Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)

Rajesh Pahwa, Caroline M. Tanner, Robert A. Hauser, Kapil Dev Sethi, Stuart Isaacson, Daniel Truong, Lynn Struck, April E. Ruby, Natalie L. Mcclure, Gregory T. Went, Mary Jean Stempien

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P=0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P=0.004), 340 mg (P=0.008) and 420 mg (P=0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.

Original languageEnglish (US)
Pages (from-to)788-795
Number of pages8
JournalMovement Disorders
Volume30
Issue number6
DOIs
StatePublished - May 1 2015

Fingerprint

Amantadine
Dyskinesias
Levodopa
Parkinson Disease
Placebos
Hallucinations
Dizziness
Constipation
Capsules
Fatigue
Mouth
Outcome Assessment (Health Care)
Safety

Keywords

  • Amantadine
  • Clinical trial
  • Levodopa-induced dyskinesia
  • Parkinson's disease
  • Randomized controlled trial

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Pahwa, R., Tanner, C. M., Hauser, R. A., Sethi, K. D., Isaacson, S., Truong, D., ... Stempien, M. J. (2015). Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). Movement Disorders, 30(6), 788-795. https://doi.org/10.1002/mds.26159

Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). / Pahwa, Rajesh; Tanner, Caroline M.; Hauser, Robert A.; Sethi, Kapil Dev; Isaacson, Stuart; Truong, Daniel; Struck, Lynn; Ruby, April E.; Mcclure, Natalie L.; Went, Gregory T.; Stempien, Mary Jean.

In: Movement Disorders, Vol. 30, No. 6, 01.05.2015, p. 788-795.

Research output: Contribution to journalArticle

Pahwa, R, Tanner, CM, Hauser, RA, Sethi, KD, Isaacson, S, Truong, D, Struck, L, Ruby, AE, Mcclure, NL, Went, GT & Stempien, MJ 2015, 'Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)', Movement Disorders, vol. 30, no. 6, pp. 788-795. https://doi.org/10.1002/mds.26159
Pahwa R, Tanner CM, Hauser RA, Sethi KD, Isaacson S, Truong D et al. Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). Movement Disorders. 2015 May 1;30(6):788-795. https://doi.org/10.1002/mds.26159
Pahwa, Rajesh ; Tanner, Caroline M. ; Hauser, Robert A. ; Sethi, Kapil Dev ; Isaacson, Stuart ; Truong, Daniel ; Struck, Lynn ; Ruby, April E. ; Mcclure, Natalie L. ; Went, Gregory T. ; Stempien, Mary Jean. / Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). In: Movement Disorders. 2015 ; Vol. 30, No. 6. pp. 788-795.
@article{59196d3bebf2426d81db8b8df82f672e,
title = "Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)",
abstract = "ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27{\%} reduction in UDysRS, P=0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P=0.004), 340 mg (P=0.008) and 420 mg (P=0.018). Adverse events (AEs) were reported for 82{\%}, 80{\%}, 95{\%}, and 90{\%} of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9{\%}, 15{\%}, 14{\%}, and 40{\%} for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.",
keywords = "Amantadine, Clinical trial, Levodopa-induced dyskinesia, Parkinson's disease, Randomized controlled trial",
author = "Rajesh Pahwa and Tanner, {Caroline M.} and Hauser, {Robert A.} and Sethi, {Kapil Dev} and Stuart Isaacson and Daniel Truong and Lynn Struck and Ruby, {April E.} and Mcclure, {Natalie L.} and Went, {Gregory T.} and Stempien, {Mary Jean}",
year = "2015",
month = "5",
day = "1",
doi = "10.1002/mds.26159",
language = "English (US)",
volume = "30",
pages = "788--795",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)

AU - Pahwa, Rajesh

AU - Tanner, Caroline M.

AU - Hauser, Robert A.

AU - Sethi, Kapil Dev

AU - Isaacson, Stuart

AU - Truong, Daniel

AU - Struck, Lynn

AU - Ruby, April E.

AU - Mcclure, Natalie L.

AU - Went, Gregory T.

AU - Stempien, Mary Jean

PY - 2015/5/1

Y1 - 2015/5/1

N2 - ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P=0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P=0.004), 340 mg (P=0.008) and 420 mg (P=0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.

AB - ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P=0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P=0.004), 340 mg (P=0.008) and 420 mg (P=0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.

KW - Amantadine

KW - Clinical trial

KW - Levodopa-induced dyskinesia

KW - Parkinson's disease

KW - Randomized controlled trial

UR - http://www.scopus.com/inward/record.url?scp=84929655995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929655995&partnerID=8YFLogxK

U2 - 10.1002/mds.26159

DO - 10.1002/mds.26159

M3 - Article

C2 - 25650051

AN - SCOPUS:84929655995

VL - 30

SP - 788

EP - 795

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 6

ER -