; Plaisance, KI; Young, D, 1994
)
0.64
" Dose-response relations for TEA and 4-AP were obtained by exposing single cells to ten concentrations exponentially distributed over four orders of magnitude."( Variations in the ensemble of potassium currents underlying resonance in turtle hair cells.
Art, JJ; Goodman, MB, 1996
)
0.29
" The dose-response curve for the inhibition of ISS by isoprenaline was positioned to the left of that for the calcium current."( Characterization of a beta-adrenergically inhibited K+ current in rat cardiac ventricular cells.
Scamps, F, 1996
)
0.29
" A bell-shaped dose-response relation was obtained for evoked [3H] overflow over the same concentration range, with maximum effects occurring at 10 microM for 4M2AP (163 +/- 31% increase) and 100 microM for 4AP (154 +/- 16% increase)."( Effects of 4-methyl-2-aminopyridine on [3H]-noradrenaline overflow and contractility of isolated rabbit arteries.
Fryer, MW; Glover, WE, 1997
)
0.3
" The dose-response characteristics of acutely and chronically injured axons were compared."( Conduction block in acute and chronic spinal cord injury: different dose-response characteristics for reversal by 4-aminopyridine.
Blight, AR; Kelly, TM; Shi, R, 1997
)
0.51
" Since the GLU receptors present at NMJ have been reported to be predominantly N-methyl-D-aspartate (NMDA) subtype, some non-competitive and competitive NMDA receptor blockers, MK801, ketamine, dextromethorphan and CGP 37849, and GLU release inhibitors, clonidine, guanfacine, tizanidine were used at their optimum concentrations in medium after having found them from dose-response curves."( N-methyl-D-aspartate antagonists, glutamate release inhibitors, 4-aminopyridine at neuromuscular transmission.
Günel, MA; Kara, I; Koyuncuoğlu, H; Nurten, A; Yamantürk, P, 1998
)
0.54
" A dose-response relationship was established for the K+ channel blockers."( Differential effects of potassium channel blockers on the activity of the locomotor network in neonatal rat.
Cazalets, JR; Magoul, R; Sqalli-Houssaini, Y, 1999
)
0.3
" In fact it showed: (1) very sensitive dose-response not affected by TTX in the bath; (2) an equilibrium potential compatible with Cl-channel conductance; (3) a massive reduction with the competitive GABA(A) antagonist bicuculline; (4) a small reduction, if any, with the potent competitive GABA(B) antagonist CGP55845A; (5) persistence of the responses under 4-AP (4-aminopyridine), the potassium channel blocker, and inhibition of the 4-AP-induced calcium bursts of spikes."( Purkinje cell inhibitory responses to 3-APPA (3-aminopropylphosphinic acid) in RAT cerebellar slices.
Batini, C; Vigot, R, 1999
)
0.47
" In isolated pulmonary arterial rings, 4-AP increased resting tension and caused a leftward shift in the KCl dose-response curve."( K(+) channel inhibition, calcium signaling, and vasomotor tone in canine pulmonary artery smooth muscle.
Damron, DS; Doi, S; Horibe, M; Murray, PA; Ogawa, K; Tanaka, S, 2000
)
0.31
"Following animal mode studies to establish dosing safety, six subjects with chronic SCI were examined."( Intrathecal administration of 4-aminopyridine in chronic spinal injured patients.
Blight, AR; Calvillo, O; Donovan, WH; Halter, JA, 2000
)
0.6
"Patients were randomized to receive either oral 4-AP 5 mg/day, which was increased by 5 mg/week to a maximum dosage of 30 mg/day, or placebo for 12 weeks."( Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial.
Arenas-Hernández, R; Castañeda-Hernández, G; Grijalva, I; Guízar-Sahagún, G; Ibarra, A; Maldonado-Julián, H; Mino, D; Salgado-Ceballos, H; Serra, O; Vidal-Cantú, G, 2003
)
0.63
"Mean steady-state Cmax, Cmin, Cav, and AUC(0-12) increased over the entire Fampridine-SR dosage range and were dosage dependent up to 50 mg twice daily."( Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury.
Blight, AR; Cohen, R; Hayes, KC; Hsieh, JT; Katz, MA; Potter, PJ, 2004
)
0.56
" With the use of a double sucrose gap-recording chamber we perform a dose-response assay to examine the effects of these compounds on axonal conduction following an in vitro stretch injury."( Dose responses of three 4-aminopyridine derivatives on axonal conduction in spinal cord trauma.
Borgens, RB; Byrn, SR; McBride, JM; Shi, R; Smith, DT, 2006
)
0.64
"In these patients with MS, the steady-state pharmacokinetic profile of fampridine SR 20 mg BID administered for 2 weeks appeared to support the use of twice-daily dosing in this population."( Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.
Blight, AR; Henney, HR; Vollmer, T, 2009
)
0.35
" Levcromakalim produced concentration-dependent inhibitory effect on myometrial spontaneity and relaxant effect and the dose-response curve (DRC) was shifted towards right in the presence of glybenclamaide."( Cellular coupling of potassium channels with beta2 adrenoceptors in mediating myometrial relaxation in buffaloes (Bubalus bubalis).
Choudhury, S; Garg, SK; Mishra, SK; Singh, TU, 2010
)
0.36
" The objective of this study was to evaluate the variability in dosage form weight, active content variability and impurity of compounded oral 3,4-DAP drug products."( Content variability of active drug substance in compounded oral 3,4-diaminopyridine products.
Brain, KR; Green, DM; Jones, AC, 2012
)
0.38
"Variability in dosage form weight ranged from 0·81% relative standard deviation (RSD) to 4·82% RSD."( Content variability of active drug substance in compounded oral 3,4-diaminopyridine products.
Brain, KR; Green, DM; Jones, AC, 2012
)
0.38
" This variability seems to be principally because of heterogeneous formulated material rather than variation in dosage form weight."( Content variability of active drug substance in compounded oral 3,4-diaminopyridine products.
Brain, KR; Green, DM; Jones, AC, 2012
)
0.38
"The study participants (n = 30) were randomly assigned to receive one 10-mg dalfampridine tablet in a fasted condition (no food for 10-12 hours) or a fed condition (after a high-fat meal); after a seven-day washout period, participants received the same dalfampridine dosage under the converse condition."( Effect of food on the single-dose pharmacokinetics and tolerability of dalfampridine extended-release tablets in healthy volunteers.
Blight, AR; Faust, B; Henney, HR, 2011
)
0.37
" The dosage of dalfampridine varied in clinical trials, but the recommended dosage is 10 mg orally twice daily."( Dalfampridine: a new agent for symptomatic management of multiple sclerosis.
Clements, JN; McDonald, S, 2011
)
0.37
"The literature searches returned 58 unique citations, of which 26 were considered relevant for characterizing the safety profile of dalfampridine; excluded citations were as follows: reviews (19), evaluation of 3,4-diaminopyridine (4), intravenous dosing (2), inadequate information on patient doses (2), preclinical models (2), and "other" (3)."( The safety profile of dalfampridine extended release in multiple sclerosis clinical trials.
Bienen, EJ; Blight, AR; Cornblath, DR, 2012
)
0.38
" Strict adherence to the prescribed dosing regimen is essential."( Clinical overview of the seizure risk of dalfampridine.
Bienen, EJ; Haut, SR; Miller, A, 2012
)
0.38
"Using data pooled from several studies of dalfampridine extended release (ER), a population pharmacokinetic model was developed for the purposes of characterizing the population pharmacokinetics and pharmacodynamics of dalfampridine-ER with respect to variability in pharmacokinetics, covariates affecting the pharmacokinetics, and whether the current therapeutic dosage represents an optimal dosage."( Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy volunteers and in patients with multiple sclerosis.
Gao, Y; Henney, HR; Weir, S, 2013
)
0.39
"The approved therapeutic dosage regimen of dalfampridine-ER 10 mg twice daily was identified as the optimum dosing regimen based on model-predicted exposure response relationships for efficacy and adverse events."( Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy volunteers and in patients with multiple sclerosis.
Gao, Y; Henney, HR; Weir, S, 2013
)
0.39
" With twice-daily dosing of dalfampridine-ER, time to peak plasma concentration (3."( Pharmacokinetic profile of dalfampridine extended release: clinical relevance in patients with multiple sclerosis.
Henney, HR; Torkin, R; Weir, S, 2013
)
0.39
"PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS."( A guide to treating gait impairment with prolonged-release fampridine (Fampyra
Álvarez-Cermeño, JC; Arroyo, R; Casanova-Estruch, B; Fernández, O; García-Merino, JA; Hernández, MA; Izquierdo, G; Martínez-Yélamos, S; Meca, J; Moral, E; Olascoaga, J; Prieto, JM; Ramió-Torrentà, L; Saiz, A, 2018
)
0.48
"Among the 24 total participants who were randomized to treatment and completed the twice daily dosing phase study, their mean age was 38."( Safety, Tolerability, and Sensorimotor Effects of Extended-release Dalfampridine in Adults With Cerebral Palsy: A Pilot Study.
Bethoux, F; Blight, AR; Carrazana, E; Fatemi, A; Fowler, E; Marciniak, C; Mayadev, A; Rabinowicz, AL; Suarez, G; Waksman, J; Zackowski, K, 2017
)
0.46
" Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI."( Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.
Datt, J; Haroldsen, PE; Ingenito, G; Musson, DG; Sisic, Z, 2017
)
0.46
" The daily dosage ranged from 36 to 100 mg."( [A retrospective study of the effects of 3,4-diaminopyridine treatment in Lambert-Eaton myasthenic syndrome].
Kano, T; Matsushima, M; Naganuma, R; Sasaki, H; Takahashi, I; Yabe, I, 2018
)
0.48
" The method proved to be applicable for active substance assay in a pharmaceutical dosage form."( HPLC method development for fampridine using Analytical Quality by Design approach.
Boda, F; Fülöp, I; Kelemen, ÉK; Kovács, B; Kovács-Deák, B; Székely-Szentmiklósi, B; Székely-Szentmiklósi, I, 2020
)
0.56
"5 mg D-ER, 10 mg D-ER, or placebo, dosed twice-daily for 12 weeks."( A double-blind, randomized, controlled study of two dose strengths of dalfampridine extended release on walking deficits in ischemic stroke.
Bockbrader, M; El-Feky, WH; Finklestein, SP; Goldstein, M; Kasner, SE; Ning, M; Page, SJ; Roberts, H; Wilson, CA, 2020
)
0.56
" We tested clinically relevant dosage of 4-AP as an acute treatment for experimental TBI and found multiple benefits in corpus callosum axons."( Acute axon damage and demyelination are mitigated by 4-aminopyridine (4-AP) therapy after experimental traumatic brain injury.
Armstrong, RC; Galdzicki, Z; Lischka, FW; Noble, MD; Radomski, KL; Zi, X, 2022
)
0.97
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
avicideA substance used to destroy bird pests (class Aves).
potassium channel blockerAn agent that inhibits cell membrane glycoproteins that are selectively permeable to potassium ions.
orphan drugAny drug that has been developed specifically for treatment of a rare medical condition, the condition itself being known as an orphan disease.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
aromatic amineAn amino compound in which the amino group is linked directly to an aromatic system.
aminopyridineCompounds containing a pyridine skeleton substituted by one or more amine groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (35)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency1,995.26000.003245.467312,589.2998AID2517
Chain A, CruzipainTrypanosoma cruziPotency3.35520.002014.677939.8107AID1476; AID1478
thioredoxin reductaseRattus norvegicus (Norway rat)Potency89.12510.100020.879379.4328AID588453; AID588456
RAR-related orphan receptor gammaMus musculus (house mouse)Potency0.61150.006038.004119,952.5996AID1159521
USP1 protein, partialHomo sapiens (human)Potency14.12540.031637.5844354.8130AID743255
Microtubule-associated protein tauHomo sapiens (human)Potency8.91250.180013.557439.8107AID1468
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency44.66840.011212.4002100.0000AID1030
thyroid stimulating hormone receptorHomo sapiens (human)Potency0.12590.001318.074339.8107AID926
estrogen receptor 2 (ER beta)Homo sapiens (human)Potency61.62820.000657.913322,387.1992AID1259377
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency34.67130.01237.983543.2770AID1645841
glucocorticoid receptor [Homo sapiens]Homo sapiens (human)Potency7.07950.000214.376460.0339AID588532
cytochrome P450 2D6Homo sapiens (human)Potency38.90180.00108.379861.1304AID1645840
glucocerebrosidaseHomo sapiens (human)Potency0.63100.01268.156944.6684AID2101
IDH1Homo sapiens (human)Potency29.09290.005210.865235.4813AID686970
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency0.02240.035520.977089.1251AID504332
nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105), isoform CRA_aHomo sapiens (human)Potency49.397919.739145.978464.9432AID1159509
cytochrome P450 2D6 isoform 1Homo sapiens (human)Potency0.06310.00207.533739.8107AID891
chromobox protein homolog 1Homo sapiens (human)Potency68.84290.006026.168889.1251AID488953; AID540317
transcriptional regulator ERG isoform 3Homo sapiens (human)Potency2.81840.794321.275750.1187AID624246
thyroid hormone receptor beta isoform 2Rattus norvegicus (Norway rat)Potency77.58540.000323.4451159.6830AID743065
mitogen-activated protein kinase 1Homo sapiens (human)Potency10.00000.039816.784239.8107AID1454
gemininHomo sapiens (human)Potency6.30960.004611.374133.4983AID624297
peripheral myelin protein 22Rattus norvegicus (Norway rat)Potency25.09990.005612.367736.1254AID624044
survival motor neuron protein isoform dHomo sapiens (human)Potency1.00000.125912.234435.4813AID1458
lethal factor (plasmid)Bacillus anthracis str. A2012Potency7.94330.020010.786931.6228AID912
lamin isoform A-delta10Homo sapiens (human)Potency0.89130.891312.067628.1838AID1487
Rap guanine nucleotide exchange factor 3Homo sapiens (human)Potency28.18386.309660.2008112.2020AID720707
Cellular tumor antigen p53Homo sapiens (human)Potency13.33320.002319.595674.0614AID651631
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency0.75690.060110.745337.9330AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
AcetylcholinesteraseRattus norvegicus (Norway rat)IC50 (µMol)500.00000.00020.52597.2000AID1796455
Pteridine reductase 1Leishmania majorIC50 (µMol)1,900.00002.95002.95002.9500AID554308
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)4,382.58010.00091.901410.0000AID240820; AID576612
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium channel subfamily K member 2Homo sapiens (human)EC50 (µMol)2,750.00000.18702.72248.1800AID1802150
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (193)

Processvia Protein(s)Taxonomy
cardiac ventricle developmentPotassium channel subfamily K member 2Homo sapiens (human)
G protein-coupled receptor signaling pathwayPotassium channel subfamily K member 2Homo sapiens (human)
memoryPotassium channel subfamily K member 2Homo sapiens (human)
response to mechanical stimulusPotassium channel subfamily K member 2Homo sapiens (human)
response to axon injuryPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of cardiac muscle cell proliferationPotassium channel subfamily K member 2Homo sapiens (human)
cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium channel subfamily K member 2Homo sapiens (human)
cochlea developmentPotassium channel subfamily K member 2Homo sapiens (human)
positive regulation of cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of DNA biosynthetic processPotassium channel subfamily K member 2Homo sapiens (human)
stabilization of membrane potentialPotassium channel subfamily K member 2Homo sapiens (human)
angiogenesisRap guanine nucleotide exchange factor 3Homo sapiens (human)
adaptive immune responseRap guanine nucleotide exchange factor 3Homo sapiens (human)
signal transductionRap guanine nucleotide exchange factor 3Homo sapiens (human)
adenylate cyclase-activating G protein-coupled receptor signaling pathwayRap guanine nucleotide exchange factor 3Homo sapiens (human)
associative learningRap guanine nucleotide exchange factor 3Homo sapiens (human)
Rap protein signal transductionRap guanine nucleotide exchange factor 3Homo sapiens (human)
regulation of actin cytoskeleton organizationRap guanine nucleotide exchange factor 3Homo sapiens (human)
negative regulation of syncytium formation by plasma membrane fusionRap guanine nucleotide exchange factor 3Homo sapiens (human)
intracellular signal transductionRap guanine nucleotide exchange factor 3Homo sapiens (human)
positive regulation of GTPase activityRap guanine nucleotide exchange factor 3Homo sapiens (human)
regulation of angiogenesisRap guanine nucleotide exchange factor 3Homo sapiens (human)
positive regulation of angiogenesisRap guanine nucleotide exchange factor 3Homo sapiens (human)
positive regulation of protein export from nucleusRap guanine nucleotide exchange factor 3Homo sapiens (human)
positive regulation of stress fiber assemblyRap guanine nucleotide exchange factor 3Homo sapiens (human)
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionRap guanine nucleotide exchange factor 3Homo sapiens (human)
positive regulation of syncytium formation by plasma membrane fusionRap guanine nucleotide exchange factor 3Homo sapiens (human)
establishment of endothelial barrierRap guanine nucleotide exchange factor 3Homo sapiens (human)
cellular response to cAMPRap guanine nucleotide exchange factor 3Homo sapiens (human)
Ras protein signal transductionRap guanine nucleotide exchange factor 3Homo sapiens (human)
regulation of insulin secretionRap guanine nucleotide exchange factor 3Homo sapiens (human)
negative regulation of cell population proliferationCellular tumor antigen p53Homo sapiens (human)
regulation of cell cycleCellular tumor antigen p53Homo sapiens (human)
regulation of cell cycle G2/M phase transitionCellular tumor antigen p53Homo sapiens (human)
DNA damage responseCellular tumor antigen p53Homo sapiens (human)
ER overload responseCellular tumor antigen p53Homo sapiens (human)
cellular response to glucose starvationCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
regulation of apoptotic processCellular tumor antigen p53Homo sapiens (human)
positive regulation of transcription by RNA polymerase IICellular tumor antigen p53Homo sapiens (human)
positive regulation of miRNA transcriptionCellular tumor antigen p53Homo sapiens (human)
negative regulation of transcription by RNA polymerase IICellular tumor antigen p53Homo sapiens (human)
mitophagyCellular tumor antigen p53Homo sapiens (human)
in utero embryonic developmentCellular tumor antigen p53Homo sapiens (human)
somitogenesisCellular tumor antigen p53Homo sapiens (human)
release of cytochrome c from mitochondriaCellular tumor antigen p53Homo sapiens (human)
hematopoietic progenitor cell differentiationCellular tumor antigen p53Homo sapiens (human)
T cell proliferation involved in immune responseCellular tumor antigen p53Homo sapiens (human)
B cell lineage commitmentCellular tumor antigen p53Homo sapiens (human)
T cell lineage commitmentCellular tumor antigen p53Homo sapiens (human)
response to ischemiaCellular tumor antigen p53Homo sapiens (human)
nucleotide-excision repairCellular tumor antigen p53Homo sapiens (human)
double-strand break repairCellular tumor antigen p53Homo sapiens (human)
regulation of DNA-templated transcriptionCellular tumor antigen p53Homo sapiens (human)
regulation of transcription by RNA polymerase IICellular tumor antigen p53Homo sapiens (human)
protein import into nucleusCellular tumor antigen p53Homo sapiens (human)
autophagyCellular tumor antigen p53Homo sapiens (human)
DNA damage responseCellular tumor antigen p53Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestCellular tumor antigen p53Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatorCellular tumor antigen p53Homo sapiens (human)
transforming growth factor beta receptor signaling pathwayCellular tumor antigen p53Homo sapiens (human)
Ras protein signal transductionCellular tumor antigen p53Homo sapiens (human)
gastrulationCellular tumor antigen p53Homo sapiens (human)
neuroblast proliferationCellular tumor antigen p53Homo sapiens (human)
negative regulation of neuroblast proliferationCellular tumor antigen p53Homo sapiens (human)
protein localizationCellular tumor antigen p53Homo sapiens (human)
negative regulation of DNA replicationCellular tumor antigen p53Homo sapiens (human)
negative regulation of cell population proliferationCellular tumor antigen p53Homo sapiens (human)
determination of adult lifespanCellular tumor antigen p53Homo sapiens (human)
mRNA transcriptionCellular tumor antigen p53Homo sapiens (human)
rRNA transcriptionCellular tumor antigen p53Homo sapiens (human)
response to salt stressCellular tumor antigen p53Homo sapiens (human)
response to inorganic substanceCellular tumor antigen p53Homo sapiens (human)
response to X-rayCellular tumor antigen p53Homo sapiens (human)
response to gamma radiationCellular tumor antigen p53Homo sapiens (human)
positive regulation of gene expressionCellular tumor antigen p53Homo sapiens (human)
cardiac muscle cell apoptotic processCellular tumor antigen p53Homo sapiens (human)
positive regulation of cardiac muscle cell apoptotic processCellular tumor antigen p53Homo sapiens (human)
glial cell proliferationCellular tumor antigen p53Homo sapiens (human)
viral processCellular tumor antigen p53Homo sapiens (human)
glucose catabolic process to lactate via pyruvateCellular tumor antigen p53Homo sapiens (human)
cerebellum developmentCellular tumor antigen p53Homo sapiens (human)
negative regulation of cell growthCellular tumor antigen p53Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
negative regulation of transforming growth factor beta receptor signaling pathwayCellular tumor antigen p53Homo sapiens (human)
mitotic G1 DNA damage checkpoint signalingCellular tumor antigen p53Homo sapiens (human)
negative regulation of telomere maintenance via telomeraseCellular tumor antigen p53Homo sapiens (human)
T cell differentiation in thymusCellular tumor antigen p53Homo sapiens (human)
tumor necrosis factor-mediated signaling pathwayCellular tumor antigen p53Homo sapiens (human)
regulation of tissue remodelingCellular tumor antigen p53Homo sapiens (human)
cellular response to UVCellular tumor antigen p53Homo sapiens (human)
multicellular organism growthCellular tumor antigen p53Homo sapiens (human)
positive regulation of mitochondrial membrane permeabilityCellular tumor antigen p53Homo sapiens (human)
cellular response to glucose starvationCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
positive regulation of apoptotic processCellular tumor antigen p53Homo sapiens (human)
negative regulation of apoptotic processCellular tumor antigen p53Homo sapiens (human)
entrainment of circadian clock by photoperiodCellular tumor antigen p53Homo sapiens (human)
mitochondrial DNA repairCellular tumor antigen p53Homo sapiens (human)
regulation of DNA damage response, signal transduction by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
positive regulation of neuron apoptotic processCellular tumor antigen p53Homo sapiens (human)
transcription initiation-coupled chromatin remodelingCellular tumor antigen p53Homo sapiens (human)
negative regulation of proteolysisCellular tumor antigen p53Homo sapiens (human)
negative regulation of DNA-templated transcriptionCellular tumor antigen p53Homo sapiens (human)
positive regulation of DNA-templated transcriptionCellular tumor antigen p53Homo sapiens (human)
positive regulation of RNA polymerase II transcription preinitiation complex assemblyCellular tumor antigen p53Homo sapiens (human)
positive regulation of transcription by RNA polymerase IICellular tumor antigen p53Homo sapiens (human)
response to antibioticCellular tumor antigen p53Homo sapiens (human)
fibroblast proliferationCellular tumor antigen p53Homo sapiens (human)
negative regulation of fibroblast proliferationCellular tumor antigen p53Homo sapiens (human)
circadian behaviorCellular tumor antigen p53Homo sapiens (human)
bone marrow developmentCellular tumor antigen p53Homo sapiens (human)
embryonic organ developmentCellular tumor antigen p53Homo sapiens (human)
positive regulation of peptidyl-tyrosine phosphorylationCellular tumor antigen p53Homo sapiens (human)
protein stabilizationCellular tumor antigen p53Homo sapiens (human)
negative regulation of helicase activityCellular tumor antigen p53Homo sapiens (human)
protein tetramerizationCellular tumor antigen p53Homo sapiens (human)
chromosome organizationCellular tumor antigen p53Homo sapiens (human)
neuron apoptotic processCellular tumor antigen p53Homo sapiens (human)
regulation of cell cycleCellular tumor antigen p53Homo sapiens (human)
hematopoietic stem cell differentiationCellular tumor antigen p53Homo sapiens (human)
negative regulation of glial cell proliferationCellular tumor antigen p53Homo sapiens (human)
type II interferon-mediated signaling pathwayCellular tumor antigen p53Homo sapiens (human)
cardiac septum morphogenesisCellular tumor antigen p53Homo sapiens (human)
positive regulation of programmed necrotic cell deathCellular tumor antigen p53Homo sapiens (human)
protein-containing complex assemblyCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressCellular tumor antigen p53Homo sapiens (human)
thymocyte apoptotic processCellular tumor antigen p53Homo sapiens (human)
positive regulation of thymocyte apoptotic processCellular tumor antigen p53Homo sapiens (human)
necroptotic processCellular tumor antigen p53Homo sapiens (human)
cellular response to hypoxiaCellular tumor antigen p53Homo sapiens (human)
cellular response to xenobiotic stimulusCellular tumor antigen p53Homo sapiens (human)
cellular response to ionizing radiationCellular tumor antigen p53Homo sapiens (human)
cellular response to gamma radiationCellular tumor antigen p53Homo sapiens (human)
cellular response to UV-CCellular tumor antigen p53Homo sapiens (human)
stem cell proliferationCellular tumor antigen p53Homo sapiens (human)
signal transduction by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathway by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
reactive oxygen species metabolic processCellular tumor antigen p53Homo sapiens (human)
cellular response to actinomycin DCellular tumor antigen p53Homo sapiens (human)
positive regulation of release of cytochrome c from mitochondriaCellular tumor antigen p53Homo sapiens (human)
cellular senescenceCellular tumor antigen p53Homo sapiens (human)
replicative senescenceCellular tumor antigen p53Homo sapiens (human)
oxidative stress-induced premature senescenceCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathwayCellular tumor antigen p53Homo sapiens (human)
oligodendrocyte apoptotic processCellular tumor antigen p53Homo sapiens (human)
positive regulation of execution phase of apoptosisCellular tumor antigen p53Homo sapiens (human)
negative regulation of mitophagyCellular tumor antigen p53Homo sapiens (human)
regulation of mitochondrial membrane permeability involved in apoptotic processCellular tumor antigen p53Homo sapiens (human)
regulation of intrinsic apoptotic signaling pathway by p53 class mediatorCellular tumor antigen p53Homo sapiens (human)
positive regulation of miRNA transcriptionCellular tumor antigen p53Homo sapiens (human)
negative regulation of G1 to G0 transitionCellular tumor antigen p53Homo sapiens (human)
negative regulation of miRNA processingCellular tumor antigen p53Homo sapiens (human)
negative regulation of glucose catabolic process to lactate via pyruvateCellular tumor antigen p53Homo sapiens (human)
negative regulation of pentose-phosphate shuntCellular tumor antigen p53Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to hypoxiaCellular tumor antigen p53Homo sapiens (human)
regulation of fibroblast apoptotic processCellular tumor antigen p53Homo sapiens (human)
negative regulation of reactive oxygen species metabolic processCellular tumor antigen p53Homo sapiens (human)
positive regulation of reactive oxygen species metabolic processCellular tumor antigen p53Homo sapiens (human)
negative regulation of stem cell proliferationCellular tumor antigen p53Homo sapiens (human)
positive regulation of cellular senescenceCellular tumor antigen p53Homo sapiens (human)
positive regulation of intrinsic apoptotic signaling pathwayCellular tumor antigen p53Homo sapiens (human)
potassium ion transportPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
optic nerve developmentPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
corpus callosum developmentPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
protein homooligomerizationPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
action potentialPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
startle responsePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
regulation of muscle contractionPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuroblast proliferationPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
protein localizationPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cell communication by electrical couplingPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
magnesium ion homeostasisPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuronal action potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
optic nerve developmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
hippocampus developmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cerebral cortex developmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
corpus callosum developmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuronal signal transductionPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuromuscular processPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
detection of mechanical stimulus involved in sensory perception of painPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
detection of mechanical stimulus involved in sensory perception of touchPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
protein homooligomerizationPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
regulation of postsynaptic membrane potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
axon developmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cellular response to magnesium ionPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
regulation of presynaptic membrane potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
action potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (50)

Processvia Protein(s)Taxonomy
outward rectifier potassium channel activityPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion leak channel activityPotassium channel subfamily K member 2Homo sapiens (human)
guanyl-nucleotide exchange factor activityRap guanine nucleotide exchange factor 3Homo sapiens (human)
protein bindingRap guanine nucleotide exchange factor 3Homo sapiens (human)
protein domain specific bindingRap guanine nucleotide exchange factor 3Homo sapiens (human)
cAMP bindingRap guanine nucleotide exchange factor 3Homo sapiens (human)
transcription cis-regulatory region bindingCellular tumor antigen p53Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingCellular tumor antigen p53Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificCellular tumor antigen p53Homo sapiens (human)
cis-regulatory region sequence-specific DNA bindingCellular tumor antigen p53Homo sapiens (human)
core promoter sequence-specific DNA bindingCellular tumor antigen p53Homo sapiens (human)
TFIID-class transcription factor complex bindingCellular tumor antigen p53Homo sapiens (human)
DNA-binding transcription repressor activity, RNA polymerase II-specificCellular tumor antigen p53Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificCellular tumor antigen p53Homo sapiens (human)
protease bindingCellular tumor antigen p53Homo sapiens (human)
p53 bindingCellular tumor antigen p53Homo sapiens (human)
DNA bindingCellular tumor antigen p53Homo sapiens (human)
chromatin bindingCellular tumor antigen p53Homo sapiens (human)
DNA-binding transcription factor activityCellular tumor antigen p53Homo sapiens (human)
mRNA 3'-UTR bindingCellular tumor antigen p53Homo sapiens (human)
copper ion bindingCellular tumor antigen p53Homo sapiens (human)
protein bindingCellular tumor antigen p53Homo sapiens (human)
zinc ion bindingCellular tumor antigen p53Homo sapiens (human)
enzyme bindingCellular tumor antigen p53Homo sapiens (human)
receptor tyrosine kinase bindingCellular tumor antigen p53Homo sapiens (human)
ubiquitin protein ligase bindingCellular tumor antigen p53Homo sapiens (human)
histone deacetylase regulator activityCellular tumor antigen p53Homo sapiens (human)
ATP-dependent DNA/DNA annealing activityCellular tumor antigen p53Homo sapiens (human)
identical protein bindingCellular tumor antigen p53Homo sapiens (human)
histone deacetylase bindingCellular tumor antigen p53Homo sapiens (human)
protein heterodimerization activityCellular tumor antigen p53Homo sapiens (human)
protein-folding chaperone bindingCellular tumor antigen p53Homo sapiens (human)
protein phosphatase 2A bindingCellular tumor antigen p53Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingCellular tumor antigen p53Homo sapiens (human)
14-3-3 protein bindingCellular tumor antigen p53Homo sapiens (human)
MDM2/MDM4 family protein bindingCellular tumor antigen p53Homo sapiens (human)
disordered domain specific bindingCellular tumor antigen p53Homo sapiens (human)
general transcription initiation factor bindingCellular tumor antigen p53Homo sapiens (human)
molecular function activator activityCellular tumor antigen p53Homo sapiens (human)
promoter-specific chromatin bindingCellular tumor antigen p53Homo sapiens (human)
voltage-gated monoatomic ion channel activityPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
outward rectifier potassium channel activityPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
disordered domain specific bindingPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potentialPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (51)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
cell surfacePotassium channel subfamily K member 2Homo sapiens (human)
apical plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
neuronal cell bodyPotassium channel subfamily K member 2Homo sapiens (human)
calyx of HeldPotassium channel subfamily K member 2Homo sapiens (human)
astrocyte projectionPotassium channel subfamily K member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membraneRap guanine nucleotide exchange factor 3Homo sapiens (human)
cortical actin cytoskeletonRap guanine nucleotide exchange factor 3Homo sapiens (human)
plasma membraneRap guanine nucleotide exchange factor 3Homo sapiens (human)
microvillusRap guanine nucleotide exchange factor 3Homo sapiens (human)
endomembrane systemRap guanine nucleotide exchange factor 3Homo sapiens (human)
membraneRap guanine nucleotide exchange factor 3Homo sapiens (human)
lamellipodiumRap guanine nucleotide exchange factor 3Homo sapiens (human)
filopodiumRap guanine nucleotide exchange factor 3Homo sapiens (human)
extracellular exosomeRap guanine nucleotide exchange factor 3Homo sapiens (human)
nuclear bodyCellular tumor antigen p53Homo sapiens (human)
nucleusCellular tumor antigen p53Homo sapiens (human)
nucleoplasmCellular tumor antigen p53Homo sapiens (human)
replication forkCellular tumor antigen p53Homo sapiens (human)
nucleolusCellular tumor antigen p53Homo sapiens (human)
cytoplasmCellular tumor antigen p53Homo sapiens (human)
mitochondrionCellular tumor antigen p53Homo sapiens (human)
mitochondrial matrixCellular tumor antigen p53Homo sapiens (human)
endoplasmic reticulumCellular tumor antigen p53Homo sapiens (human)
centrosomeCellular tumor antigen p53Homo sapiens (human)
cytosolCellular tumor antigen p53Homo sapiens (human)
nuclear matrixCellular tumor antigen p53Homo sapiens (human)
PML bodyCellular tumor antigen p53Homo sapiens (human)
transcription repressor complexCellular tumor antigen p53Homo sapiens (human)
site of double-strand breakCellular tumor antigen p53Homo sapiens (human)
germ cell nucleusCellular tumor antigen p53Homo sapiens (human)
chromatinCellular tumor antigen p53Homo sapiens (human)
transcription regulator complexCellular tumor antigen p53Homo sapiens (human)
protein-containing complexCellular tumor antigen p53Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
presynaptic membranePotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
calyx of HeldPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
membrane raftPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
postsynaptic membranePotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
glutamatergic synapsePotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
axonPotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
membranePotassium voltage-gated channel subfamily A member 3Homo sapiens (human)
endoplasmic reticulumPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cytosolPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
apical plasma membranePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cell junctionPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
dendritePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
cytoplasmic vesiclePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
paranode region of axonPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
presynaptic membranePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuronal cell bodyPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
axon initial segmentPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
perikaryonPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
axon terminusPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
juxtaparanode region of axonPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
calyx of HeldPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
synapsePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
postsynaptic membranePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
anchoring junctionPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
glutamatergic synapsePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
dendritePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
paranode region of axonPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
membranePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
synapsePotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
juxtaparanode region of axonPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
neuronal cell bodyPotassium voltage-gated channel subfamily A member 1Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (129)

Assay IDTitleYearJournalArticle
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID554316Inhibition of human DHFR at 500 uM2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase.
AID619509Dissociation constant, pKa of the compound in aqueous solution2011Journal of medicinal chemistry, Oct-13, Volume: 54, Issue:19
Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
AID32092Inhibition of acetylcholinesterase activity in rat cerebral cortex homogenate, in the presence of a specific butyrylcholinesterase (BChE) inhibitor; ethopropazine1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Heterodimeric tacrine-based acetylcholinesterase inhibitors: investigating ligand-peripheral site interactions.
AID1145387Partition coefficient, log P of the compound by HPLC analysis1976Journal of medicinal chemistry, May, Volume: 19, Issue:5
Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography.
AID313503Antiamnesic activity in scopolamine-induced memory deficit rat assessed as training trial latency time at 0.1 mg/kg, ip2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID313500Antiamnesic activity in scopolamine-induced memory deficit rat assessed as training trial latency time at 0.001 mg/kg, ip2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID313518Antiamnesic activity in scopolamine-induced memory deficit rat assessed as retention trial latency time at 0.1 mg/kg, ip after 24 hrs2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID217620Selectivity for Kv1.3 over Kv1.2 voltage-gated potassium channel subunit2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID619513Antiviral activity against HIV1 infected in human CEM-T4 cells assessed as reduction in viral protein p24 production preincubated for 24 hrs measured after 8 days by MTT assay2011Journal of medicinal chemistry, Oct-13, Volume: 54, Issue:19
Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
AID217641Selectivity for Kv1.3 over Kv1.5 voltage-gated potassium channel subunit2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID494749Inhibition of [3H]choline uptake at choline transporter 1 in mouse brain synaptosome2010Bioorganic & medicinal chemistry letters, Aug-15, Volume: 20, Issue:16
3-D-QSAR and docking studies on the neuronal choline transporter.
AID313515Antiamnesic activity in scopolamine-induced memory deficit rat assessed as retention trial latency time at 0.001 mg/kg, ip after 24 hrs2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID554308Inhibition of Leishmania major PTR12011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase.
AID217619Selectivity for Kv1.3 over Kv1.1 voltage-gated potassium channel subunit2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID1441974Neuroprotective activity against cuprizone-induced demyelination in C57BL/6J mouse corpus callosum assessed as improvement in neuronal conduction by measuring increase in amplitude of unmyelinated axon N2 wave at 10 uM relative to baseline2017Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.
AID313517Antiamnesic activity in scopolamine-induced memory deficit rat assessed as retention trial latency time at 0.01 mg/kg, ip after 24 hrs2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID619512Cytotoxicity against human CEM-T4 cells assessed as cell viability at 200 uM after 7 days by MTT assay2011Journal of medicinal chemistry, Oct-13, Volume: 54, Issue:19
Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
AID1441973Neuroprotective activity against cuprizone-induced demyelination in C57BL/6J mouse corpus callosum assessed as improvement in neuronal conduction by measuring increase in amplitude of unmyelinated axon N2 wave at 1 uM relative to baseline2017Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.
AID576612Inhibition of human ERG2011European journal of medicinal chemistry, Feb, Volume: 46, Issue:2
Predicting hERG activities of compounds from their 3D structures: development and evaluation of a global descriptors based QSAR model.
AID313502Antiamnesic activity in scopolamine-induced memory deficit rat assessed as training trial latency time at 0.01 mg/kg, ip2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID496866Anticonvulsant activity in po dosed mouse assessed as inhibition of MES-induced tonic seizures2010Journal of medicinal chemistry, Aug-12, Volume: 53, Issue:15
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists: from bench to bedside.
AID521220Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay2007Nature chemical biology, May, Volume: 3, Issue:5
Chemical genetics reveals a complex functional ground state of neural stem cells.
AID16352Dissociation constant (pKa)1980Journal of medicinal chemistry, Apr, Volume: 23, Issue:4
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 3. C-Benzylation of aminopyridines with phenolic Mannich bases. Synthesis of 1- and 3-deaza analogues of trimethoprim.
AID32128Inhibitory activity against rat brain Acetylcholinesterase using rat cortex homogenate relative to Tacrine.1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Heterodimeric tacrine-based acetylcholinesterase inhibitors: investigating ligand-peripheral site interactions.
AID1441978Inhibition of Kv1.1 (unknown origin)2017Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.
AID205269Inhibition of binding of Batrachotoxinin [3H]BTX-B to high-affinity sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 100 uM1985Journal of medicinal chemistry, Mar, Volume: 28, Issue:3
[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID205268Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM1985Journal of medicinal chemistry, Mar, Volume: 28, Issue:3
[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID313516Antiamnesic activity in scopolamine-induced memory deficit rat assessed as retention trial latency time at 0.005 mg/kg, ip after 24 hrs2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID93658Selectivity for Kv1.3 voltage-gated K+ channel over IKCa1 [Ca2+] activated K+ channel2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID217629Dissociation constant for the blockage of voltage-gated potassium channel subunit Kv1.3 in human lymphocytes2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID313501Antiamnesic activity in scopolamine-induced memory deficit rat assessed as training trial latency time at 0.005 mg/kg, ip2008Bioorganic & medicinal chemistry letters, Jan-01, Volume: 18, Issue:1
4-Aminopyridine derivatives with anticholinesterase and antiamnesic activity.
AID619514Selectivity index, ratio of CC50 for human CEM-T4 cells to EC50 for HIV1 infected human CEM-T4 cells2011Journal of medicinal chemistry, Oct-13, Volume: 54, Issue:19
Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
AID1441976Neurotoxicity in C57BL/6J mouse corpus callosum assessed as effect on amplitude of unmyelinated axon N2 wave at 10 uM relative to baseline2017Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.
AID554311Inhibition of Leishmania major DHFR at 500 uM2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase.
AID1145386Partition coefficient, log P of the compound by shake-flask technique1976Journal of medicinal chemistry, May, Volume: 19, Issue:5
Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography.
AID1441975Neurotoxicity in C57BL/6J mouse corpus callosum assessed as effect on amplitude of unmyelinated axon N2 wave at 1 uM relative to baseline2017Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.
AID240820Inhibitory concentration against IKr potassium channel2004Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18
The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.
AID217771Selectivity for Kv1.3 over Kv1.7 voltage-gated potassium channel subunit; nd = not determined2004Journal of medicinal chemistry, Apr-22, Volume: 47, Issue:9
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
AID1346692Mouse Kv4.3 (Voltage-gated potassium channels)2006British journal of pharmacology, Nov, Volume: 149, Issue:6
Pharmacological and molecular evidence for the involvement of Kv4.3 in ultra-fast activating K+ currents in murine portal vein myocytes.
AID1346635Mouse TRPV2 (Transient Receptor Potential channels)2007Molecular pharmacology, Nov, Volume: 72, Issue:5
Pharmacological characterization and molecular determinants of the activation of transient receptor potential V2 channel orthologs by 2-aminoethoxydiphenyl borate.
AID1346659Mouse Kv1.7 (Voltage-gated potassium channels)1998The Journal of biological chemistry, Mar-06, Volume: 273, Issue:10
Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7.
AID1346677Mouse Kv4.1 (Voltage-gated potassium channels)2002Proceedings of the National Academy of Sciences of the United States of America, Jan-22, Volume: 99, Issue:2
Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.
AID1346663Rat Kv1.4 (Voltage-gated potassium channels)1989The EMBO journal, Nov, Volume: 8, Issue:11
Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain.
AID1346611Human Kir7.1 (Inwardly rectifying potassium channels)1998Neuron, May, Volume: 20, Issue:5
A novel inward rectifier K+ channel with unique pore properties.
AID1346670Human Kv4.1 (Voltage-gated potassium channels)2000Genomics, Mar-01, Volume: 64, Issue:2
Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA).
AID1346668Rat Kv2.1 (Voltage-gated potassium channels)1993The Journal of general physiology, Nov, Volume: 102, Issue:5
Gating-dependent mechanism of 4-aminopyridine block in two related potassium channels.
AID1346695Rat Kv3.3 (Voltage-gated potassium channels)1992Proceedings. Biological sciences, Apr-22, Volume: 248, Issue:1321
Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel.
AID1346659Mouse Kv1.7 (Voltage-gated potassium channels)2006The Journal of general physiology, Jul, Volume: 128, Issue:1
Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
AID1346684Human Kv1.5 (Voltage-gated potassium channels)1994Molecular pharmacology, Jun, Volume: 45, Issue:6
Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.
AID1346681Mouse Kv3.1 (Voltage-gated potassium channels)1994Molecular pharmacology, Jun, Volume: 45, Issue:6
Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.
AID1346655Human Kv2.2 (Voltage-gated potassium channels)1998The American journal of physiology, 05, Volume: 274, Issue:5
Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles.
AID1346653Mouse Kv4.2 (Voltage-gated potassium channels)2006Molecular pharmacology, Mar, Volume: 69, Issue:3
1,4-Diazabicyclo[2.2.2]octane derivatives: a novel class of voltage-gated potassium channel blockers.
AID1346703Rat Kv3.2 (Voltage-gated potassium channels)2002The Journal of physiology, Jan-15, Volume: 538, Issue:Pt 2
Gating, modulation and subunit composition of voltage-gated K(+) channels in dendritic inhibitory interneurones of rat hippocampus.
AID1346671Human Kv1.8 (Voltage-gated potassium channels)2000American journal of physiology. Renal physiology, Jun, Volume: 278, Issue:6
KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.
AID1346704Rat Kv1.2 (Voltage-gated potassium channels)1994Molecular pharmacology, Jun, Volume: 45, Issue:6
Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID1802150TREK1 Assay from Article 10.1111/cbdd.12810: \\Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.\\2016Chemical biology & drug design, Dec, Volume: 88, Issue:6
Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.
AID1796455Enzyme Inhibition Assay from Article 10.1016/s0968-0896(99)00178-9: \\Dual-site binding of bivalent 4-aminopyridine- and 4-aminoquinoline-based AChE inhibitors: contribution of the hydrophobic alkylene tether to monomer and dimer affinities.\\1999Bioorganic & medicinal chemistry, Nov, Volume: 7, Issue:11
Dual-site binding of bivalent 4-aminopyridine- and 4-aminoquinoline-based AChE inhibitors: contribution of the hydrophobic alkylene tether to monomer and dimer affinities.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID1224864HCS microscopy assay (F508del-CFTR)2016PloS one, , Volume: 11, Issue:10
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).2014Journal of biomolecular screening, Jul, Volume: 19, Issue:6
A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (4,037)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990701 (17.36)18.7374
1990's1310 (32.45)18.2507
2000's1116 (27.64)29.6817
2010's793 (19.64)24.3611
2020's117 (2.90)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 53.89

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index53.89 (24.57)
Research Supply Index8.36 (2.92)
Research Growth Index4.60 (4.65)
Search Engine Demand Index93.72 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (53.89)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials134 (3.24%)5.53%
Reviews127 (3.07%)6.00%
Case Studies96 (2.32%)4.05%
Observational11 (0.27%)0.25%
Other3,773 (91.11%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (64)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Pharmaco-Diagnostic Crossover Trial for Peripheral Nerve Continuity After Trauma [NCT06003166]Phase 368 participants (Anticipated)Interventional2024-04-30Not yet recruiting
A Single-Dose, Open-Label, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Oral Fampridine-PR 10 mg in Chinese, Japanese, and Caucasian Adult Healthy Volunteers [NCT01215084]Phase 136 participants (Actual)Interventional2010-10-31Completed
Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia [NCT05613114]8 participants (Actual)Interventional2020-08-03Completed
4-aminopyridine Treatment for Nerve Injury From Radical Retro-Pubic Prostatectomy [NCT03658408]Phase 20 participants (Actual)Interventional2018-10-03Withdrawn(stopped due to This record should not have been created for this study. It is under another sponsor's account.)
Prospective, Randomized, Placebo-controlled, Phase 2 Study of 4-aminopyridine, Atenolol, or Placebo in the Treatment of Patients With Vestibular Migraine [NCT03578354]Phase 20 participants (Actual)Interventional2019-01-31Withdrawn(stopped due to Funding not acquired)
Dalfampridine Combined With Physical Therapy for Mobility Impairment in People With Multiple Sclerosis [NCT06136728]Phase 448 participants (Anticipated)Interventional2024-01-31Not yet recruiting
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 [NCT01316055]Phase 142 participants (Actual)Interventional2011-01-31Completed
Quality of Life, Efficacy and Safety of High Doses of 4-aminopyridine in Patients With Clinically Complete Chronic Spinal Cord Injury: Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial [NCT03899584]Phase 3150 participants (Actual)Interventional2019-07-17Active, not recruiting
A Single Dose Pharmaco-Diagnostic for Peripheral Nerve Continuity After Trauma [NCT04026568]Phase 2/Phase 31 participants (Actual)Interventional2021-08-17Terminated(stopped due to Study investigator left Institution)
Fampridine in MS Patients: A Cognition, Fatigue, Depression and Quality of Life Analysis [NCT03164018]111 participants (Actual)Observational2017-03-07Completed
RETRAP - A Double Blind, Randomized, Placebo Controlled Study of the Effect of the Combination of Resistance Training and Prolonged Release Fampridine in Patients With Multiple Sclerosis [NCT02143167]Phase 440 participants (Actual)Interventional2014-05-31Completed
Dalfampridine After Optic Neuritis to Improve Visual Function in Multiple Sclerosis [NCT01337986]Phase 2/Phase 353 participants (Actual)Interventional2011-05-31Completed
Double-Blind, Placebo-Controlled, 20-Week, Parallel Group Study to Evaluate Safety, Tolerability and Activity of Oral Fampridine-SR in Subjects With Multiple Sclerosis [NCT00053417]Phase 2206 participants (Actual)Interventional2003-02-28Completed
Open-Label Extension Study to Evaluate the Safety and Tolerability of Oral Fampridine SR in Canadian Subjects With Multiple Sclerosis Who Participated in Acorda Extension Trials [NCT01235221]Phase 338 participants (Actual)Interventional2010-12-31Completed
A Multicenter, 18-week Open Label Safety and Efficacy Trial of Dalfampridine in Primary Lateral Sclerosis [NCT02868567]Phase 135 participants (Anticipated)Interventional2016-03-31Active, not recruiting
Efficacy of Sustained-release Oral Dalfampridine on Upper Extremity Function in Patients With Multiple Sclerosis: a Pilot Study [NCT02259361]Phase 430 participants (Anticipated)Interventional2014-11-30Not yet recruiting
Prolonged-release Fampridine as Adjunct Therapy to Active Motor Training in MS Patients: a Phase IV, Double-blind, Placebo-controlled Study. [NCT02146534]Phase 444 participants (Actual)Interventional2013-12-31Completed
Short and Long Term Fampridine Treatment in Persons With Multiple Sclerosis: Cognitive and Motor Performances [NCT02849782]Phase 489 participants (Actual)Interventional2014-02-04Completed
Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR (10 mg b.i.d. [Bis in Die, Twice Daily]) in Patients With Multiple Sclerosis [NCT00483652]Phase 3240 participants (Actual)Interventional2007-05-31Completed
4-aminopyridine Treatment for Nerve Injury Resulting From Radical Retro-Pubic Prostatectomy [NCT03701581]Phase 2/Phase 370 participants (Anticipated)Interventional2021-06-05Active, not recruiting
A Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Oral Prolonged-Release Fampridine (BIIB041) in Japanese Subjects With Multiple Sclerosis Followed by an Open-Label Safety Extension [NCT01917019]Phase 3101 participants (Actual)Interventional2013-08-31Completed
Dalfampridine Treatment for Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) [NCT01975324]Phase 420 participants (Actual)Interventional2013-07-31Completed
Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action [NCT01645787]Phase 2/Phase 311 participants (Actual)Interventional2012-06-30Completed
A Randomized Controlled Double-blind Cross-over Trial of Dalfampridine ER for Effect on Ambulatory Activity in People With Multiple Sclerosis [NCT01356940]Phase 443 participants (Actual)Interventional2010-11-30Completed
Effects of Physical Therapy and Dalfampridine on Functional Mobility and Lower Extremity Strength in Non Ambulatory Persons With Multiple Sclerosis [NCT05859802]Phase 2/Phase 335 participants (Actual)Interventional2011-07-13Completed
A Multicenter, Multinational, Observational Study to Collect Information on Safety and to Document the Drug Utilization of Fampyra® When Used In Routine Medical Practice (LIBERATE) [NCT01480063]4,734 participants (Actual)Observational2012-04-16Completed
Muscle Strain in Multiple Sclerosis Patients Measured by Ultrasound Speckle Tracking [NCT03847545]48 participants (Actual)Interventional2018-12-12Completed
Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Healthy Subjects [NCT04516603]Phase 20 participants (Actual)Interventional2020-10-01Withdrawn(stopped due to Changement of study design. Restart spring 2021.)
A Double-Blind, Placebo-Controlled, Crossover Study in Subjects With Cerebral Palsy to Evaluate the Safety and Tolerability and the Effect on Sensorimotor Function of Dalfampridine-ER [NCT01468350]Phase 135 participants (Actual)Interventional2011-12-31Completed
An Open-label, Proof of Concept Study to Evaluate Multiple Gait and Balance Parameters After Withdrawal of Dalfampridine-ER 10mg in Subjects With MS [NCT01535664]20 participants (Actual)Observational2012-01-31Completed
Fampridine Pregnancy Exposure Registry [NCT01532154]1 participants (Actual)Observational [Patient Registry]2015-08-31Terminated(stopped due to Due to low enrollment, registration closed in agreement with the Regulatory Agency)
Phase 2 Study of 4-Aminopyridine for the Treatment of Episodic Ataxia Type 2 [NCT01543750]Phase 20 participants (Actual)InterventionalWithdrawn
Assessment of Chronic GBS Improvement With Use of 4-AP [NCT00056810]Phase 230 participants Interventional2002-09-30Completed
Effects of Dalfampridine on Cognition in Multiple Sclerosis [NCT02006160]Phase 2/Phase 361 participants (Actual)Interventional2011-12-31Completed
Effect of Dalfampridine on Gait Impairment, Cognition and Fatigue in Egyptian Patients With Multiple Sclerosis [NCT05730738]100 participants (Anticipated)Interventional2021-06-01Recruiting
Restoring Lost Functions After Spinal Cord Injury: Combination Therapy With Dalfampridine and Locomotor Training for Persons With Chronic, Motor Incomplete Spinal Cord Injury [NCT01621113]Phase 227 participants (Actual)Interventional2012-06-30Completed
Fampyra Outcome Measures Study: a Study of Different Outcome Measures on the Effect of Fampyra [NCT01656148]Phase 4108 participants (Actual)Interventional2012-06-30Completed
Does Fampridine SR Improve Cognitive Fatigue in Multiple Sclerosis Patients? A Cross Over Study [NCT01667497]Phase 2/Phase 360 participants (Actual)Interventional2012-09-30Completed
Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis. Randomized, Blinded, Placebo-controlled Clinical Trial. [NCT02280096]Phase 224 participants (Actual)Interventional2014-10-31Completed
An Extension Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of Dalfampridine Extended-Release Tablets. for the Treatment of Chronic Post-Ischemic Stroke Walking Deficits . [NCT02422940]Phase 3294 participants (Actual)Interventional2015-04-30Terminated
Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis [NCT02391961]Phase 223 participants (Actual)Interventional2015-04-01Completed
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 [NCT01328379]Phase 3430 participants (Actual)Interventional2011-03-31Completed
Double-Blind, Placebo-Controlled, 12-Week Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR in Subjects With Moderate to Severe Spasticity Resulting From Chronic, Incomplete Spinal Cord Injury [NCT00041717]Phase 3213 participants (Actual)Interventional2002-07-31Completed
A Phase IIb, Double-blind, Randomized, Mono-center, Placebo-controlled Study With Crossover Design Characterizing the Effects of Prolonged-release Fampridine Treatment on Ambulatory Function in Patients With Multiple Sclerosis Using Detailed Gait Analysis [NCT01576354]Phase 270 participants (Anticipated)Interventional2012-03-31Active, not recruiting
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Exploratory Study to Assess the Effect of Treatment With Prolonged-Release Fampridine (BIIB041) 10 mg Twice Daily on Walking Ability and Balance in Subjects With Multiple Sclerosis [NCT01597297]Phase 2132 participants (Actual)Interventional2012-08-31Completed
Double-Blind, Placebo-Controlled, 21-Week, Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR in Subjects With Multiple Sclerosis [NCT00127530]Phase 3300 participants (Actual)Interventional2005-05-31Completed
A Randomized Trial to Evaluate Ampyra for Gait Impairment in Parkinson's Disease [NCT01491022]Phase 1/Phase 222 participants (Actual)Interventional2012-07-31Completed
This is a Multi-center, Double-blind, Three Arm, Parallel Group, Placebo-controlled, Randomized Study Designed to Evaluate the Efficacy, Safety and Tolerability of Dalfampridine. [NCT02271217]Phase 3377 participants (Actual)Interventional2014-12-31Completed
The Effect of Dalfampridine (4-aminopyridine) on Genioglossus Muscle Activity During Wakefulness and Sleep in Healthy Control Subjects [NCT02656160]Phase 213 participants (Actual)Interventional2016-01-31Completed
The Effect of Fampridine-SR on Visual Function in Poorly Recovered Optic Neuritis in Persons With MS [NCT04148781]Early Phase 120 participants (Anticipated)Interventional2022-03-22Recruiting
Effects of 4-AP on Functional Recovery After Spinal Cord Injury [NCT05447676]Early Phase 144 participants (Anticipated)Interventional2022-06-30Recruiting
Phase 3 Open-Label Extension Study to Evaluate the Safety, Tolerability and Activity of Oral Fampridine-SR in Patients With Multiple Sclerosis [NCT00654927]Phase 3177 participants (Actual)Interventional2003-11-30Completed
A Phase 2b Study of Dalfampridine 10mg Extended Release Tablet in Subjects With Chronic Deficits After Ischemic Stroke [NCT01605825]Phase 283 participants (Actual)Interventional2012-05-31Completed
Phase 3 Open-Label Extension Study to Evaluate the Safety, Tolerability and Activity of Oral Fampridine-SR in Patients With Multiple Sclerosis Who Participated in the MS-F204 Trial [NCT00649792]Phase 3214 participants (Actual)Interventional2007-08-31Completed
Double-Blind, Placebo-Controlled Crossover Trial on the Safety and Efficacy of Sustained-Release Dalfampridine in Transverse Myelitis (Re-Launch) [NCT02166346]Phase 224 participants (Actual)Interventional2014-02-28Completed
Phase 3 Open-Label Extension Study to Evaluate the Safety, Tolerability and Activity of Oral Fampridine-SR in Subjects With Multiple Sclerosis Who Participated in the MS-F203 Trial [NCT00648908]Phase 3269 participants (Actual)Interventional2006-06-30Completed
Dalfampridine to Improve Imbalance in Multiple Sclerosis: A Pilot Study [NCT01444300]Phase 224 participants (Actual)Interventional2011-09-30Completed
Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Individuals With Post COVID-19 Condition With Subjective Cognitive Impairment [NCT05274477]44 participants (Anticipated)Interventional2022-06-28Recruiting
A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Assess the Long-Term Efficacy and Safety of Prolonged Release Fampridine (BIIB041) 10 mg, Administered Twice Daily in Subjects With Multiple Sclerosis (ENHANCE) [NCT02219932]Phase 3646 participants (Actual)Interventional2014-09-30Completed
Therapeutic Effect of Dalfampridine on Gait Incoordination in Spinocerebellar Ataxias- A Randomized, Double-blinded, Placebo-controlled, Crossover Clinical Trial [NCT01811706]20 participants (Actual)Interventional2013-02-28Completed
An Open-Label, Multicenter, Multinational Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) 10 mg Twice Daily on Quality of Life as Reported by Subjects With Multiple Sclerosis [NCT01480076]Phase 4901 participants (Actual)Interventional2012-02-29Completed
Randomized Placebo-controlled Phase II Cross-over Study on the Influence of Fampridine on Working Memory in Healthy Subjects [NCT04652557]Phase 244 participants (Actual)Interventional2021-11-01Completed
A Phase IV Double Blind, Randomized, Placebo Controlled, Crossover Study of the Effectiveness of Oral Fampridine in Improving Upper Limb Function in Progressive Multiple Sclerosis [NCT02208050]Phase 464 participants (Actual)Interventional2014-02-21Completed
Double-Blind, Placebo-Controlled, 12-Week Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR in Subjects With Moderate to Severe Spasticity Resulting From Chronic, Incomplete Spinal Cord Injury [NCT01683838]Phase 3204 participants (Actual)Interventional2002-06-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00041717 (2) [back to overview]Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
NCT00041717 (2) [back to overview]Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment
NCT00053417 (1) [back to overview]Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test
NCT00127530 (1) [back to overview]Timed Walk Responders (Patients Who Showed Consistent Improvement on the Timed-25 Foot Walk)
NCT00483652 (2) [back to overview]Change in Lower Extremity Manual Muscle Test [LEMMT]
NCT00483652 (2) [back to overview]Responders Based Upon the Timed 25-Foot Walk [T25FW]
NCT00648908 (5) [back to overview]Expanded Disability Status Scale (EDSS)
NCT00648908 (5) [back to overview]Subject Global Impression (SGI)
NCT00648908 (5) [back to overview]Timed 25 Foot Walk (T25FW)
NCT00648908 (5) [back to overview]Clinician Global Impression of Change (CGIC)
NCT00648908 (5) [back to overview]Summary of Treatment Emergent Adverse Events (TEAE).
NCT00649792 (5) [back to overview]Summary of Treatment Emergent Adverse Events (TEAE).
NCT00649792 (5) [back to overview]Clinician's Global Impression (CGI)
NCT00649792 (5) [back to overview]Expanded Disability Status Scale (EDSS)
NCT00649792 (5) [back to overview]Subject Global Impression (SGI)
NCT00649792 (5) [back to overview]Timed 25-Foot Walk (T25FW)
NCT00654927 (5) [back to overview]Summary of Treatment Emergent Adverse Events (TEAE).
NCT00654927 (5) [back to overview]Subject Global Impression (SGI)
NCT00654927 (5) [back to overview]Expanded Disability Status Scale (EDSS)
NCT00654927 (5) [back to overview]Clinician Global Impression of Change (CGIC)
NCT00654927 (5) [back to overview]Timed 25 Foot Walk (T25FW)
NCT01316055 (3) [back to overview]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.
NCT01316055 (3) [back to overview]The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12).
NCT01316055 (3) [back to overview]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.
NCT01328379 (7) [back to overview]Change From Baseline in MSWS-12 at Visit 2
NCT01328379 (7) [back to overview]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).
NCT01328379 (7) [back to overview]Change From Baseline in Six-Minute Walk Distance at Visit 2
NCT01328379 (7) [back to overview]Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3.
NCT01328379 (7) [back to overview]Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3
NCT01328379 (7) [back to overview]Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3.
NCT01328379 (7) [back to overview]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).
NCT01337986 (11) [back to overview]Dalfampridine Effect on Quality of Life Change From Baseline.
NCT01337986 (11) [back to overview]Visual Evoked Potential P100 Latency Per Treatment Arm
NCT01337986 (11) [back to overview]Percentage of Eyes That Improved by One-line (5 Letters)
NCT01337986 (11) [back to overview]Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
NCT01337986 (11) [back to overview]Percentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart
NCT01337986 (11) [back to overview]Changes in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).
NCT01337986 (11) [back to overview]Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores
NCT01337986 (11) [back to overview]Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
NCT01337986 (11) [back to overview]Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1
NCT01337986 (11) [back to overview]Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1
NCT01337986 (11) [back to overview]Odds Ratio Quartile of Visual Field Index
NCT01356940 (2) [back to overview]Stepcount
NCT01356940 (2) [back to overview]Peak Activity Index
NCT01444300 (3) [back to overview]Change in Automatic Postural Response (APR )Latency
NCT01444300 (3) [back to overview]Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores
NCT01444300 (3) [back to overview]Change in Timed 25 Foot Walking Speed
NCT01468350 (1) [back to overview]Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP)
NCT01480076 (35) [back to overview]Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders
NCT01480076 (35) [back to overview]Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders
NCT01480076 (35) [back to overview]Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
NCT01480076 (35) [back to overview]Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12
NCT01480076 (35) [back to overview]Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
NCT01480076 (35) [back to overview]Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
NCT01480076 (35) [back to overview]Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12
NCT01480076 (35) [back to overview]Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
NCT01491022 (6) [back to overview]Timed 25-foot Walk Test (T25FW)
NCT01491022 (6) [back to overview]Freezing of Gait Questionnaire (FOGQ)
NCT01491022 (6) [back to overview]Change in Velocity
NCT01491022 (6) [back to overview]Change in Stride Legth
NCT01491022 (6) [back to overview]United Parkinson's Disease Rating Scale Score(UPDRS) ,
NCT01491022 (6) [back to overview]Timed Up and Go (TUG) Score
NCT01535664 (5) [back to overview]Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
NCT01535664 (5) [back to overview]Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
NCT01535664 (5) [back to overview]Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
NCT01535664 (5) [back to overview]Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
NCT01535664 (5) [back to overview]Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
NCT01605825 (1) [back to overview]Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs)
NCT01683838 (9) [back to overview]Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores
NCT01683838 (9) [back to overview]Adjusted Mean Change in Subject Bowel Function Diary Scores
NCT01683838 (9) [back to overview]Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
NCT01683838 (9) [back to overview]Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores
NCT01683838 (9) [back to overview]Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores
NCT01683838 (9) [back to overview]Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score
NCT01683838 (9) [back to overview]Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores
NCT01683838 (9) [back to overview]Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores
NCT01683838 (9) [back to overview]Change From Baseline in Mean International Index of Erectile Function (IIEF) Score
NCT01811706 (3) [back to overview]Change in Timed 25 Feet Walking Test (T25FW)
NCT01811706 (3) [back to overview]Change in Scale of Assessment and Rating of Ataxia (SARA)
NCT01811706 (3) [back to overview]Biomechanical Assessment of Gait (BAG)-Stride Length
NCT02006160 (1) [back to overview]Symbol Digit Modalities Test
NCT02166346 (2) [back to overview]Upper and Lower Extremity Muscle Strength Measurements
NCT02166346 (2) [back to overview]Walking Speed During Timed 25-foot Walk
NCT02208050 (7) [back to overview]Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.
NCT02208050 (7) [back to overview]Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)
NCT02208050 (7) [back to overview]Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)
NCT02208050 (7) [back to overview]The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)
NCT02208050 (7) [back to overview]Mean Scores of MSIS-29 - Fampridine and Placebo
NCT02208050 (7) [back to overview]Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.
NCT02208050 (7) [back to overview]Mean Scores in DASH - Fampridine and Placebo.
NCT02219932 (5) [back to overview]Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks
NCT02219932 (5) [back to overview]Proportion of Participants Achieving a Mean Improvement of ≥ 8 Points From Baseline on the Multiple Sclerosis Walking Scale (MSWS-12) Over 24 Weeks
NCT02219932 (5) [back to overview]Change From Baseline in ABILHAND Score Over 24 Weeks
NCT02219932 (5) [back to overview]Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks
NCT02219932 (5) [back to overview]Proportion of Participants Achieving a Mean Improvement From Baseline of ≥ 15% in Timed Up and Go (TUG) Speed Over 24 Weeks
NCT02271217 (2) [back to overview]Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary)
NCT02271217 (2) [back to overview]Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12
NCT02280096 (12) [back to overview]Improved Physical Capacity
NCT02280096 (12) [back to overview]Tower Of London (TOL). Total Moves and Total Correct Moves
NCT02280096 (12) [back to overview]Tower Of London (TOL). Execution Time and Problem-solving Time
NCT02280096 (12) [back to overview]Number of Participants With Abnormal Studies
NCT02280096 (12) [back to overview]Wisconsin Card Sorting Test (WCST)
NCT02280096 (12) [back to overview]Walk
NCT02280096 (12) [back to overview]Rey-Osterrieth Complex Figure Test (ROCF)
NCT02280096 (12) [back to overview]Integrated Program of Neuropsychological Exploration Test Barcelona
NCT02280096 (12) [back to overview]Five Digit Test (FDT). Processing Speed
NCT02280096 (12) [back to overview]Fatigue
NCT02280096 (12) [back to overview]Color Trails Test (CTT)
NCT02280096 (12) [back to overview]The Brief Repeatable Battery of Rao
NCT02391961 (7) [back to overview]Pulse Size Ratio (PSR): Abducting/Adducting Eye Ratio for Saccadic Peak Velocity.
NCT02391961 (7) [back to overview]National Eye Institute (NEI) Visual Function Questionnaire 25 (VFQ-25)
NCT02391961 (7) [back to overview]Reading Acuity (RA)
NCT02391961 (7) [back to overview]10-Item Neuro-Ophthalmic Supplement (NOS)
NCT02391961 (7) [back to overview]Gait Assessment
NCT02391961 (7) [back to overview]Pulse Time Delay (PTD): Time Difference Between Onset of the Saccade in the Adducting Eye and Onset of the Saccade in the Abducting Eye.
NCT02391961 (7) [back to overview]Maximum Reading Speed (MRS)
NCT02422940 (8) [back to overview]Change From Baseline on the 10 Meter Walk Test (10MWT)
NCT02422940 (8) [back to overview]Change From Baseline on the 12-item Health Survey (SF-12)
NCT02422940 (8) [back to overview]Change From Baseline on the Stroke Impact Scale (SIS)
NCT02422940 (8) [back to overview]Subject Global Impression (SGI)
NCT02422940 (8) [back to overview]Change From Baseline on the Timed up and Go (TUG) Test
NCT02422940 (8) [back to overview]Change From Baseline on the Two-Minute Walk Test (2MinWT)
NCT02422940 (8) [back to overview]Change From Baseline on the Walking Impact Scale (Walk-12)
NCT02422940 (8) [back to overview]The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months.
NCT02656160 (2) [back to overview]Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)
NCT02656160 (2) [back to overview]Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration).
NCT04026568 (1) [back to overview]Subjective Return of Sensation

Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity

The Ashworth Score is the average rating (based on a scale of 1 to 5) of four lower extremity muscle groups; left and right knee flexors and extensors (hamstrings and quadriceps muscles). A higher Ashworth Score indicates a greater degree of abnormal muscle tone (spasticity) and a negative change in score indicates improvement. (NCT00041717)
Timeframe: Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day-0.19
Placebo-0.15

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Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment

This questionnaire asked the patient to evaluate the effects of investigational drug on his/her quality of life during the preceding week using a 7-point scale (from 1=terrible to 7=delighted). A positive change score in SGI indicates improved outcome. (NCT00041717)
Timeframe: Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day-0.2
Placebo-0.1

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Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test

The primary efficacy variable was the percent change from baseline in average walking speed measured using the Timed 25-Foot Walk Test during the 12-week stable dose period (the average of Study Days 56, 84, and 112), relative to the mean at baseline (placebo run-in period, the average of Study Days 7 and 14). (NCT00053417)
Timeframe: Baseline (placebo run-in period); 12-week stable dose period

Interventionpercent change (Median)
Placebo1.2
10 mg Fampridine Twice a Day (b.i.d.)7.5
15 mg Fampridine b.i.d.9.7
20 mg Fampridine b.i.d.6.9

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Timed Walk Responders (Patients Who Showed Consistent Improvement on the Timed-25 Foot Walk)

Patients who showed a faster walking speed for at least three of the four on-drug visits during the double-blind treatment period as compared to the maximum speed for any of the five off-drug visits. (NCT00127530)
Timeframe: Days 14, 42, 70 and 98 of treatment, corresponding to the four on-drug visits during double-blind treatment period.

InterventionParticipants (Number)
Placebo- Sugar Pill6
Fampridine-SR78

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Change in Lower Extremity Manual Muscle Test [LEMMT]

Evaluator rated strength in hip flexors, knee flexors, knee extensors, and ankle dorsiflexors on the following scale: best value = 5.0 (normal muscle strength), worst value = 0.0 (absence of any voluntary contraction). A positive shift in LEMMT score shows improvement in strength. Change in LEMMT scores for the secondary efficacy measure was found by averaging the LEMMT scores on days 14, 28, 42, and 56 (double-blind treatment period) and subtracting the baseline LEMMT score. (NCT00483652)
Timeframe: Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77

Interventionunits on a scale (Mean)
Fampridine-SR 10 mg b.i.d. Treatment0.09
Placebo Treatment0.04

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Responders Based Upon the Timed 25-Foot Walk [T25FW]

A responder is a patient who showed faster walking speed for at least 3 visits out of a possible 4 during the double-blind period than the maximum value achieved in the 5 non-double-blind no-treatment visits (4 before the double-blind period and one after) (NCT00483652)
Timeframe: Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77

Interventionparticipants (Number)
Fampridine-SR 10 mg b.i.d. Treatment51
Placebo Treatment11

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Expanded Disability Status Scale (EDSS)

"Each patient, based on their baseline neurological exam, are scored according to the EDSS~The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death) at the Screening Visit, Visit 6, and Final Visit or Early Termination Visit if applicable." (NCT00648908)
Timeframe: Screening visit, visit 6 and every 24 months thereafter

Interventionunits on a scale (Mean)
(N=268) Baseline(N=192) >94-120 Weeks(N= 148) >198-224 Weeks
Fampridine-SR5.785.956.16

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Subject Global Impression (SGI)

"Patients asked to complete a Subject Impression questionnaire rating his/her impression of the effects of study drug during the preceding week, specifically in regards to signs and symptoms associated with Multiple Sclerosis (MS).~For the SGI, the potential responses to the effects of the investigational drug during the preceding week were 1=terrible, 2=unhappy, 3=mostly dissatisfied, 4=neutral/ mixed, 5=mostly satisfied, 6=pleased, and 7=delighted." (NCT00648908)
Timeframe: visit 1 and every clinic visit

Interventionunits on a scale (Mean)
(N=268) >0-8 Weeks(N=247) >8-16 Weeks(N=247) >16-42 Weeks(N=230) >42-68 Weeks(N=214) >68-94 Weeks(N=203) >94-120 Weeks(N=191) >120-146 Weeks(N=182) >146-172 Weeks(N=168) >172-198 Weeks(N=159) >198-224 Weeks(N=77) >224-250 Weeks(N=13) >250-276 Weeks
Fampridine-SR4.854.794.864.804.955.035.145.095.135.165.205.46

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Timed 25 Foot Walk (T25FW)

(NCT00648908)
Timeframe: Week 2, 14, 26, continuing every 26 weeks until the Final Visit

Interventionfeet/second (Mean)
(N=265) >0-8 Weeks(N=242) >8-16 Weeks(N=249) >16-42 Weeks(N=222) >42-68 Weeks(N=204) >68-94 Weeks(N=190) >94-120 Weeks(N=177) >120-146 Weeks(N=156) >146-172 Weeks(N=143) >172-198 Weeks(N=137) >198-224 Weeks(N=58) >224-250 Weeks(N=7) >250-276 Weeks
Fampridine-SR 10mg (Twice a Day)2.352.272.282.232.182.152.142.142.142.151.981.56

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Clinician Global Impression of Change (CGIC)

"Investigator's overall impression of the patients neurological status and general state of health related to his/her participation in the study; specifically signs and symptoms associated with MS.~The potential responses were 1=very much improved, 2=much improved, 3=somewhat improved, 4=no change, 5=somewhat worse, 6=much worse, and 7=very much worse." (NCT00648908)
Timeframe: visit 1 and every clinic visit

Interventionunits on a scale (Mean)
(N=267) >0-8 Weeks(N=248) >8-16 Weeks(N=256) >16-42 Weeks(N=233) >42-68 Weeks(N=215) >68-94 Weeks(N=203) >94-120 Weeks(N=194) >120-146 Weeks(N=179) >146-172 Weeks(N=167) >172-198 Weeks(N=160) >198-224 Weeks(N=76) >224-250 Weeks(N=13) >250-276 Weeks
Fampridine-SR3.383.563.553.633.663.593.693.853.753.933.973.39

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Summary of Treatment Emergent Adverse Events (TEAE).

All adverse events reported were treatment emergent. Therefore, events that had a date of onset, or worsening, on or after the start of the open-label drug and up to 14 days after the last dose (for non-serious events) or up to 30 days after the last dose (for SAEs) were summarized. Any abnormal clinically significant changes in physical examination, medical history, clinical laboratory testing, 12-lead ECG, and standard EEG testing were captured as adverse events. (NCT00648908)
Timeframe: up to 5 years

InterventionParticipants (Number)
Patients with Any TEAEPatients with Any Serious AEPatients with Any Possibly/Probably Related AEPatients Withdrawn due to AEPatients who DiedMaximum Severity /Patients with Any Mild TEAEMaximum Severity /Patients with Any Moderate TEAEMaximum Severity /Patients with Any Severe TEAE
Fampridine-SR 10mg (Twice a Day)264947737416137111

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Summary of Treatment Emergent Adverse Events (TEAE).

All adverse events reported were treatment emergent. Therefore, events that had a date of onset, or worsening, on or after the start of the open-label drug and up to 14 days after the last dose (for non-serious events) or up to 30 days after the last dose (for SAEs) were summarized. Any abnormal clinically significant changes in physical examination, medical history, clinical laboratory testing, 12-lead ECG, and standard EEG testing were captured as adverse events. (NCT00649792)
Timeframe: up to 40 months

Interventionparticipants (Number)
Patients with Any TEAEPatients with Any Serious TEAEPatients with Any Treatment-Related AEPatients Withdrawn due to AEPatients who DiedMaximum Severity/Paitents with Any TEAE - MildMaximum Severity/Patients with Any TEAE - ModerateMaximum Severity/Patients with Any TEAE - Severe
Fampridine-SR2053946712912056

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Clinician's Global Impression (CGI)

The potential responses were 1=very much improved, 2=much improved, 3=somewhat improved, 4=no change, 5=somewhat worse, 6=much worse, and 7=very much worse. (NCT00649792)
Timeframe: Visit 1 and every clinic visit thereafter

Intervention1-7 scale rating (Mean)
(N=213) >0-8 Weeks(N=202) >8-16 Weeks(N=208) >16-42 Weeks(N=181) >42-68 Weeks(N=172) >68-94 Weeks(N=168) >94-120 Weeks(N=154) >120-146 Weeks(N=35) >146-172 Weeks(N=2) >172-198 Weeks
Fampridine-SR3.383.273.483.423.583.663.653.962.50

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Expanded Disability Status Scale (EDSS)

The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death) (NCT00649792)
Timeframe: The Screening Visit, Visit 6, Final Visit or Early Termination Visit (if applicable)

Intervention0-10 rating scale (Mean)
(N=213) Baseline(N=163) >94-120 Weeks
Fampridine-SR5.645.86

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Subject Global Impression (SGI)

For the SGI, the potential responses to the effects of the investigational drug during the preceding week were 1=terrible, 2=unhappy, 3=mostly dissatisfied, 4=neutral/ mixed, 5=mostly satisfied, 6=pleased, and 7=delighted. (NCT00649792)
Timeframe: Visit 1 and every clinic visit thereafter (other than the follow-up visit)

Intervention1-7 scale rating (Mean)
(N=214) >0-8 Weeks(N=200) >8-16 Weeks(N=199) >16-42 Weeks(N=183) >42-68 Weeks(N=173) >68-94 Weeks(N=167) >94-120 Weeks(N=153) >120-146 Weeks(N=35) >146-172 Weeks(N=2) >172-198 Weeks
Fampridine-SR4.674.704.775.044.954.975.154.945.50

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Timed 25-Foot Walk (T25FW)

(NCT00649792)
Timeframe: Week 2, 14, 26, continuing every 26 weeks until the Final Visit

Interventionfeet/seconds (Mean)
(N=209) >0-8 Weeks(N=197) >8-16 Weeks(N=201) >16-42 Weeks(N=172) >42-68 Weeks(N=160) >68-94 Weeks(N=151) >94-120 Weeks(N=143) >120-146 Weeks(N=33) >146-172 Weeks(N=2) >172-198 Weeks
Fampridine-SR2.602.532.522.462.372.352.272.171.85

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Summary of Treatment Emergent Adverse Events (TEAE).

All adverse events reported were treatment emergent. Therefore, events that had a date of onset, or worsening, on or after the start of the open-label drug and up to 14 days after the last dose (for non-serious events) or up to 30 days after the last dose (for SAEs) were summarized. Any abnormal clinically significant changes in physical examination, medical history, clinical laboratory testing, 12-lead ECG, and standard EEG testing were captured as adverse events. (NCT00654927)
Timeframe: over 7 years (2004-2011)

Interventionparticipants (Number)
Patients with Any AEPatients with Any Serious AEPatients with Any Possibly/Probably Related AEPatients withdrawn due to AEPatients who DiedMaximum Severity/Patients with Any TEAE -MildMaximum Severity/Patients with Any TEAE -ModerateMaximum Severity/Patients with Any TEAE -Severe
Fampridine-SR b.i.d.176651023451066100

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Subject Global Impression (SGI)

The patient was asked to complete a Subject Global Impression (SGI) questionnaire at Visit 1 and every study visit thereafter except the Follow-up visit. This questionnaire asked the patient to rate the effects of the investigational drug on his/her physical well-being during the preceding week, using a 1 to 7 point scale (1 = terrible, 7 = delighted) (NCT00654927)
Timeframe: visit 1 and every clinic visit

Interventionunits on a scale (Mean)
(N=176) >0-8 Weeks(N=168) >8-16 Weeks(N=163) >16-42 Weeks(N=148) >42-68 Weeks(N=137)>68-94 Weeks(N=128) >94-120 Weeks(N=124) >120-146 Weeks(N=114) >146-172 Weeks(N=102) >172-198 Weeks(N=91) >198-224 Weeks(N=88) >224-250 Weeks(N=84) >250-276 Weeks(N=81) >276-302 Weeks(N=74) >302-328 Weeks(N=12) >328-354 Weeks
Fampridine-SR b.i.d.4.794.704.714.424.674.704.734.764.845.155.105.044.915.285.08

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Expanded Disability Status Scale (EDSS)

"Based on the baseline neurological exam, each patient was scored according to the Expanded Disability Status Scale, which rates disability on a 0 to 10 scale (0 = normal neurologic examination, 10 = death)~*EDSS assessments were not well synchronized to study period because of wide differences in interval between screening and initiation" (NCT00654927)
Timeframe: Screening visit, visit 6 and every 24 months thereafter

Interventionunits on a scale (Mean)
(N=166) Baseline(N=92) >8-16 Weeks(N=114) >42-68 Weeks(N=56) >146-172 Weeks
Fampridine-SR b.i.d.6.046.146.266.03

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Clinician Global Impression of Change (CGIC)

The CGIC was based on the Investigator's overall impression of the patient's neurological status and general state of health related to his or her participation in the study, specifically in regard to signs and symptoms associated with MS. Neurological status was rated according to a 1 to 7 point scale (1 = very much improved, 7 = very much worse) (NCT00654927)
Timeframe: visit 1 and every clinic visit

Interventionunits on a scale (Median)
(N=176) >0-8 Weeks(N=168) >8-16 Weeks(N=163) >16-42 Weeks(N=148) >42-68 Weeks(N=137) >68-94 Weeks(N=128) >94-120 Weeks(N=124) >120-146 Weeks(N=116) >146-172 Weeks(N=102) >172-198 Weeks(N=92) >198-224 Weeks(N=87) >224-250 Weeks(N=83) >250-276 Weeks(N=80) >276-302 Weeks(N=73) >302-328 Weeks(N=13) >328-354 Weeks
Fampridine-SR b.i.d.3.373.473.603.803.833.763.703.963.893.753.793.874.294.273.81

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Timed 25 Foot Walk (T25FW)

(NCT00654927)
Timeframe: Screening visit, visit 4, every 12 weeks thereafter, Last Regular Visit, Follow Up Visit and Early Termination Visit

Interventionfeet/second (Mean)
(N=153) Baseline(N=1) >0-8 Weeks(N=134) >8-16 Weeks(N=141) >16-42 Weeks(N=127) >42-68 Weeks(N=111) >68-94 Weeks(N=103) >94-120 Weeks(N=92) >120-146 Weeks(N=86) >146-172 Weeks(N=76) >172-198 Weeks(N=66) >198-224 Weeks(N=56) >224-250 Weeks(N=52) >250-276 Weeks(N=54) >276-302 Weeks(N=50) >302-328 Weeks(N=10) >328-354 Weeks
Fampridine-SR b.i.d.1.871.982.092.021.821.851.771.881.841.931.822.052.031.961.981.89

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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.

(NCT01316055)
Timeframe: 7 days

Interventionnanogram/milliliter (Geometric Mean)
Healthy: Dalfampridine-ER 7.5 mg20.61
Mild Renal: Dalfampridine-ER 7.5 mg33.92
Moderate Renal: Dalfampridine-ER 7.5 mg46.69

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The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12).

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. (NCT01316055)
Timeframe: 0 and 1,2,3,4,5,6,8, and 12 hours after the last dose

Interventionhour*nanogram/milliliter (Geometric Mean)
Healthy: Dalfampridine-ER 7.5 mg157.8
Mild Renal: Dalfampridine-ER 7.5 mg276.5
Moderate Renal: Dalfampridine-ER 7.5 mg415.3

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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.

(NCT01316055)
Timeframe: 7 days

Interventionliter/hour (Geometric Mean)
Healthy: Dalfampridine-ER 7.5 mg47.54
Mild Renal: Dalfampridine-ER 7.5 mg27.12
Moderate Renal: Dalfampridine-ER 7.5 mg18.06

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Change From Baseline in MSWS-12 at Visit 2

"The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices.~For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100.~MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48" (NCT01328379)
Timeframe: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )

Interventionscores on a scale (Mean)
Placebo-9.48
Dalfampridine-ER 5mg-9.54
Dalfampridine-ER 10mg-10.04

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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).

"The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability.~A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study." (NCT01328379)
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)

Interventionfeet per second (Mean)
Placebo0.363
Dalfampridine-ER 5mg0.423
Dalfampridine-ER 10mg0.478

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Change From Baseline in Six-Minute Walk Distance at Visit 2

The Six-Minute Walk, a test of endurance, measures the distance that a patient can walk in a period of 6 minutes. Six-minute walk distance will be reported in feet. (NCT01328379)
Timeframe: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )

InterventionFeet (Mean)
Placebo41.7
Dalfampridine-ER 5mg76.8
Dalfampridine-ER 10mg128.6

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Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3.

The EQ-5D is a brief questionnaire that asks patients to rate general state of health. The VAS score rates the general state of health of a patient with 100 for the best imaginable health state and 0 for the worst imaginable health state. (NCT01328379)
Timeframe: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Interventionunits on a scale (Mean)
Placebo7.0
Dalfampridine-ER 5mg2.6
Dalfampridine-ER 10mg4.2

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Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3

"The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices.~For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100.~MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48" (NCT01328379)
Timeframe: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Interventionscores on a scale (Mean)
Placebo-8.35
Dalfampridine-ER 5mg-9.73
Dalfampridine-ER 10mg-11.10

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Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3.

"Patients completed a brief, generic health status questionnaire: The five specific dimensional scores value patients' health related to mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each question has 3 distinguishable choices that can be analyzed using a 3-point scale (i.e. 1 = no problem, 2=some problems and 3= extreme problems).~A response of 1 indicates that the patient has no problem with the dimension tested and a response of 3 indicates that the patient has extreme problems with the dimension tested. For each visit, the average score of 5 dimensions was calculated by averaging the scores of 5 dimensions. EQ-5D final score ranges from 1-3." (NCT01328379)
Timeframe: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Interventionunits on a scale (Mean)
Placebo-0.07
Dalfampridine-ER 5mg-0.05
Dalfampridine-ER 10mg-0.07

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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).

"The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability.~A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study." (NCT01328379)
Timeframe: Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4)

Interventionfeet per second (Mean)
Placebo0.301
Dalfampridine-ER 5mg0.296
Dalfampridine-ER 10mg0.391

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Dalfampridine Effect on Quality of Life Change From Baseline.

Dalfampridine treatment will result in change in quality of life. The National Eye Institute Visual Function Questionnaire consists of 25 questions characterizing visual function at home and in the community. Score ranges from 100 (best) to 0 (worst). (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

InterventionNEI VFQ percentage (Median)
Dalfampridine0
Placebo0

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Visual Evoked Potential P100 Latency Per Treatment Arm

Visual evoked potential 60min P100 latency on dalfampridine vs. placebo. (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Interventionmilliseconds (Mean)
Dalfampridine121.6
Placebo120.2

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Percentage of Eyes That Improved by One-line (5 Letters)

Percentage of eyes that improved by one-line (5 letters) on the 5% contrast sensitivity chart (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

InterventionPercent of Eyes (Number)
Dalfampridine11.1
Placebo15.3
Both37.5
Neither36.1

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Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Change in the number of letters able to read while on Dalfampridine and Placebo relative to their baseline scores. (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Interventionletters (Mean)
Dalfampridine3
Placebo2.5

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Percentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart

(NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

InterventionPercentages of eyes that improved (Number)
Dalfampridine9.7
Placebo11.1
Both11.1
None68.1

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Changes in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).

Dalfampridine will change color vision Total Error Scores from baseline on the Farnsworth Munsell 100 Hue Sort Test. Farnsworth Munsell 100 Hue Test requires placing 100 color palettes in the correct order based upon color hue. Scores are determined by the frequency and severity of any displacement in the correct order. One error equates to one misplaced hue, by one step or position. An error score greater than 500 indicates virtually no color discrimination. An error score of 0 indicates no errors in ordering the hues. A Total Error Score of 0 to 128 could be seen in a normal population. (NCT01337986)
Timeframe: Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - postintervention 1) and Visit 3 (Week 8 - post intervention 2)

InterventionFM100 Total Error Score (Mean)
Dalfampridine-13.0
Placebo-10.6

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Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores

Per Protocol Analysis to assess differences in EDTRS 5% Contrast Sensitivity (LogMAR) Scores at visits 2 and 3 Relative to Visit 1 on patients taking Dalfampridine vs Placebo. (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

InterventionLogMAR Score (Mean)
Group B: Dalfampridine-0.04
Group B: Placebo-0.06
Group A: Placebo-0.08
Group A: Dalfampridine-0.06

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Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

Per Protocol Analysis to assess difference in number of letters on the EDTRS 5% Contrast Sensitivity (LogMAR) Chart scores at visits 2 and 3 Relative to Visit 1 (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Interventionletters (Mean)
Group B: Dalfampridine2
Group B: Placebo2
Group A: Placebo4
Group A: Dalfampridine3

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Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1

Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1 on Dalfampridine vs Placebo. Pelli-Robson is scored based upon the numbers read on the chart converted to LogMAR units. The scale is 0.00 (worst) to 2.35 (best). (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Interventionunits on a scale (Mean)
Dalfampridine0.07
Placebo0.06

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Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1

Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Improvement from baseline scores. (NCT01337986)
Timeframe: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Intervention5% Contrast LogMAR Score (Mean)
Dalfampridine0.06
Placebo0.05

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Odds Ratio Quartile of Visual Field Index

"The Visual Field Index (VFI) is a global index that assigns a number between 1% to 100% based on an aggregate percentage of visual function, with 100% being a perfect age-adjusted visual field.~Probability of falling in the best quartile for visual field (VFI) measures (Q1), relative to the three next quartiles for worse VFIs (Q2-4), while on Dalfampridine vs Placebo. Due to the clustered observations at different times in a cross-over design, the visual field data is not suited to a normal theory model and should not be expressed as a continuous variable. Thus, a categorical model that uses a multinomial distribution for measurement of 4 categories was selected for proper statistical modeling, with results expressed as odds ratios." (NCT01337986)
Timeframe: Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - post intervention 1) and Visit 3 (Week 8 - post intervention 2)

,
InterventionVisual Field Index % of normal vision (Mean)
Baseline (Visit 1)Post Intervention 1 (Visit 2)Post Intervention 2 (Visit 3)
Dalfampridine Then Placebo77.5378.5079.71
Placebo Then Dalfampridine85.3886.6586.00

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Stepcount

change in daily stepcount recorded by an accelerometer and averaged over 1 week of wear baseline vs 4 weeks (NCT01356940)
Timeframe: 10 weeks

Interventionsteps per day (Least Squares Mean)
Dalfampridine ER vs Baseline148.7
Placebo vs Baseline128

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Peak Activity Index

peak activity index is a measure of the 30 fastest minutes of walking over a 24 hour period, averaged over one week of accelerometer wear. Measurement is change from baseline to 4 weeks on intervention (NCT01356940)
Timeframe: 10 weeks

Interventionchange in strides per minute (Mean)
Dalfampridine ER 10mg Bid0.6
Placebo0.3

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Change in Automatic Postural Response (APR )Latency

Automatic Postural Response (APR) latencies will be measured by Computerized Dynamic Posturography (CDP). The restoration of balance after an unexpected movement by Computerized Dynamic Posturography relies on automated postural responses in the upper and lower legs, trunk, shoulders, and neck muscles. APR latency is the reaction- time response to movements of the support surface on which the subject stands. These responses typically occur at onset latencies of ~100 milliseconds. In response to a change, both feet-in-place and stepping strategies can be used to recover balance, with the incidence of stepping responses becoming larger as the change magnitude increases voluntary movements in human subjects. (NCT01444300)
Timeframe: Baseline to 12 weeks

Interventionmilliseconds (Mean)
Dalfampridine5.71
Placebo4.58

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Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores

The ABC is an 11-point scale and subjects are asked to indicate personal level of confidence in doing specific activities without losing balance or becoming unsteady on a scale from 0% to 100%. The ratings are added (possible range =0 -1600) and divide by 16 to get each subject's ABC score. A high ABC score indicates a high degree of confidence and a low ABC score indicates a low degree of confidence. (NCT01444300)
Timeframe: Baseline to 12 weeks

InterventionScores on a scale (Mean)
Dalfampridine1.30
Placebo0.41

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Change in Timed 25 Foot Walking Speed

(NCT01444300)
Timeframe: Baseline to 12 weeks

Interventionseconds (Mean)
Dalfampridine0.26
Placebo0.39

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Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP)

"Safety and tolerability will be assessed primarily by monitoring Treatment Emergent Adverse Events (TEAEs)~TEAEs are defined as Adverse Events (AEs) with date of onset (or worsening) on or after the start-date of double-blind treatment and no more than 5 days after the last dose of double-blind treatment for Part A of the study and no more than 9 days for Part B of the study.~The severity categories of mild, moderate or severe, are defined below:~Mild is defined as causing no limitation of usual activities~Moderate is defined as causing some limitation of usual activities~Severe is defined as causing inability to carry out usual activities" (NCT01468350)
Timeframe: up to 31 days

,,,
Interventionparticipants (Number)
TEAEsSerious TEAEsTEAEs Maximum Severity - MildTEAEs Maximum Severity - ModerateTEAEs Maximum Severity - SevereTEAEs Possibly Related to Study DrugTEAEs Leading to Withdrawal of Study Drug
PART A: Dalfampridine-ER 10mg2020000
PART A: Placebo1010010
PART B: Dalfampridine-ER 10mg9081070
PART B: Placebo6051030

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Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects. (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-0.4-0.20.2-1.1-0.5
Responder3.34.03.33.02.8

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Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders

EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS0.050.050.050.040.05
Progressive-Relapsing MS0.070.060.090.020.10
Relapsing-Remitting MS0.050.070.040.050.04
Secondary-Progressive MS0.040.060.050.020.03

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Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders

EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS6.77.36.07.95.5
Progressive-Relapsing MS4.74.64.15.54.5
Relapsing-Remitting MS8.810.18.08.28.8
Secondary-Progressive MS6.58.26.15.66.1

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Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented. (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

Interventionunits on a scale (Least Squares Mean)
Month 3Month 6Month 9Month 12
Responder4.23.43.22.9

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Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above. (NCT01480076)
Timeframe: From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose)

,,
Interventionparticipants (Number)
AESAESevere AEStudy treatment related AEStudy treatment related SAEDeathAE leading to study drug discontinuationAE leading to study discontinuation
All Participants5867950285724019
Non-responder6432370081
Responder5227648248723218

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Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-0.6-1.2-0.8-0.70.2
Non-responder: Taking Additional MS Therapy-0.30.10.6-1.2-0.8
Responder: Not Taking Additional MS Therapy3.94.13.94.03.6
Responder: Taking Additional MS Therapy3.14.03.12.72.5

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Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS2.53.12.33.01.7
Progressive-Relapsing MS3.22.73.93.22.9
Relapsing-Remitting MS4.55.54.44.24.0
Secondary-Progressive MS3.84.53.93.23.4

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Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12

The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-2.1-2.1-3.0-0.3-2.8
Responder-10.3-13.0-10.6-8.9-8.6

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Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders

The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-8.3-9.1-8.7-8.2-7.4
Progressive-Relapsing MS-7.5-8.6-7.9-8.3-5.1
Relapsing-Remitting MS-9.4-11.2-8.8-8.3-9.3
Secondary-Progressive MS-6.5-8.9-6.8-5.1-5.3

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Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-3.2-4.0-5.20.5-4.3
Non-responder: Taking Additional MS Therapy-1.5-1.4-2.2-0.4-2.1
Responder: Not Taking Additional MS Therapy-12.2-14.0-12.2-11.8-11.1
Responder: Taking Additional MS Therapy-9.6-12.6-10.0-8.0-7.8

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Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders

The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-8.3-10.6-8.4-7.9-6.2
Progressive-Relapsing MS-12.5-12.6-14.9-10.4-11.9
Relapsing-Remitting MS-12.1-15.0-12.0-10.5-10.9
Secondary-Progressive MS-10.3-13.3-10.9-8.9-8.2

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Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy0.61.11.50.0-0.3
Non-responder: Taking Additional MS Therapy-0.1-1.30.21.3-0.7
Responder: Not Taking Additional MS Therapy3.94.84.12.83.9
Responder: Taking Additional MS Therapy2.84.03.02.12.1

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Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS3.23.93.52.72.5
Progressive-Relapsing MS2.02.62.92.00.5
Relapsing-Remitting MS4.04.94.33.13.5
Secondary-Progressive MS3.04.52.92.12.6

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Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder0.1-0.60.61.0-0.6
Responder3.14.23.32.32.5

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Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy0.02-0.020.030.020.04
Non-responder: Taking Additional MS Therapy-0.000.02-0.00-0.00-0.03
Responder: Not Taking Additional MS Therapy0.060.070.050.060.07
Responder: Taking Additional MS Therapy0.040.070.050.030.03

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Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12

EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder0.000.010.010.01-0.01
Responder0.050.070.050.040.04

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Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-0.8-1.21.5-1.8-1.5
Non-responder: Taking Additional MS Therapy-5.8-3.9-5.6-6.1-7.7
Responder: Not Taking Additional MS Therapy8.68.68.68.78.7
Responder: Taking Additional MS Therapy6.07.65.25.55.5

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Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders

The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-0.5-1.6-0.8-0.30.7
Progressive-Relapsing MS-1.7-1.9-1.6-2.0-1.2
Relapsing-Remitting MS-2.5-3.2-2.3-2.4-2.0
Secondary-Progressive MS-1.1-2.1-1.3-0.7-0.5

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Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy0.8-0.01.31.11.0
Non-responder: Taking Additional MS Therapy0.8-0.50.62.01.1
Responder: Not Taking Additional MS Therapy-1.9-2.9-2.1-1.6-1.0
Responder: Taking Additional MS Therapy-1.3-2.1-1.2-1.1-0.7

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Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12

The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder0.8-0.40.81.81.1
Responder-1.4-2.3-1.4-1.2-0.8

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Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionpercentage of activity impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-4.1-3.1-4.7-4.1-4.4
Responder-11.4-13.5-12.3-10.4-9.2

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Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of activity impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-3.1-1.8-0.51.6-11.6
Non-responder: Taking Additional MS Therapy-4.2-3.4-6.3-5.9-1.3
Responder: Not Taking Additional MS Therapy-13.3-15.7-14.6-12.0-10.9
Responder: Taking Additional MS Therapy-10.6-12.7-11.5-9.8-8.5

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Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of activity impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-7.1-8.7-9.0-7.1-3.7
Progressive-Relapsing MS-12.2-11.0-14.2-10.8-13.0
Relapsing-Remitting MS-14.9-16.2-15.1-14.9-13.5
Secondary-Progressive MS-9.8-13.4-11.1-7.5-7.1

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Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionpercentage of work time missed (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-8.3-4.0-7.6-9.6-12.1
Responder-2.5-3.0-5.3-1.1-0.7

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Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of work time missed (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy14.928.66.413.910.6
Non-responder: Taking Additional MS Therapy-11.9-8.3-10.3-12.8-16.2
Responder: Not Taking Additional MS Therapy-2.4-2.0-4.3-2.1-1.1
Responder: Taking Additional MS Therapy-3.0-3.7-6.0-1.2-1.0

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Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of work time missed (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-2.5-3.3-3.3-1.1-2.2
Progressive-Relapsing MS-4.0-1.1-2.3-10.0-2.7
Relapsing-Remitting MS-2.9-3.1-6.4-1.9-0.3
Secondary-Progressive MS-1.5-2.6-5.32.0-0.1

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Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of overall work impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy1.218.0-8.23.7-8.6
Non-responder: Taking Additional MS Therapy-9.9-6.6-1.8-18.5-12.6
Responder: Not Taking Additional MS Therapy-6.7-7.1-7.7-5.5-6.5
Responder: Taking Additional MS Therapy-4.8-7.9-7.8-1.6-1.8

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Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of overall work impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS-0.8-1.7-3.31.20.4
Progressive-Relapsing MS-6.52.9-6.5-9.7-12.6
Relapsing-Remitting MS-7.5-10.7-9.2-4.9-5.3
Secondary-Progressive MS-6.8-10.4-11.9-2.6-2.1

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Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionpercentage of impairment while working (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-8.4-1.8-5.6-17.9-8.4
Responder-4.2-6.9-6.5-3.0-0.3

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Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of impairment while working (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-11.5-3.3-15.9-6.0-20.7
Non-responder: Taking Additional MS Therapy-7.3-1.0-3.8-19.0-5.5
Responder: Not Taking Additional MS Therapy-6.4-8.1-8.0-5.6-3.8
Responder: Taking Additional MS Therapy-3.1-6.1-5.6-1.91.1

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Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, and 12

,,,
Interventionpercentage of impairment while working (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Primary-Progressive MS0.8-1.7-2.50.56.8
Progressive-Relapsing MS-7.3-2.9-8.3-4.9-13.1
Relapsing-Remitting MS-5.8-8.6-6.7-5.0-2.9
Secondary-Progressive MS-4.2-8.0-8.7-1.81.4

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Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy

The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Months 3, 6, 9, and 12

,,,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder: Not Taking Additional MS Therapy-2.8-1.0-2.6-2.4-5.1
Non-responder: Taking Additional MS Therapy-0.30.2-2.6-0.21.3
Responder: Not Taking Additional MS Therapy-9.7-11.1-9.5-8.9-9.1
Responder: Taking Additional MS Therapy-7.1-9.0-7.1-6.1-6.2

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Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12

The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionunits on a scale (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-1.0-0.2-2.6-0.8-0.5
Responder-7.8-9.6-7.7-6.8-7.0

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Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12

WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). (NCT01480076)
Timeframe: Baseline, Months 3, 6, 9, 12

,
Interventionpercentage of overall work impairment (Least Squares Mean)
OverallMonth 3Month 6Month 9Month 12
Non-responder-8.7-4.5-2.9-15.9-11.7
Responder-5.2-7.7-7.8-2.4-2.9

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Timed 25-foot Walk Test (T25FW)

time required to perform T25FW. (NCT01491022)
Timeframe: 4 weeks

Interventionseconds (Mean)
Ampyra Then Placebo11.6
Placebo Then Ampyra11.8

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Freezing of Gait Questionnaire (FOGQ)

change in FOGQ score 0- 16, where 0 is normal, 16 is severely impaired (NCT01491022)
Timeframe: 4 weeks

Interventionunits on a scale (Mean)
Ampyra Then Placebo13.16
Placebo Then Ampyra13.4

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Change in Velocity

The primary outcome measure will be the change in gait velocity as measured with by 3-dimensional gait analysis system. (NCT01491022)
Timeframe: baseline and 4 weeks

Interventionm/s (Mean)
Ampyra0.03
Placebo0.05

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Change in Stride Legth

change in stride length as measured by 3 D capture analysis (NCT01491022)
Timeframe: 4 weeks

Interventionmeters (Mean)
Ampyra-0.01
Placebo0.05

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United Parkinson's Disease Rating Scale Score(UPDRS) ,

change in UPDRS score (motor) range 0-104, where 0 is good and 104 is worse. (NCT01491022)
Timeframe: 4 weeks

Interventionunits on a scale (Mean)
Ampyra35.22
Placebo35.55

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Timed Up and Go (TUG) Score

time required to perform TUG. (NCT01491022)
Timeframe: 4 weeks

Interventionseconds (Mean)
Ampyra Then Placebo23.25
Placebo Then Ampyra20.6

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Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg

The BBS is a 14-item scale that evaluates subjects ability to sit, stand, reach, maintain single-leg stance, and turn. The scoring is rated from 0 (cannot perform task) to 4 (normal performance of task) for each of 14 items. The maximum possible score is 56 and the lowest 0. A higher total score is indicative of better performance. (NCT01535664)
Timeframe: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)

Interventionunits on a scale (Mean)
Dalfampridine-ER Withdrawn45.7
Dalfampridine-ER 10mg47.3

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Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg

"The T25FW test is a measure of ambulatory function that provides quantitative data and is used widely in the MS population~A higher walking speed is indicative of better performance" (NCT01535664)
Timeframe: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)

InterventionFeet per second (ft/s) (Mean)
Dalfampridine-ER Withdrawn3.42
Dalfampridine-ER 10mg3.78

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Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg

"Subjects will walk without assistance for 2 minutes and the distance will be measured and timed by the use of a stop watch.~A larger walking distance is indicative of better performance." (NCT01535664)
Timeframe: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)

InterventionMeters (Mean)
Dalfampridine-ER Withdrawn119.381
Dalfampridine-ER 10mg129.044

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Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg

"The co-primary efficacy variable was overall balance. This novel composite score was created from standardized individual NeuroCom test results (Z-scores).~Overall balance is a weighted average of Sensory Organization Test (SOT) fixed surface eyes open, fixed surface eyes closed, walls moving eyes open, surface moving eyes open, surface moving eyes closed, surface and walls moving eyes open; Limits of Stability Test (LOS) measuring reaction time, movement velocity, endpoint excursion, maximum excursion and directional control; and Adaptation Test (ADT) measuring the averaged, raw sway and center of force during rotational disturbances. ZBAL (Z-Score Balance)= (ZSOT*0.5) + (ZADT*0.2) + (ZLOS*0.3)~Overall balance was calculated by transforming ZBAL into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance." (NCT01535664)
Timeframe: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)

Interventionunits on a scale (Mean)
Dalfampridine-ER Withdrawn55.10
Dalfampridine-ER 10mg54.98

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Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg

"The co-primary efficacy variable was overall gait. This novel composite score was created from standardized individual NeuroCom test results (Z-scores).~ZGAIT (Z-Score Gait) is the average of Walk Across (WA) measuring step width, step length, speed; Tandem Walk (TW) measuring step width, speed and end sway, and Step/Quick turn (SQT) measuring turn time and turn sway).~Overall gait was calculated by transforming ZGAIT into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance." (NCT01535664)
Timeframe: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)

Interventionunits on a scale (Mean)
Dalfampridine-ER Withdrawn46.01
Dalfampridine-ER 10 mg51.40

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Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs)

"A TEAE is defined as any adverse event with date of onset (or worsening) on or after the start-date of double-blind treatment through 7 days after the last dose of double-blind treatment.~The severity categories of mild, moderate or severe, are defined below:~Mild is defined as causing no limitation of usual activities~Moderate is defined as causing some limitation of usual activities~Severe is defined as causing inability to carry out usual activities" (NCT01605825)
Timeframe: up to 36 days

,
Interventionparticipants (Number)
Subjects with any TEAEsTEAEs Possibly Related to study drugTEAEs Maximum Severity - MildTEAEs Maximum Severity - ModerateTEAEs Maximum Severity - SevereTEAEs leading to withdrawal of study drugTEAEs SeriousSubjects who died
Dalfampridine-ER422429103520
Placebo301616131120

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Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores

"The Spasm Frequency score is the average rating by the clinician of the left and right arm(s) and leg(s), each evaluated on a 4-point scale (from 0=no spasms to 4=spontaneous spasms occurring more than ten times per hour), with higher scores denoting a greater degree of muscle spasms.~The Spasm Severity score is the average rating of the left and right arm(s) and leg(s), each evaluated on a three-point scale (mild, moderate, or severe) as rated by the clinician on the basis of patient self-report.~On both, a negative change in score signifies improvement in muscle spasms. The average Spasm Frequency/Spasm Severity Score was calculated as the average of the left and right non-missing scores." (NCT01683838)
Timeframe: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

,
Interventionunits on a scale (Mean)
Arm Spasm FrequencyLeg Spasm FrequencyArm Spasm SeverityLeg Spasm Severity
Fampridine-SR 50mg/Day-0.13-0.12-0.09-0.14
Placebo0.02-0.10-0.02-0.07

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Adjusted Mean Change in Subject Bowel Function Diary Scores

"Bowel questions pertaining to the average number of minutes per day spent on bowel routine were asked of all patients daily.~A negative change in patient bowel function diary score signifies improvement." (NCT01683838)
Timeframe: Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

Interventionminutes (Mean)
Fampridine-SR 50mg/Day-0.7
Placebo0.3

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Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity

"The Ashworth evaluates the functioning of two lower extremity muscle groups, the hamstring and quadriceps muscles, while in the supine position. The test measures extension of the right and left hamstring muscle and flexion of the right and left quadriceps muscle using the following 5-point grading scale:~1=no increased tone; 2=slight increase in tone, giving a catch when the affected part is moved in flexion or extension; 3=more marked increase in tone, but affected part is easily flexed; 4=considerable increase in tone, passive movement is difficult; 5=affected part is rigid in flexion and extension.~The Ashworth Score was determined by adding all individual scores for each muscle group and dividing by four. Higher Ashworth Scores indicated greater spasticity." (NCT01683838)
Timeframe: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day-0.28
Placebo-0.16

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Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores

The supervising clinician rated the patient's neurological condition following treatment as compared to the screening visit on a seven-point scale (from 1=very much improved to 7=very much worse). The assessment was based on the clinician's overall impression of the patient's neurological status (specifically bowel, bladder, and sexual function; spasticity; and other neurological functions) and general state of health related to his or her participation in the study. Negative change scores indicated a change for the better. (NCT01683838)
Timeframe: Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98)

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day-0.2
Placebo-0.2

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Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores

"The SGI is a 7-unit ordinal scale used by the subject to evaluate the effects of study medication on his/her quality of life during the preceding week, with higher scores denoting greater satisfaction. A positive change score in SGI signifies improved outcome.~The questionnaire consisted of one question (How do you feel about the effects of the investigational drug over the past 7 days?). The answer was based on a numerical rating scale where 1=terrible; 2=unhappy; 3=mostly dissatisfied; 4=neutral/mixed; 5=mostly satisfied; 6=pleased; 7=delighted." (NCT01683838)
Timeframe: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day-0.0
Placebo0.1

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Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score

Ten key muscle groups for the right and left sides were rated on a 0 (absent) to 5 (normal) scale, with a possible total score of 100. Higher positive change scores indicate improved motor function. (NCT01683838)
Timeframe: Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98

Interventionunits on a scale (Mean)
Fampridine-SR 50mg/Day0.4
Placebo0.7

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Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores

"Bowel/bladder questions pertaining to the average number of times per day the patient experienced accidental urination/leakage and the average number of bowel movements per day were asked of all patients daily.~A negative change in patient bladder/bowel function diary score signifies improvement." (NCT01683838)
Timeframe: Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

,
Interventionepisodes (Mean)
Number of Accidental Urination or LeakageNumber of Bowel Movements
Fampridine-SR 50mg/Day-0.20.1
Placebo-0.2-0.0

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Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores

"The FSFI is a brief, reliable, and valid self-administered questionnaire of 19 questions (items). It contains six domains: Desire (2 items score range: 1 Very low or none at all to 5 Very high), Arousal (4 items score range: 0 No sexual activity to 5 Almost always or always), Lubrication (4 items score range: 0 No sexual activity to 5 Almost always or always), Orgasm (3 items score range: 0 No sexual activity to 5 Almost always or always), Satisfaction (3 items score range: 0 No sexual activity to 5 Very satisfied) and Pain (3 items score range: 0 Did not attempt intercourse to 5 Almost never or never).~A positive change signifies improvement." (NCT01683838)
Timeframe: Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98

,
Interventionunits on a scale (Mean)
DesireArousalLubricationOrgasmSatisfaction (Fampridine-SR N=13, Placebo N=12)Pain
Fampridine-SR 50mg/Day0.70.60.70.20.40.7
Placebo0.20.2-0.20.40.3-0.1

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Change From Baseline in Mean International Index of Erectile Function (IIEF) Score

"Male patients were asked to complete the IIEF questionnaire on sexual function. The IIEF is a brief, reliable, and valid self-administered questionnaire of 15 questions (items) that were categorized into five domains: Erectile Function (EF) scores: 0-6 Severe dysfunction, 7-12 Moderate dysfunction, 13-18 Mild to moderate dysfunction, 19-24 Mild dysfunction, 25-30 No dysfunction. Orgasmic Function (OF) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Sexual Desire (SD) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Intercourse Satisfaction (IS) score range: 0-3 Severe dysfunction to 13-15 No dysfunction, and Overall Satisfaction (OS) score range: 0-2 Severe dysfunction to 9-10 No dysfunction.~Domain scores were derived by summing the individual items within a given domain. Final scale ranges from 0 (negative) to 5 (positive). A positive change in IIEF domain scores signifies improvement." (NCT01683838)
Timeframe: Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98

,
Interventionunits on a scale (Mean)
EF (Fampridine-SR Number (N) =65, Placebo N=77)OF (Fampridine-SR N=64, Placebo N=76)SD (Fampridine-SR N=64, Placebo N=75)IS (Fampridine-SR N=64, N=76)OS (Fampridine-SR N=51, Placebo N=66)
Fampridine-SR 50mg/Day0.80.3-0.00.40.4
Placebo1.60.00.00.40.3

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Change in Timed 25 Feet Walking Test (T25FW)

The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time, in seconds, is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention. (NCT01811706)
Timeframe: Baseline and 4 weeks after Dalfampridine or placebo

,
Interventionsecond (Mean)
T25FW at baselineChange from baseline at 4 weeks
Dalfampridine23.7-1.1
Placebo24.4-0.3

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Change in Scale of Assessment and Rating of Ataxia (SARA)

Scale for the assessment and rating of ataxia (SARA) is a clinical scale that is based on a semiquantitative assessment of cerebellar ataxia on an impairment level. SARA has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. SARA score ranges from 0 to 40, with higher scores indicating more severe disease. (NCT01811706)
Timeframe: Baseline and 4 weeks after Dalfampridine or placebo

,
Interventionpoint (Mean)
SARA at baselineChange from baseline at week 4
Dalfampridine10.00.6
Placebo10.10.8

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Biomechanical Assessment of Gait (BAG)-Stride Length

Biomechanical Assessment of Gait is a sensitive, quantitative movement analysis system. Stride length was analyzed. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention. (NCT01811706)
Timeframe: Baseline and 4 weeks after Dalfampridine or placebo

,
Interventioncm (Mean)
Sstride Length at baselineStride Length at week 4
Dalfampridine112.71.6
Placebo111.84.0

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Symbol Digit Modalities Test

The Symbol Digit Modalities Test is a measure of cognitive processing speed. The outcome is the total number of correct digit substitutions in 90 seconds, with a possible total range of 0-120. Higher values reflect a better score/outcome than lower scores. (NCT02006160)
Timeframe: Week 0, Week 12

,
Interventionscore on a scale (Mean)
Week 0Week 12
Control35.0638.63
Treatment41.1845.05

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Upper and Lower Extremity Muscle Strength Measurements

Upper and lower extremity muscle strength measurements, using a hand held dynamometer, at the beginning and end of each arm. Change in muscle strength between baseline and end (8 weeks) of each intervention are provided. (NCT02166346)
Timeframe: baseline and end (8 weeks) of each intervention

,
InterventionPounds (Mean)
Supine Left Hip FlexorSupine Right Hip FlexorProne Left Hip FlexorProne Right Hip FlexorLeft GripRight Grip
Dalfampridine.64202.57743.2863.97523.1594-1.3602
Placebo-0.051872.854-1.497-4.4162-2.90072.1665

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Walking Speed During Timed 25-foot Walk

In this cross-over study, walking speed was recorded 4 times for each subject while in both the dalfampridine and placebo arms. The results average all of the times while on damfampridine and compares them to the average of the times while on placebo. (NCT02166346)
Timeframe: Every 2 weeks during each 8 week intervention

,
Interventionfeet/second (Mean)
Change from baseline to 2 weeksChange from baseline to 4 weeksChange from baseline to 6 weeksChange from baseline to 8 weeks
Dalfampridine0.33420.45930.54450.3803
Placebo0.47450.17430.56970.2101

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Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.

AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged. (NCT02208050)
Timeframe: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

Interventionunits on a scale (Mean)
Fampridine35.4
Placebo38.4

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Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)

"Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test on treatment (assessments 4 & 5 or 7 & 8) compared with baseline assessments (assessments 1,2 & 3).~Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.~Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period" (NCT02208050)
Timeframe: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8

InterventionParticipants (Count of Participants)
Dominant hand71962151Dominant hand71962150Non-dominant hand71962150Non-dominant hand71962151
RespondersNon-responders
Placebo0
Placebo61
Fampridine3
Fampridine60

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Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)

"9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two on treatment 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 & 5 or 7 & 8) improving 20% from the average of the baseline assessments (1, 2 & 3). Washout assessment not included in the analysis." (NCT02208050)
Timeframe: 20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period.

InterventionParticipants (Count of Participants)
Dominant hand71962148Dominant hand71962149Non-dominant hand71962148Non-dominant hand71962149
RespondersNon-responders
PR-Fampridine4
Placebo3
PR-Fampridine58
Placebo59
PR-Fampridine2
Placebo1
PR-Fampridine60
Placebo61

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The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)

"A mobility responder to Fampridine will be defined as a patient with both of the two on treatment T25FW assessments (assessments 4 & 5 or 7 & 8) being better (shorter time in seconds) than the maximum of any of the four off treatment assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.~Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period." (NCT02208050)
Timeframe: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8

,
InterventionParticipants (Count of Participants)
RespondersNon-responders
Fampridine592
Placebo592

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Mean Scores of MSIS-29 - Fampridine and Placebo

MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged. (NCT02208050)
Timeframe: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

Interventionunits on a scale (Mean)
Fampridine: MSIS-2042.4
Placebo: MSIS2043.3
Fampridine: MSIS-930.5
Placebo: MSIS-929.4

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Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.

Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged. (NCT02208050)
Timeframe: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

Interventionunits on a scale (Mean)
On Treatment: Fampridine64.5
Placebo65

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Mean Scores in DASH - Fampridine and Placebo.

"Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.~DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged." (NCT02208050)
Timeframe: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

InterventionMean units on a scale. (Mean)
Fampridine35.4
Placebo38.3

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Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks

"The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 (no impact of MS) to 100 (extreme impact of MS); a negative change indicates an improvement in function.~Data are based on a mixed model for repeated measures (MMRM) model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline MSIS-29 physical score and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the mean over screening and Day 1." (NCT02219932)
Timeframe: Baseline to Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo-4.68
Fampridine 10 mg BID-8.00

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Proportion of Participants Achieving a Mean Improvement of ≥ 8 Points From Baseline on the Multiple Sclerosis Walking Scale (MSWS-12) Over 24 Weeks

"MSWS-12 is a participant self-assessment of the walking limitations due to MS during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where higher scores indicate greater impact on walking.~A responder is defined as a participant with a mean improvement of at least 8 points over 24 weeks compared to baseline. Baseline is defined as the mean at Screening and Day 1 visits. If a participant has a mean MSWS-12 score of < 0.5 over the double-blind period, and a baseline MSWS-12 score of < 8 points, the participant is counted as a responder. A participant who indicates they cannot walk at all on MSWS-12 during any double-blind visit, and who shows severe disability and an inability to walk on other efficacy assessments is counted as a non-responder. Estimated proportion obtained from binomial proportions." (NCT02219932)
Timeframe: Baseline to 24 weeks

Interventionproportion of participants (Number)
Placebo0.336
Fampridine 10 mg BID0.432

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Change From Baseline in ABILHAND Score Over 24 Weeks

"The ABILHAND Questionnaire measures a participant's perceived difficulty in performing everyday manual activities in the last 3 months. The participant completes a 56-item questionnaire by estimating their own difficulty or ease in performing each of 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 (poor manual ability) to 100 (good manual ability); a positive change indicates an improvement in manual ability.~Data are based on an MMRM model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline ABILHAND and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the Day 1 assessment." (NCT02219932)
Timeframe: Baseline to Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo0.75
Fampridine 10 mg BID1.49

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Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks

"The BBS is a widely used assessment tool to identify balance impairment. Functional activities such as reaching, bending, transferring, and standing are evaluated on the test to evaluate balance. Participants are asked to complete 14 tasks that are rated from 0 (cannot perform) to 4 (normal performance) for a total of 56 points. BBS scores range from 0 (poor balance) to 56 (good balance); a positive change indicates improvement.~Data are based on an MMRM model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline BBS and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the mean over screening and Day 1." (NCT02219932)
Timeframe: Baseline to Week 24

Interventionunits on a scale (Least Squares Mean)
Placebo1.34
Fampridine 10 mg BID1.75

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Proportion of Participants Achieving a Mean Improvement From Baseline of ≥ 15% in Timed Up and Go (TUG) Speed Over 24 Weeks

"TUG is a timed walking test designed to measure gait performance and balance. It measures in seconds the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm [18in], arm height 65 cm [25.6 in]), walk a distance of 3 meters (118 inches, approximately 10 feet), turn, walk back to the chair, and sit down.~A responder is defined as a participant with a mean improvement of at least 15% in TUG speed over 24 weeks compared to baseline. Baseline is defined as the mean at Screening and Day 1 visits. Estimated proportion obtained from binomial proportions. There are 2 TUG tests given, and the average across the 2 tests is used to calculate average speed. Healthy participants below the age of 79 are expected to complete this task in 7-10 seconds (American College of Rheumatology). Missing data are handled using multiple imputation and baseline is defined as the mean over Screening and Day 1." (NCT02219932)
Timeframe: Baseline to Week 24

Interventionproportion of participants (Number)
Placebo0.347
Fampridine 10 mg BID0.434

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Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary)

"The Walk-12 is a 12-question questionnaire that asks subjects to rate limitations of their mobility during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). For each visit, the Walk-12 score will be calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. A higher score indicates a greater degree of limitation in walking. A negative change indicates an improvement in walking. 0 = no limitation in mobility to 100 extreme limitation in mobility.~Walk-12 Score = 100 * [(Mean of the 12 items) - 1]/(5-1)" (NCT02271217)
Timeframe: Baseline, week 12

Interventionunits on a scale (Mean)
Placebo45.40
Dalfampridine-ER 7.5 mg48.34
Dalfampridine-ER 10mg49.26

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Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12

"The 2MinWT measures the distance a subject can walk in 2 minutes. Participants showing at Least a 20% Improvement on the 2MinWT at 12-weeks are considered Responders." (NCT02271217)
Timeframe: Week 12

,,
Interventionparticipants (Number)
ResponderNon-ResponderMissing
Dalfampridine-ER 10mg23908
Dalfampridine-ER 7.5 mg17968
Placebo179712

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Improved Physical Capacity

The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. The first levels 1.0 to 4.5 refers to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refers to the loss of ambulatory ability. It also provides eight subscale measurements called Functional System (FS) scores. The levels of function within each category refer to the eight FS affected by MS: The FS are scored on a scale of 0 (low level of problems) to 5 (high level of problems) to best reflect the level of disability observed clinically. (NCT02280096)
Timeframe: 15-20 minutes

Interventionscore on a scale (Mean)
4-aminopyridine Treatment4.6
Placebo4.04

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Tower Of London (TOL). Total Moves and Total Correct Moves

Measures higher order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Correct Moves and Total Moves. Total moves: higher scores indicate a worse cognitive performance (min= 0, max=58+); Total correct higher scores indicate a better cognitive performance (min=0, max=10). (NCT02280096)
Timeframe: 25-30 minutes

,
Interventionscore on a scale (Mean)
Total movesCorrect moves
4-aminopyridine42.74
Placebo50.83

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Tower Of London (TOL). Execution Time and Problem-solving Time

Measures higher-order problem-solving ability. The information it provides is not only useful when assessing frontal lobe damage, but also when evaluating attention disorders and executive functioning difficulties. The administrator arranges red, green, and blue beads on a peg board to match the configuration in the diagram. The patient is asked to replicate the configuration on a second peg board. Scores are calculated for Total Execution Time (since the patient performs the first move until he ends the test), Total Problem-Solving Time (the sum of planning and execution times). Total execution time higher scores indicate a worse outcome (min= 0-78, max=564+ seconds), Total problem-solving time higher scores indicate a worse outcome (min= 0-56, max=500+ seconds). (NCT02280096)
Timeframe: 25-30 minutes

,
Interventionseconds (Mean)
Total execution timeTotal problem-solving time
4-aminopyridine296.2363.3
Placebo367.9426.8

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Number of Participants With Abnormal Studies

Safety surveillance will be done every two weeks from the beginning of the study, intentionally searching for adverse events (AE). EEG (Diffuse or focal cerebral dysfunction through demonstration of background slowing or presence of epileptiform activity assessed by a neurophysiologist) and laboratory tests (Presence of values higher of the normal value established by local laboratory and related to the administration of treatments), blood and urine samples: creatinine, blood urea nitrogen, total cholesterol, triglycerides, total direct, and indirect bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase, lactic acid dehydrogenase, amylase and lipase. A complete blood cell count with differentials and a routine urinalysis and urine culture also obtained at each visit, will be done before the patients take 40, 50 and 60 mg/day. The number of participants with abnormal studies were reported. (NCT02280096)
Timeframe: 22 weeks

,
InterventionParticipants (Count of Participants)
Number of participants with abnormal lab resultsNumber of participants with abnormal EEG
4-aminopyridine Treatment10
Placebo00

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Wisconsin Card Sorting Test (WCST)

"Is used primarily to assess perseveration and abstract thinking, allows the clinician to assess the following 'frontal' lobe functions: strategic planning, organised searching, utilising environmental feedback to shift cognitive sets, directing behaviour toward achieving a goal. WCST measures abstract reasoning and ability to alter problem solving strategies. Patients are given 128 response cards and 4 stimulus cards and asked to match each stimulus card to 1 pile of response cards. The patient is not told how to match the cards, only right or wrong to each placement. The examiner may change matching rules during the test. Perseveration errors occur when subject repeats the same error no matter how many times they are told the placement is wrong. Higher scores indicate a worse cognitive performance (min=0-3, max=58-126)" (NCT02280096)
Timeframe: 10-15 minutes

Interventionscore on a scale (Mean)
4-aminopyridine19.8
Placebo22.8

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Walk

Timed 25 Foot Walk Test (T25-FW). The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. TIME LIMIT PER TRIAL (2) 3 minutes (180 seconds) per trial. (NCT02280096)
Timeframe: 5-10 minutes

Interventionseconds (Mean)
4-aminopyridine15.2
Placebo10.4

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Rey-Osterrieth Complex Figure Test (ROCF)

The purpose of this test is to assess visual-spatial constructional ability and visual memory. The time required to copy the drawing is recorded. Less time indicates a better performance and more time indicates a worse outcome (min score 60 and max score 300 seconds). (NCT02280096)
Timeframe: 10-15 minutes

Interventionunits on a scale (seconds) (Mean)
4-aminopyridine208.6
Placebo231.2

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Integrated Program of Neuropsychological Exploration Test Barcelona

Integrated Program of Neuropsychological Exploration Test Barcelona: Digit Span Forward (DSF), (attention spam and improved scoring metrics significantly enhance the precision of DSF assessments of short-term verbal memory). Digit sequences are presented beginning with a length of two digits and two trials are presented at each increasing list length. Max score 8 and min score 0 digits. Higher scores indicate a better cognitive performance. (NCT02280096)
Timeframe: 7-10 min

Interventioncorrect numbers recalled (Mean)
4-aminopyridine6.1
Placebo5

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Five Digit Test (FDT). Processing Speed

Processing speed information (which includes reading, count, and alternation speed). Cards with a different number of stimuli are shown to the patient, who has to read, count, and respond to a change of instructions (alternation). Reading speed (min 12, max 31+ seconds), counting speed (min 14, max 28+ seconds), and alternation speed (min 26, max 56+ seconds) are recorded. Less speed corresponds to a better outcome. (NCT02280096)
Timeframe: 8-10 min

,
Interventionseconds (Mean)
Reading speedCount speedAlternation speed
4-aminopirydine2830.560.3
Placebo29.634.258.8

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Fatigue

The Fatigue Severity Scale (FSS) is one of the most frequently used inventories for measuring fatigue in people with chronic illnesses. The FSS questionnaire is comprised of nine statements inquiring about the examinee's sleep habits over the preceding week. Ratings are on a 7-point Likert scale, where higher scores indicate how strongly the patient agrees with the nine statements.Scale. Scoring using a bimodal response system or a Likert score with weights assigned to each response choice. Likert or bimodal rating scales with 4 response options. For the Likert Scale: better than usual= 0, no more than usual= 1, worse than usual= 2, much worse than usual= 3. For the bimodal scale: better than usual= 0, no more than usual= 0, worse than usual= 1, much worse than usual= 1. Sum all items for a total score. Score range. Range is 0 -11 for bimodal response format. Interpretation of scores. Higher score indicates more fatigue. Self report scale (NCT02280096)
Timeframe: 10 minutes

Interventionscore on a scale (Mean)
4-aminopirydine4.3
Placebo3.3

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Color Trails Test (CTT)

Measure sustained attention. The CTT uses numbered coloured circles and universal sign language symbols. The circles are printed with vivid pink or yellow backgrounds that are perceptible to colourblind individuals. For the Colour Trails 1 trial, the respondent uses a pencil to rapidly connect circles numbered 1 through 25 in sequence. Less time indicates better performance (min=10, max= 240). (NCT02280096)
Timeframe: 5-8 minutes

Interventionunits on a scale (seconds) (Mean)
4-aminopyridine68.91
Placebo67.3

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The Brief Repeatable Battery of Rao

Neuropsychological tests to assess: verbal fluency. Participants have to say as many words as possible from a category in a given time 60 Sec (F, A, S) Max score 72 and min score 19 words. Higher scores indicate a better cognitive performance. (NCT02280096)
Timeframe: 10-15 minutes

InterventionCorrect words (Mean)
4-aminopyridine42.09
Placebo35.5

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Pulse Size Ratio (PSR): Abducting/Adducting Eye Ratio for Saccadic Peak Velocity.

For each saccade made by the subject, the ratio of the maximum velocity (deg/sec) of the eye moving away from the nose and of the eye moving towards the nose was calculated. Subjects' horizontal saccades were recorded for 10 minutes, and an average of PSR for all saccades recorded was taken. (NCT02391961)
Timeframe: Average PSR values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

,
Interventionratio (Mean)
average pulse size ratio baselineaverage pulse size ratio after 3 hours
Dalfampridine1.9141.805
Placebo1.9371.898

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National Eye Institute (NEI) Visual Function Questionnaire 25 (VFQ-25)

We used a validated questionnaire to assess visual disability, the National Eye Institute (NEI) Visual Function Questionnaire 25. Min value 0; Max value 100; Higher scores mean a better outcome. (NCT02391961)
Timeframe: VFQ25 was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

Interventionscore on a scale (Mean)
Dalfampridine73.48
Placebo71.62

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Reading Acuity (RA)

MNREAD acuity charts for reading acuity (RA) (NCT02391961)
Timeframe: Average RA values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

,
InterventionlogMAR for RA (Mean)
RA at baselineRA after 3 hours
Dalfampridine0.1110.088
Placebo0.1080.086

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10-Item Neuro-Ophthalmic Supplement (NOS)

We used a validated questionnaire to assess visual disability, the 10-Item Neuro-Ophthalmic Supplement. Min value 0; Max value 100; Higher scores mean a better outcome. (NCT02391961)
Timeframe: 10-Item NOS was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

Interventionscore on a scale (Mean)
Dalfampridine64.9
Placebo64.3

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Gait Assessment

25-foot Walk Test (FWT) (NCT02391961)
Timeframe: Measures were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

,
Interventionseconds (Mean)
25 FWT baseline25 FWT after 3 hours
Dalfampridine8.9868.567
Placebo9.1139.184

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Pulse Time Delay (PTD): Time Difference Between Onset of the Saccade in the Adducting Eye and Onset of the Saccade in the Abducting Eye.

For each saccade made by the subject, we calculated the difference (in sec) between the onset (based on a velocity threshold) of the movement in the adducting eye (the eye moving towards the nose) and the onset of the movement in the abducting eye (the eye moving away from the nose). Subjects' horizontal saccades were recorded for 10 minutes, and an average of PTD for all saccades recorded was taken. (NCT02391961)
Timeframe: Average PTD values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

,
Interventionseconds (Mean)
Average PTD at baselineAverage PTD after 3 hours
Dalfampridine0.0070.008
Placebo0.0070.008

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Maximum Reading Speed (MRS)

MNREAD acuity charts for reading speed (maximum reading speed, MRS) (NCT02391961)
Timeframe: Average MRS values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

,
Interventionwords per minute (Mean)
MRS at baselineMRS after 3 hours
Dalfampridine156158
Placebo151.7158.7

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Change From Baseline on the 10 Meter Walk Test (10MWT)

10 Meter Walk Test (10MWT) and Change from Baseline by Visit (NCT02422940)
Timeframe: Day 1, up to 12 months

,
InterventionMeter /second (Mean)
BaselineVisit 2 (Day 15) Actual ValueVisit 2 (Day 15) Change from BaselineVisit 3 (Month 1) Actual ValueVisit 3 (Month 1) Change from BaselineVisit 4 (Month 2) Actual ValueVisit 4 (Month 2) Change from BaselineVisit 5 (Month 3) Actual ValueVisit 5 (Month 3) Change from BaselineVisit 6 (Month 6) Actual ValueVisit 6 (Month 6) Change from BaselineVisit 7 (Month 9) Actual ValueVisit 7 (Month 9) Change from BaselineVisit 8 (Month 12) Actual ValueVisit 8 (Month 12) Change from BaselineFinal Visit - Actual ValueFinal Visit - Change from Baseline
Dalfampridine-ER 10 mg0.890.940.050.980.060.980.081.000.080.990.071.060.081.080.060.91-0.03
Dalfampridine-ER 7.5 mg0.920.970.050.960.030.990.060.950.051.010.060.990.081.050.071.040.04

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Change From Baseline on the 12-item Health Survey (SF-12)

"The SF-12 v2 (4-week recall) is a general health-related quality-of-life profile measure consisting of 12 items. The SF-12 Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores will be derived and normed to a general United States population for score algorithm. The normalized PCS and MCS scores will be calculated at baseline, Month 12, and subsequent visits.~SF-12 is a Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health." (NCT02422940)
Timeframe: Day 1, up to 12 months

,
Interventionscore on a scale (Mean)
MCS - BaselineMCS - Visit 8 - (Month 12) ActualMCS - Visit 8 - (Month 12) Change from BaselinePCS - BaselinePCS - Visit 8 - (Month 12) ActualPCS - Visit 8 - (Month 12) Change from Baseline
Dalfampridine-ER 10 mg54.454.5-2.437.034.4-2.3
Dalfampridine-ER 7.5 mg54.250.5-4.336.237.32.7

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Change From Baseline on the Stroke Impact Scale (SIS)

The SIS consists of 59 items grouped in 8 domains: strength, hand function, activities of daily living (ADL) / instrumental activities of daily living (IADL), mobility, communication, emotion, memory and thinking, and participation/role function. The subject is asked to rate the level of difficulty in performing each item in the preceding week. Each item is scored on a 5-point scale ranging from 1 (inability to complete the item) to 5 (no difficulty experienced at all). For each domain, the SIS score will be calculated by summing all the items within the domain and transforming into a scale with a range of 0 to 100 as follows: SIS Score = 100 * [(Actual raw score - Lowest possible raw score)/ (Highest possible raw score-Lowest possible raw score)]. (NCT02422940)
Timeframe: Day 1, up to 12 months

,
Interventionscore on a scale (Mean)
SIS ADL/IADL - BaselineSIS ADL/IADL Visit 6 ActualSIS ADL/IADL Visit 6 Change from BaselineSIS ADL/IADL Visit 8 ActualSIS ADL/IADL Visit 8 Change from BaselineSIS Communication - BaselineSIS Communication Visit 6 ActualSIS Communication Visit 6 Change from BaselineSIS Communication Visit 8 ActualSIS Communication Visit 8 Change from BaselineSIS Emotion - BaselineSIS Emotion Visit 6 ActualSIS Emotion Visit 6 Change from BaselineSIS Emotion Visit 8 ActualSIS Emotion Visit 8 Change from BaselineSIS Hand Function - BaselineSIS Hand Function Visit 6 ActualSIS Hand Function Visit 6 Change from BaselineSIS Hand Function Visit 8 ActualSIS Hand Function Visit 8 Change from BaselineSIS Memory & Thinking - BaselineSIS Memory & Thinking Visit 6 ActualSIS Memory & Thinking Visit 6 Change from BaselineSIS Memory & Thinking Visit 8 ActualSIS Memory & Thinking Visit 8 Change from BaselineSIS Mobility - BaselineSIS Mobility Visit 6 ActualSIS Mobility Visit 6 Change from BaselineSIS Mobility Visit 8 ActualSIS Mobility Visit 8 Change from BaselineSIS Participation - BaselineSIS Participation Visit 6 ActualSIS Participation Visit 6 Change from BaselineSIS Participation Visit 8 ActualSIS Participation Visit 8 Change from BaselineSIS Physical Dimension Score (SIS 16) - BaselineSIS Physical Dimension Visit 6 ActualSIS Physical Dim. Visit 6 Change from BaselineSIS Physical Dimension Visit 8 ActualSIS Physical Dim. Visit 8 Change from BaselineSIS Strength - BaselineSIS Strength Visit 6 ActualSIS Strength Visit 6 Change from BaselineSIS Strength Visit 8 ActualSIS Strength Visit 8 Change from BaselineStroke Recovery - BaselineStroke Recovery - Visit 6 ActualStroke Recovery Visit 6 Change from BaselineStroke Recovery Visit 8 ActualStroke Recovery Visit 8 Change from Baseline
Dalfampridine-ER 10 mg75.177.0-0.273.8-0.388.388.60.389.7-2.568.965.7-2.767.03.848.452.31.354.03.382.884.90.987.1-1.072.874.2-0.968.6-2.268.870.71.465.8-3.164.565.1-0.662.8-1.353.352.80.051.8-1.365.066.41.567.41.8
Dalfampridine-ER 7.5 mg71.872.80.472.31.788.688.7-0.183.6-1.267.366.5-1.0164.5-2.645.947.34.646.24.382.884.00.980.70.571.774.51.470.83.564.869.63.465.34.363.665.10.764.01.553.451.5-0.948.5-1.160.364.02.862.40.6

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Subject Global Impression (SGI)

"The Subject Global Impression (SGI) is single item measure of treatment response that asks the subject to rate the effects of the investigational drug on his or her overall walking ability using a 7 point scale ranging from 1 = Terrible to 7 = Delighted." (NCT02422940)
Timeframe: Visit 8 (Month 12)

,
InterventionParticipants (Count of Participants)
7 - Delighted6 - Pleased5 - Somewhat Satisfied4 - Neutral/Mixed3 - Somewhat Dissatisfied2 - Unhappy1 - Terrible
Dalfampridine-ER 10 mg2885001
Dalfampridine-ER 7.5 mg67612110

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Change From Baseline on the Timed up and Go (TUG) Test

The TUG measures mobility and balance and can predict the risk of falls. This test, which was initially called the Get-up and Go test, is considered a measure of dynamic balance. The subject is asked to stand up from a chair, walk 10 feet at a comfortable pace, turn around and be seated. The Timed Up and Go (TUG) is measured in seconds. There will be one practice test and then the timed test. Only the timed test will be analyzed at each visit time point. Reciprocal transformation may be performed if the time values are markedly skewed. (NCT02422940)
Timeframe: Day 1, up to 12 months

,
InterventionSeconds (Mean)
BaselineVisit 2 (Day 15) Actual ValueVisit 2 (Day 15) Change from BaselineVisit 3 (Month 1) Actual ValueVisit 3 (Month 1) Change from BaselineVisit 4 (Month 2) Actual ValueVisit 4 (Month 2) Change from BaselineVisit 5 (Month 3) Actual ValueVisit 5 (Month 3) Change from BaselineVisit 6 (Month 6) Actual ValueVisit 6 (Month 6) Change from BaselineVisit 7 (Month 9) Actual ValueVisit 7 (Month 9) Change from BaselineVisit 8 (Month 12) Actual ValueVisit 8 (Month 12) Change from BaselineFinal Visit - Actual ValueFinal Visit - Change from Baseline
Dalfampridine-ER 10 mg20.1619.82-0.4018.76-0.6118.49-1.3217.39-1.6017.07-1.3615.85-1.0815.17-0.5019.211.25
Dalfampridine-ER 7.5 mg17.9218.590.6717.28-0.5917.57-0.4518.100.0517.750.3322.931.6616.800.3317.381.34

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Change From Baseline on the Two-Minute Walk Test (2MinWT)

2 Minute Walk Test (2MinWT) and Change from Baseline by Visit (NCT02422940)
Timeframe: Day 1, up to 12 months

,
InterventionFeet (Mean)
BaselineVisit 2 (Day 15) Actual ValueVisit 2 (Day 15) Change from BaselineVisit 3 (Month 1) Actual ValueVisit 3 (Month 1) Change from BaselineVisit 4 (Month 2) Actual ValueVisit 4 (Month 2) Change from BaselineVisit 5 (Month 3) Actual ValueVisit 5 (Month 3) Change from BaselineVisit 6 (Month 6) Actual ValueVisit 6 (Month 6) Change from BaselineVisit 7 (Month 9) Actual ValueVisit 7 (Month 9) Change from BaselineVisit 8 (Month 12) Actual ValueVisit 8 (Month 12) Change from BaselineFinal Visit - Actual ValueFinal Visit - Change from Baseline
Dalfampridine-ER 10 mg297.41312.0814.27317.9614.48318.9817.48331.7716.99321.2872342.2419.25360.9019.98318.489.88
Dalfampridine-ER 7.5 mg309.59319.249.72322.9510.81328.0116.67323.2915.44335.2816.38312.9821.88330.0723.65320.3420.23

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Change From Baseline on the Walking Impact Scale (Walk-12)

The Walk-12 is a 12-question questionnaire that asks subjects to rate limitations of their mobility during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). For each visit, the Walk-12 score will be calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. A higher score indicates a greater degree of limitation in walking. A negative change indicates an improvement in walking. 0 = no limitation in mobility to 100 extreme limitation in mobility. Walk-12 Score = 100 * [(Mean of the 12 items) - 1]/(5-1) (NCT02422940)
Timeframe: Day 1, up to 12 months

,
Interventionunits on a scale (Mean)
BaselineVisit 2 (Day 15) Actual ValueVisit 2 (Day 15) Change from BaselineVisit 6 (Month 6) Actual ValueVisit 6 (Month 6) Change from BaselineVisit 8 (Month 12) Actual ValueVisit 8 (Month 12) Change from BaselineFinal Visit - Actual ValueFinal Visit - Change from Baseline
Dalfampridine-ER 10 mg49.7845.95-3.9248.14-2.4049.67-5.7549.00-1.90
Dalfampridine-ER 7.5 mg47.3747.00-0.5742.72-1.9545.47-6.1344.21-9.18

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The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months.

This extension study was designed to evaluate long-term safety, tolerability, and efficacy of dalfampridine-ER (extended release) in adult subjects with chronic post-ischemic stroke walking deficits. Subjects who had completed the placebo-controlled DALF-PS-1016 core study were eligible to enroll regardless of whether they had received active drug or placebo in the core study. (NCT02422940)
Timeframe: up to 12 months

,
InterventionParticipants (Count of Participants)
Subjects with at Least One TEAESubjects with at Least One Serious TEAESubjects by Maximum Severity (Mild)Subjects by Maximum Severity (Moderate)Subjects by Maximum Severity (Severe)Subjects with at least One TEAEA leading to DisconSubjects who Died Due to a TEAE
Dalfampridine-ER 10 mg99845431170
Dalfampridine-ER 7.5 mg10214454314121

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Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)

Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation. (NCT02656160)
Timeframe: 1 night

Intervention%max/cmH2O (Median)
Placebo-0.23
Dalfampridine-0.36

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Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration).

The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns). (NCT02656160)
Timeframe: 1 night

,
Interventionpercentage of wakefulness value (Median)
Tonic genioglossus activity during sleepPhasic genioglossus activity during sleep
Dalfampridine136163
Placebo166245

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Subjective Return of Sensation

"Return of lost sensation after nerve injury attributable to circulating 4-AP. Subjective return of sensation in the injured limb or portion of the limb.~Patients for this trial are not able to sense in portions of their limbs. The measure will be sensation, measured on the binary scale of yes or no (able to feel the extremity versus unable to feel) This is assessed through clinical examination of the injured limb." (NCT04026568)
Timeframe: During dosing of drug intervention (5 hours) and 2, 6, 9, 12, 15, 20 weeks post injury

Interventionparticipants (Number)
Return of sensation prior to administration of study drug-baselineReturn of sensation 1 hour post study drug administrationReturn of sensation 2 hours post study drug administrationReturn of sensation 3 hours post study drug administrationReturn of sensation 4 hours post study drug administrationReturn of sensation 5 hours post study drug administrationReturn of sensation 2 weeks post injuryReturn of sensation 6 weeks post injuryReturn of sensation 9 weeks post injuryReturn of sensation 12 weeks post injuryReturn of sensation 15 weeks post injuryReturn of sensation 18 weeks post injuryReturn of sensation 20 weeks post injury
Placebo000000000NANANANA

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