Clinical trial NCT02153632: Efficacy and Safety of Amantadine Hydrogen Chloride (HCl) ER Tablets in Parkinson's Disease Subjects With LID
Official title: A Multicenter, Randomized, Placebo-controlled, Double-blind, 26 Week Study to Evaluate the Efficacy and Safety of Amantadine HCl Extended Release Tablets in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesias
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Parkinson's Disease
Levodopa Induced Dyskinesia (LID)
Keywords: Parkinson's Disease
Levodopa Induced Dyskinesia (LID)
LID
Parkinsonism
Dyskinesia
Lead sponsor: Adamas Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-03
Enrollment: 135
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: The purpose of this multi-center, randomized, double-blind, parallel-group, 26 week study is to compare the efficacy and safety of two different dose levels of Amantadine Extended Release Tablets to placebo for the treatment of levodopa induced dyskinesia in patients with Parkinson's disease.

Detailed description: This study was terminated early due to slow enrollment with 135 of 162 planned subjects enrolled. Amantadine HCl ER has been used for many years as a treatment for Parkinson's disease. It has been reported in the literature to effectively treat the motor complications of levodopa, especially dyskinesia, but it must be given 2 to 4 times a day. The purpose of this multi-center, randomized, double-blind, parallel-group, 26 week study is to compare the efficacy and safety of two different dose levels of Amantadine Extended Release Tablets to placebo for the treatment of levodopa induced dyskinesia in patients with Parkinson's disease. The dose will be given once a day in the morning so that amantadine concentrations are maintained throughout the day for treating the levodopa induced dyskinesia, but will be lower during the night, potentially reducing the negative impact of amantadine on sleep.

Eligibility criteria: Inclusion Criteria:

* Signed Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) informed consent form.
* Idiopathic Parkinson's disease per the United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria.
* Male or female 30 to 85 years old.
* Levodopa induced, predictable peak-effect dyskinesia considered problematic and/or disabling.
* Screening serum creatinine level within normal range
* On stable doses of all oral anti-Parkinson's medication, including any levodopa preparation, for 30 days and be willing to remain on the same doses throughout the trial.
* The subject/caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation during the screening period.

Exclusion Criteria:

* Secondary parkinsonian syndrome, such as vascular, postinflammatory,drug-induced, neoplastic and post-traumatic parkinsonism or any atypical parkinsonian syndrome (e.g., Progressive Supranuclear Palsy, Multi-System Atrophy, etc.);
* Use of amantadine within 14 days before study start, or previously had an adverse event to amantadine
* Currently taking neuroleptics and atypical antipsychotic agents, acetylcholinesterase inhibitors, apomorphine, rimantadine, memantine and dextromethorphan and quinidine if used in combination for treating dyskinesia.
* History of neurosurgical intervention for treating Parkinson's s disease (i.e. pallidotomy or implanted with a deep brain stimulator)
* Any medical condition or past medical history that would increase the risk of exposure to Amantadine HCl Extended Release Tablets or interfere with safety and efficacy evaluations.
* History of cancer within 5 years of screening with following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer.
* History or current diagnosis of schizophrenia or bipolar disorder;
* Inadequately treated Major Depressive Disorder. Subjects on stable doses of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) are eligible for the study;
* Is at imminent risk of suicide or had a suicide attempt within 6 months of screening
* History or current diagnosis of Impulse Control Disorder
* Calculated plasma creatinine clearance of \<60 mL/min at screening
* History of or currently has any of the following clinically significant conditions, cardiovascular, respiratory, renal, hepatic, or gastrointestinal disease
* Any clinically significant vital sign, ECG, or laboratory abnormalities;
* A positive test for HIV antibody or history of HIV; hepatitis B surface antigen unless the positive test followed a recent (\<28 days) vaccination for hepatitis B; hepatitis C antibody;
* A positive urine drug test.
* Pregnant or breastfeeding at screening or has a positive pregnancy test
* 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 the screening visit to at least 4 weeks after the completion of study treatment.
* History of alcohol or narcotic substance abuse ≤1 year before screening.
* Has dementia or another psychiatric illness that prevents provision of informed consent.
* Has a known hypersensitivity to the study treatment(s), based on known allergies to drugs of the same class including rimantadine HCl and memantine HCl.
* Has participated in other studies involving investigational drugs or surgeries within the last 30 days or investigational biologics within the last 6 months prior to screening.
* Plans to undergo major elective surgery during the course of the study.
* Received administration of Live Attenuated Influenza Vaccine (LAIV) within 2 weeks.
* Cognitive impairment, as evidenced by a score \<26 on the Montreal Cognitive Assessment (MoCA) at the screening visit.

Primary outcomes:
measure: Unified Dyskinesia Rating Scale
timeFrame: Change from baseline to Day 98
Secondary outcomes:
measure: Mobility State Self-Assessment - Subject Diary Cards
timeFrame: Day 14 and Day 98 of treatment
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Fountain Valley
country: United States
state: California
city: Irvine
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Ventura
country: United States
state: California
city: Boulder
country: United States
state: Colorado
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: North Palm Beach
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Summit
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: Patchogue
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Round Rock
country: United States
state: Texas
city: Orem
country: United States
state: Utah
city: Kirkland
country: United States
state: Washington
city: Ottawa
country: Canada
state: Ontario
city: Rennes
country: France
state: Ille Et Vilaine
city: Amiens
country: France
city: Bron
country: France
city: Clermont-Ferrand
country: France
city: Creteil
country: France
city: Lille
country: France
city: Marseille
country: France
city: Montauban
country: France
city: Nimes
country: France
city: Paris
country: France
city: Poitiers
country: France
city: Toulouse
country: France
city: Haag
country: Germany
state: Bayern
city: Hindenburg
country: Germany
state: Berlin
city: Weissensee
country: Germany
state: Berlin
city: Erbach
country: Germany
state: Hessen
city: Achim
country: Germany
state: Niedersachesen
city: Bochum
country: Germany
state: Nordrhein-Westfalen
city: Berlin
country: Germany
city: Wiesbaden
country: Germany
city: Wurzburg
country: Germany
city: L'Hospitalet De Llobregat
country: Spain
state: Barcelona
city: Manresa
country: Spain
state: Barcelona
city: Sevilla
country: Spain
state: Barcelona
city: Vallés
country: Spain
state: Barcelona
city: Alcorcón
country: Spain
state: Madrid
city: Castellana
country: Spain
state: Madrid
city: Marañón
country: Spain
state: Madrid
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital General de Cataluna
city: Pamplona
country: Spain
Study officials:
affiliation: Osmotica Pharmaceutical US LLC
name: Angela Dentiste, MBA
role: STUDY_CHAIR
References: