Clinical trial NCT02136914: ADS-5102 for the Treatment of Levodopa Induced Dyskinesia (EASE LID Study)
Official title: Efficacy and Safety of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia in Parkinson's Disease Patients (EASE LID Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyskinesia
Levodopa Induced Dyskinesia (LID)
Parkinson's Disease
Keywords: Levodopa Induced Dyskinesia
LID
Parkinsonism
Lead sponsor: Adamas Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-13
Enrollment: 126
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study to evaluate the efficacy and safety of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) maximal concentrations in the early morning through mid-day, when LID can be troublesome, and ii) lower concentrations in the evening, potentially reducing the negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher doses to be tolerated with a once-nightly ER formulation than can be tolerated with an immediate-release formulation. The once-nightly dosing regimen may also provide enhanced convenience and compliance.

In a previous clinical study, ADS-5102 met its primary endpoint; LID was significantly reduced as measured by the change in UDysRS score over 8 weeks vs. placebo.


Eligibility criteria: Inclusion Criteria:

* Signed a current IRB/REB/IEC-approved informed consent form
* Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
* On a stable regimen of antiparkinson's medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation
* Following diary training, the subject is willing and able to understand and complete the 24-hour PD home diary (caregiver/study partner assistance allowed)
* Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis)

Exclusion Criteria:

* History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation)
* History of seizures within 2 years prior to screening
* History of stroke or transient ischemic attack (TIA) within 2 years prior to screening
* History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer
* Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening
* If female, is pregnant or lactating
* If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment.
* Treatment with an investigational drug or device within 30 days prior to screening
* Treatment with an investigational biologic within 6 months prior to screening
* Current participation in another clinical trial

Primary outcomes:
measure: Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24
timeFrame: Baseline to Week 24
measure: Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time)
timeFrame: Baseline (BL) to Week 12 (W12) and Week 24 (W24)
measure: Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III)
timeFrame: Baseline (BL) to Week 12 (W12) and Week 24 (W24)
measure: Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms
timeFrame: Baseline to Week 12 and Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Sun City
country: United States
state: Arizona
city: Fountain Valley
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Reseda
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Torrance
country: United States
state: California
city: Ventura
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Manchester
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Sunrise
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Weston
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Des Moines
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Bingham Farms
country: United States
state: Michigan
city: West Bloomfield
country: United States
state: Michigan
city: Golden Valley
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Albany
country: United States
state: New York
city: Commack
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Kirkland
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Regina
country: Canada
state: Saskatchewan
Study officials:
affiliation: Adamas Pharmaceuticals, Inc.
name: Clinical Trials Director
role: STUDY_DIRECTOR
References:
citation: Hauser RA, Mehta SH, Kremens D, Chernick D, Formella AE. Effects of Gocovri (Amantadine) Extended-Release Capsules on Motor Aspects of Experiences of Daily Living in People with Parkinson's Disease and Dyskinesia. Neurol Ther. 2021 Dec;10(2):739-751. doi: 10.1007/s40120-021-00256-1. Epub 2021 May 22.
citation: Mehta SH, Pahwa R, Tanner CM, Hauser RA, Johnson R. Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia. Neurol Ther. 2021 Jun;10(1):307-320. doi: 10.1007/s40120-021-00246-3. Epub 2021 Apr 17.
citation: Elmer LW, Juncos JL, Singer C, Truong DD, Criswell SR, Parashos S, Felt L, Johnson R, Patni R. Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease. CNS Drugs. 2018 Apr;32(4):387-398. doi: 10.1007/s40263-018-0498-4.
citation: Pahwa R, Tanner CM, Hauser RA, Isaacson SH, Nausieda PA, Truong DD, Agarwal P, Hull KL, Lyons KE, Johnson R, Stempien MJ. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial. JAMA Neurol. 2017 Aug 1;74(8):941-949. doi: 10.1001/jamaneurol.2017.0943.