Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study) (EASED)

• ClinicalTrials.gov Identifier: NCT01397422
• Recruitment Status: Completed
• First Posted: July 19, 2011
• Results First Posted: November 6, 2017
• Last Update Posted: December 13, 2017
• Sponsor: Adamas Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Adamas Pharmaceuticals, Inc.

Study Description

Brief Summary:

This is a multi-center, randomized, double-blind, placebo-controlled, 4-arm parallel group study to evaluate the tolerability and efficacy of each of three dose levels of ADS-5102 oral capsules, an extended release formulation of amantadine, dosed once daily 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) higher amantadine plasma concentrations during daytime hours when dyskinesia as well as motor and non-motor symptoms of PD are most problematic, ii) low amantadine plasma concentrations overnight, which may reduce the sleep disturbances and vivid dreams occasionally associated with amantadine, and iii) a reduced initial rate of rise in plasma concentration, which is expected to improve overall tolerability of amantadine.

Condition or disease	Intervention/treatment	Phase
Dyskinesia; Levodopa Induced Dyskinesia; Parkinson's Disease	Drug: ADS-5102 (extended release amantadine HCl)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)
• Study Start Date: July 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Treatment A	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
Active Comparator: Treatment B; Low dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
Active Comparator: Treatment C; A mid-dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
Active Comparator: Treatment D; High dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks

Outcome Measures

Primary Outcome Measures :

1. Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score From Baseline to Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ]
   The UDysRS is a dyskinesia rating scale from 0-104, and it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The last observation carried forward (LOCF) method was used for analysis. Participants were summarized according to the actual treatment received.

Secondary Outcome Measures :

1. Change in the Fatigue Severity Score (FSS) From Baseline to Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ]
   The FSS is a 9-item self-reported scale, rating subject experience of fatigue during the previous 7 days. The total score, on a scale from 1-7, is represented by the mean of all answered items. The higher the score, the greater the fatigue severity.
2. Change in Total Objective Score (III, IV) of the UDysRS From Baseline to Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ]
   UDysRS Part III measures objective impairment (dyskinesia severity, anatomic distribution, and type, based on 4 observed activities); and Part IV measures objective disability based on Part III activities. The scores for the 2 Parts combined range from 0-44; a higher score represents more severe dyskinesia.
3. Change in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) From Baseline to Week 8; Based on a Standardized PD Home Diary [ Time Frame: Baseline (Day 1) and Week 8 ]
   A PD home diary was used to score 5 different conditions in 30-minute time intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 8 visit.
4. Change in Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Scores (Parts I, II, III) From Baseline to Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ]
   The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each part had sub scales ranging from normal = 0 to severe = 4.
5. Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms From Baseline to Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ]
   The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement).

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed a current IRB/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 , including any levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation
• Experiencing troublesome dyskinesia following levodopa dosing (peak dose dyskinesia)
• Able to understand and complete a standardized PD home diary, following training

Exclusion Criteria:

• History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation)
• History of seizures or stroke/TIA within 2 years of screening
• History of cancer within 5 years of screening, except adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer
• Estimated GFR < 50 mL/min/1.73m2
• 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, or has a positive pregnancy test result pre-dose
• 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

Contacts and Locations

Locations

United States, Arizona

Sun City, Arizona, United States

United States, California

Fountain Valley, California, United States

Long Beach, California, United States

Los Angeles, California, United States

Oxnard, California, United States

Pasadena, California, United States

Reseda, California, United States

Sunnyvale, California, United States

Ventura, California, United States

United States, Connecticut

Fairfield, Connecticut, United States

United States, Florida

Boca Raton, Florida, United States

Bradenton, Florida, United States

Port Charlotte, Florida, United States

Tampa, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

Augusta, Georgia, United States

United States, Illinois

Chicago, Illinois, United States

Winfield, Illinois, United States

United States, Iowa

Des Moines, Iowa, United States

United States, Kansas

Kansas City, Kansas, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, Michigan

West Bloomfield, Michigan, United States

United States, New Jersey

Toms River, New Jersey, United States

United States, New York

New York, New York, United States

United States, North Carolina

Durham, North Carolina, United States

Raleigh, North Carolina, United States

United States, Ohio

Toledo, Ohio, United States

United States, Oklahoma

Tulsa, Oklahoma, United States

United States, Texas

Houston, Texas, United States

San Antonio, Texas, United States

United States, Virginia

Richmond, Virginia, United States

United States, Washington

Kirkland, Washington, United States

United States, Wisconsin

Milwaukee, Wisconsin, United States

Sponsors and Collaborators

Adamas Pharmaceuticals, Inc.

Investigators

• Study Director: Clinical Trials Director; Adamas Pharmaceuticals, Inc.

More Information

• Responsible Party: Adamas Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01397422
• Other Study ID Numbers: ADS-PAR-AM201
• First Posted: July 19, 2011
• Results First Posted: November 6, 2017
• Last Update Posted: December 13, 2017
• Last Verified: November 2017

Keywords provided by Adamas Pharmaceuticals, Inc.:

Levodopa-induced dyskinesia; Parkinsonism

Additional relevant MeSH terms:

Parkinson Disease; Dyskinesias; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Neurologic Manifestations; Amantadine; Antiparkinson Agents; Anti-Dyskinesia Agents; Antiviral Agents; Anti-Infective Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents