scholarly journals Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis

2015 ◽  
Vol 17 (3) ◽  
pp. 138-145 ◽  
Author(s):  
Robert Yapundich ◽  
Angela Applebee ◽  
Francois Bethoux ◽  
Myla D. Goldman ◽  
George J. Hutton ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Extended Release ◽  
Walking Speed ◽  
Walking Distance ◽  
Walk Distance ◽  
Double Blind ◽  
Post Hoc ◽  
6 Minute Walk Test ◽  
Minute Walk Distance ◽  
Minute Walk

Background: Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg. Methods: Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test. Results: At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported. Conclusions: Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed.

scholarly journals Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

2018 ◽  
Vol 25 (4) ◽  
pp. 601-609 ◽  
Author(s):  
Jeffrey A Cohen ◽  
Samuel F Hunter ◽  
Theodore R Brown ◽  
Mark Gudesblatt ◽  
Ben W Thrower ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Extended Release ◽  
The United States ◽  
Timed Up And Go ◽  
Double Blind ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Phase 2 Trial ◽  
Minute Walk

Background: Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS). Objective: Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment. Methods: This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed. Results: A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE—suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed. Conclusion: ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.

scholarly journals 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

2021 ◽  
pp. 135245852110353
Author(s):  
Jeffrey A Cohen ◽  
Michelle H Cameron ◽  
Myla D Goldman ◽  
Andrew D Goodman ◽  
Aaron E Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Extended Release ◽  
Walking Speed ◽  
Testing Procedure ◽  
Double Blind Study ◽  
Phase 3 ◽  
Timed Up And Go ◽  
Double Blind ◽  
Meaningful Improvement

Background: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. Objective: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. Methods: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). Conclusion: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.

scholarly journals A clinical study of pulmonary function tests in patients with COPD exacerbation

2017 ◽  
Vol 4 (6) ◽  
pp. 1645
Author(s):  
Shivaraj A. L. ◽  
Arun B. J. ◽  
George A. D'Souza ◽  
Niranjan Nagaraj
Keyword(s):  
Pulmonary Function Tests ◽  
Walking Distance ◽  
Initial Assessment ◽  
Walk Distance ◽  
College Hospital ◽  
Copd Exacerbations ◽  
Exacerbation Of Copd ◽  
Minute Walk Distance ◽  
Minute Walk

Background: COPD is now recognized as an important cause of morbidity and mortality world over. This study aims to assess the serial change in spirometric values and 6-minute walking distance in COPD patients following exacerbation.Methods: A prospective study of 40 patients who were admitted to St. Johns Medical College Hospital with Acute Exacerbation of COPD. After proper history, initial assessment and evaluation, appropriate treatment started according to standard hospital protocols. Spirometry and 6-minute walk distance (6MWD) was done at discharge and at an interval of two and six months during follow up. All the collected data was tabulated and statistically analysed by using software’s SAS 9.2, SPSS 15.0.Results: Among the 40 patients studied, there was a 9.18% drop in FVC (from 2.83 litres to 2.57 litres), 13.26% change in the FEV1/FVC ratio with a mean drop of 150 ml in FEV1 (1.5 litres to 1.35 litres) and 25 meters decline of 6MWD from 391.45 to 366.63 over 6 months follow up period, although none of them were statistically significant.Conclusions: A drop in FEV1 and (6MWD) minute walk distance was found in our study population over 6 months follow period after COPD exacerbations which is in line with the various study reports available in the literature reinforcing the fact that patients with increased airway inflammation show faster decline in FEV1.

scholarly journals D.08 ACT DMD (Ataluren Confirmatory Trial in Duchenne Muscular Dystrophy): effect of Ataluren on timed function tests (TFT) in nonsense mutation (nm) DMD

2016 ◽  
Vol 43 (S2) ◽  
pp. S15-S15
Author(s):  
N Goemans ◽  
C Campbell ◽  
CM McDonald ◽  
T Voit ◽  
X Luo ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Meta Analysis ◽  
Double Blind Study ◽  
Walk Distance ◽  
Phase 3 ◽  
Double Blind ◽  
Decline Phase ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Confirmatory Trial

Background: Ataluren is the first drug to treat the underlying cause of nmDMD. Methods: ACT DMD is a Phase 3, randomized, double-blind study. Males 7-16 years with nmDMD and a screening six-minute walk distance (6MWD) ≥150 m and <80%-predicted were randomized to ataluren 40 mg/kg/day or placebo for 48 weeks. A pre-specified subgroup included patients with baseline 6MWD 300-400 m. A meta-analysis of the overall ACT DMD population and the ‘ambulatory decline phase’ subgroup of the Phase 2b study (those patients meeting ACT DMD entry criteria) was pre-specified in the statistical plan. Results: In the overall ACT DMD population (N=228), changes in TFTs favored ataluren over placebo: 10-meter walk/run, -1.2s (p=0.117); 4-stair climb, -1.8s (p=0.058); 4-stair descend, -1.8s (p=0.012). In the pre-specified subgroup (n=99), these differences increased to -2.1s, -3.6s, and -4.3s, respectively, and were statistically significant (p<0.01) for 4-stair climb and descend. Results are supported by the meta-analysis (N=291), which demonstrated significant differences (p<0.05) in 10-meter walk/run, 4-stair climb, 4-stair descend. Conclusions: TFT results showed a benefit for ataluren in ACT DMD, and a larger treatment effect in the pre-specified baseline 6MWD 300-400 m subgroup as well as the pre-specified meta-analysis of ACT DMD and the Phase 2b study decline subgroup.Supported By: PTC Therapeutics Inc.

Six-minute walk distance as a measure of functional exercise capacity in multiple sclerosis

2005 ◽  
Vol 27 (22) ◽  
pp. 1365-1371 ◽  
Author(s):  
Sema Savci ◽  
Deniz Inal-Ince ◽  
Hulya Arikan ◽  
Arzu Guclu-Gunduz ◽  
Nilufer Cetisli-Korkmaz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Exercise Capacity ◽  
Walk Distance ◽  
Functional Exercise ◽  
Functional Exercise Capacity ◽  
Minute Walk Distance ◽  
Minute Walk

scholarly journals Extended‐Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 9 (13) ◽  
Author(s):  
Shane Nanayakkara ◽  
Melissa Byrne ◽  
Vivian Mak ◽  
Kaye Carter ◽  
Eliza Dean ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Kansas City ◽  
Extended Release ◽  
Preserved Ejection Fraction ◽  
Walk Distance ◽  
Kansas City Cardiomyopathy Questionnaire ◽  
Minute Walk Distance ◽  
Minute Walk

Background Heart failure with preserved ejection fraction ( HF p EF ) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HF p EF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HF p EF . Methods and Results The Mil HFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double‐blind, placebo‐controlled pilot study in 23 patients with symptomatic HF p EF . Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6‐minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone‐treated patients compared with placebo (+10±13 versus −3±15; P =0.046). Six‐minute walk distance also tended to improve in the treatment group compared with placebo (+22 [−8 to 49] versus −47 [−97 to 12]; P =0.092). Heart rate (−1±5 versus −2±9 bpm; P =0.9) and systolic blood pressure (−3±18 versus +1±12 mm Hg; P =0.57) were unchanged. Early filling velocity/early mitral annular velocity (−0.3±3.0 versus −1.9±4.8; P =0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HF p EF . Further longer‐term studies are warranted to establish the role of this therapeutic approach in  HF p EF . Registration URL : https://www.anzctr.org.au/ ; Unique identifier: ACTRN 12616000619448.

scholarly journals Six Minute Walk Distance and Reference Equations in Normal Healthy Subjects of Nepal

2017 ◽  
Vol 13 (2) ◽  
pp. 97-101
Author(s):  
S.K. Shrestha ◽  
B. Srivastava
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Reference Values ◽  
Walking Distance ◽  
Regression Equations ◽  
Walk Test ◽  
Walk Distance ◽  
Six Minute Walk Test ◽  
Minute Walk Distance ◽  
Minute Walk

Background The self-paced six minute walk test is a simple assessment for sub-maximal functional capacity. It correlates well with sophisticated tests and gives good prediction for morbidity, mortality, quality of life and pulmonary functions.Objective To evaluate six minute walk distance in healthy adults to identify reference values and formulate reference equations.Method We conducted six minute walk test on 250 random volunteers at and above 18 years of age as per standard protocol. Age, gender, height and weight were measured. Pre-test and post-test vital parameters were recorded including pulse oximetry. The six minute walking distance was identified in all subjects. Multiple regression analysis was done to formulate regression equations to predict six minute walking distance. This also correlated age, gender, height, weight, body mass index with six minute walking distance.Result The mean six minute walking distance was 489±86 meters with males walking 509±82 meters and females 445±78 meters. Age, gender, weight and body mass index had significant contribution for prediction of six minute walking distance. Gender was the single most important predictor. Height had the least significance. Depending on coefficients of these variables we formulated three regression equations and tested them for accurate prediction. The two best equations were identified as: Predicted SMWD = 395–1.5xAge+2.47xWT–35.89xGender and Predicted SMWD = 440–1.82xAge–53.07xGender+5.12xBMI.Conclusion Gender, age and height are the most important predictors of six minute walking distance. Reference values and equations for both genders, different age groups with varying weights were derived for local population.

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