Author Of 3 Presentations
P0225 - Phase 3 Study Results Assessing the Efficacy and Safety of ADS-5102 (Amantadine) Extended Release Capsules in MS Patients with Walking Impairment (ID 1919)
Abstract
Background
ADS-5102, FDA-approved as Gocovri, to treat dyskinesia in Parkinson’s disease, has a unique PK profile, such that once daily bedtime dosing provides higher amantadine concentrations from morning throughout the day and lower at night. Based on results from a 60-subject, 4-week, Phase-2 study, INROADS was designed to confirm benefit of ADS-5102 on walking in MS patients.
Objectives
To evaluate the efficacy and safety of ADS-5102 (amantadine) extended release capsules in patients with multiple sclerosis with walking impairment.
Methods
INROADS comprised a 4-week placebo run-in, followed by a 12-week double-blind period. Five hundred ninety-four MS patients with walking impairment from the US or Canada enrolled, and 560 were randomized, 1:1:1, to 274 mg ADS-5102 (n=185), 137 mg ADS-5102 (n=187), or placebo (n=186). The primary endpoint was the proportion of responders (≥20% improvement from baseline measured in ft/sec) in timed 25-foot walk [T25FW] at Week 16, comparing 274 mg ADS-5012 versus placebo. Subjects who did not have a Week 16 assessment were counted as non-responders. Additional outcomes included timed up and go test, 2-minute walk test, and MS walking scale-12. Prespecified subgroups, including prior dalfampridine use, were analyzed.
Results
Baseline characteristics were similar across treatment arms, with mean time since diagnosis 15.9 years, median EDSS 6.0, and mean T25FW 12.4 seconds; 52.5% reported prior dalfampridine use. At Week 16, 274 mg ADS-5102 demonstrated a statistically significantly greater response rate, 21.1% (P=.01) than placebo (11.3%); the response rate for 137 mg ADS-5102 was 17.6% (P=.08). For subjects who completed the study, the response rates were 28.3% (P< .001) for 274 mg, and 19.6% (P=.049) for 137 mg, vs. 11.9% for placebo. Response rates were consistent for subjects with (20.0%, 15.9%, vs. 11.0%) and without (22.5%, 19.2%, vs. 11.6%) prior dalfampridine use. The most commonly reported (>5%) adverse events (AEs) were peripheral edema, dry mouth, fall, constipation, UTI, and insomnia; AEs led to study drug discontinuation for 20.5% (274 mg), 6.4% (137 mg) and 3.8% (placebo) of subjects.
Conclusions
INROADS met its primary objective of showing clinically meaningful benefit in MS walking speed for 274 mg ADS-5102. A dose-response was seen for both efficacy and tolerability. AEs were consistent with the known safety profile of amantadine. Results suggest a role for ADS-5102 to improve walking in patients with MS, particularly those who have tried and discontinued dalfampridine.
P1103 - Moderators of improvements in fatigue impact following a self-management intervention in multiple sclerosis (ID 835)
Abstract
Background
Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). A recent randomized controlled trial (RCT) showed a self-management program for fatigue and a general MS education program that controlled for time and attention had equivalent effects on reducing fatigue impact in adults with MS.
Objectives
Examine moderators of treatment-related improvements in fatigue impact following self-management and education interventions in adults with MS.
Methods
Secondary analysis of a recent RCT (N=218) using multilevel modeling to assess moderators of treatment improvements in fatigue impact through six-month follow-up. Hypothesized moderators included age, gender, cohabitation with or without a spouse/partner, MS subtype (relapsing-remitting MS or progressive MS) as well as baseline depression symptoms, sleep disturbance, and self-efficacy.
Results
Living with or without a spouse/partner moderated intervention effects on fatigue impact through the six-month follow-up (b = -0.23, t(588) = 2.09, p = .04; controlling for MS subtype and income). The findings suggested that, in the fatigue self-management group, participants living with a spouse/partner showed greater improvement in fatigue impact (within group Cohen’s d = 0.55) compared to participants who did not live with a spouse/partner (d = 0.14). However, in the general MS education group, improvements in fatigue impact were similar between participants living with a spouse/partner (d = 0.23) and those who did not live with a spouse/partner (d = 0.50). Age, gender, MS subtype and baseline depression symptoms, sleep disturbance, and self-efficacy did not moderate treatment effects on fatigue impact.
Conclusions
Although the findings are exploratory, this study emphasizes that the presence of a close relationship may facilitate benefit from self-management interventions for MS-related fatigue. Future research should investigate how to promote engaging supportive others in self-management interventions for MS-related fatigue.
P1104 - Pain in ambulatory people with multiple sclerosis and self-reported spasticity (ID 1497)
Abstract
Background
Over 50% of people with multiple sclerosis (PwMS) report chronic pain, primarily in the legs, low back and head. Chronic pain interferes with daily activities, employment, and quality of life. Nonpharmacologic therapies, including exercise, are important for pain management. Spasticity is a known contributor to MS pain, but the effectiveness of stretching for pain, as commonly prescribed for spasticity, has not been investigated.
Objectives
To determine the prevalence and location of self-reported chronic pain in PwMS and spasticity, and whether participation in an education and lower extremity stretching program (STC) is associated with greater pain reduction after six months of exercise than a program focused on range of motion (ROM).
Methods
65 ambulatory PwMS with lower extremity spasticity were randomly assigned to STC or ROM. Both groups had two 2-hour group sessions and were asked to track their exercise for six months. At baseline, chronic pain prevalence and locations were reported. At baseline and 6 months after the sessions, pain severity and interference were measured with the Brief Pain Inventory – Short Form (BPI-SF). Differences between baseline and 6-month scores for all subjects and within each group were compared with paired t-tests.
Results
At baseline, 52% of subjects (34/65, 13 in STC [39.4%], 21 in ROM [65.6%]) reported chronic pain, most frequently in the lower back (73.5%), legs (70.6%), or lower back and legs (88.2%). Twenty of the 34 who reported chronic pain at baseline completed the BPI-SF at 6 months (8 in STC, 12 in ROM). Although pain severity was not significantly decreased in all subjects combined (mean change = -0.59, 95% CI = -1.49 to 0.32, t = -1.36, p=0.19) or separately in STC (mean change = -1.47, 95% CI = -3.28 to 0.34, t = -1.92, p=0.096) or ROM (mean change = 0.00, 95% CI = -1.0 to 1.0, t = 0.00, p=1.0), pain interference was significantly decreased in all subjects combined (mean change = -1.05, 95% CI = -2.03 to -0.07, t = -2.25, p = 0.037). Similar trends were observed in the two groups (STC mean change -1.86, 95% CI = -3.97 to 0.26, t = -2.07, p=0.08. ROM mean change -0.51, 95% CI = -1.55 to 0.53, t = -1.08, p=0.3).
Conclusions
Exercise may help reduce pain interference in PwMS and spasticity. The impact on pain severity, and the relative impact of stretching and ROM exercises is uncertain. A fully-powered study is needed to better understand the impact of different types of exercise on pain severity and interference in MS.