Clinical trial NCT02274766: Efficacy and Safety Study of ADS-5102 in PD Patients With Levodopa-Induced Dyskinesia
Official title: ADS-5102 (Amantadine HCl) Extended Release Efficacy and Safety Study in Parkinson's Disease Patients With Levodopa-Induced Dyskinesia (EASE LID 3 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyskinesia
Levodopa-Induced Dyskinesia (LID)
Parkinson's Disease (PD)
Keywords: Levodopa-Induced Dyskinesia
LID
Parkinsonism
Parkinson's Disease
Lead sponsor: Adamas Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-24
Enrollment: 77
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 (trained 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 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, in situ cervical cancer, or other definitively treated cancer that is considered cured;
* 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, using one of the following: barrier methods (diaphragm or partner using condoms plus use of spermicidal jelly or foam, preferably double-barrier methods); oral or implanted hormonal contraceptive; intrauterine device (IUD); or vasectomized male partner;
* 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 in the Unified Dyskinesia Rating Scale (UDysRS) Total Score
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in the Standardized PD Home Diary (ON Time Without Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time)
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Fountain Valley
country: United States
state: California
city: Sunnyvale
country: United States
state: California
city: Boca Raton
country: United States
state: Florida
city: Jacksonville
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: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Elkridge
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: West Bloomfield
country: United States
state: Michigan
city: Greensboro
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Tulsa
country: United States
state: Oklahoma
city: Roanoke
country: United States
state: Virginia
city: Kirkland
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Innsbruck
country: Austria
city: Vienna
country: Austria
city: Vienna
country: Austria
city: Bordeaux
country: France
city: Bron
country: France
city: Clermont Ferrand
country: France
city: Lille
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Poitier
country: France
city: Rennes
country: France
city: Rouen
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Beelitz-Heilstätten
country: Germany
state: Brandenburg
city: Göttingen
country: Germany
state: Niedersachsen
city: Leipzig
country: Germany
state: Sachsen
city: Gera
country: Germany
state: Thüringen
city: Stadtroda
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Kassel
country: Germany
city: Marburg
country: Germany
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
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.