Efficacy and Safety of Amantadine Hydrogen Chloride (HCl) ER Tablets in Parkinson's Disease Subjects With LID (ALLAY-LID-II)

• ClinicalTrials.gov Identifier: NCT02153632
• Recruitment Status: Terminated
• First Posted: June 3, 2014
• Results First Posted: April 2, 2019
• Last Update Posted: February 16, 2022
• Sponsor: Adamas Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Adamas Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: May 30, 2014
• First Posted Date: June 3, 2014
• Results First Submitted Date: December 21, 2018
• Results First Posted Date: April 2, 2019
• Last Update Posted Date: February 16, 2022
• Actual Study Start Date: July 30, 2014
• Actual Primary Completion Date: May 20, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2019)

Unified Dyskinesia Rating Scale [ Time Frame: Change from baseline to Day 98 ]

The Unified Dyskinesia Rating Scale is a validated tool for assessment of dyskinesia (involuntary movements) in Parkinson's Disease patients. Rating consists of the change from baseline to Day 98 of the sum of the 26 questions comprising the questionnaire. Each question in the questionnaire is rated on a 5 point scale from 0-4 where 0 is a better outcome. Questions assess: over the past week total hours with dyskinesia and total hours without dyskinesia; problems with speech, chewing and swallowing, eating, dressing, hygiene, handwriting, hobbies, balance, socializing, emotions, spasm or cramps, pain without dystonia and pain from dystonia. The minimum (better) value is 0 and the maximum (worse) value is 130.

Original Primary Outcome Measures (submitted: June 2, 2014)

Unified Dyskinesia Rating Scale [ Time Frame: 14 weeks ]

The change from baseline to Day 98 (Visit 7) of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS)

Current Secondary Outcome Measures (submitted: April 1, 2019)

Mobility State Self-Assessment - Subject Diary Cards [ Time Frame: Day 14 and Day 98 of treatment ]

hange from baseline in the number of awake hours without troublesome dyskinesia (involuntary movements). Every half hour the subject will indicate in the diary if the medication has ("ON") or has not ("OFF") produced benefits in terms of mobility, slowness and rigidity. Valid diaries of the 3 consecutive days prior to each visit will be averaged with respect to the number of awake hours without troublesome dyskinesia. The change from baseline in the number of waking hours that subjects report being "ON" without troublesome dyskinesias will be analyzed at analysis visits Day 14 and Day 98 of treatment. Higher scores mean a better outcome and the maximum value is 24 hours.

Original Secondary Outcome Measures (submitted: June 2, 2014)

• Unified Dyskinesia Rating Scale [ Time Frame: 24 weeks ]
  The change from baseline of treatment in the sum of items comprising the Unified Dyskinesia Rating Scale (UDysRS)
• Mobility State Self Assessment (Subject Diary Cards) [ Time Frame: 24 weeks ]
  The change from baseline in the percent of waking hours that subjects report being "OFF" in the Mobility State Self Assessment (Subject Diary Cards)
• Mobility State Self-Assessment (Subject Diary Cards) [ Time Frame: 24 weeks ]
  The change from baseline in the percent of waking hours that subjects report being "ON" having no dyskinesias, non-troublesome dyskinesias, and troublesome dyskinesias in the Mobility State Self-Assessment (Subject Diary Cards)
• MDS-Unified Parkinson's Disease Rating Scale [ Time Frame: 24 weeks ]
  The change from baseline in the sum of Part II and III of the (MDS-UPDRS)
• Fatigue Severity Scale [ Time Frame: 24 weeks ]
  The change from baseline in the Fatigue Severity Scale (FSS)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Parkinson's Disease
• Levodopa Induced Dyskinesia (LID)

Intervention

• Drug: amantadine HCl ER
  Subjects are given either 240 mg amantadine HCl ER tablet or 320 mg amantadine HCl ER tablet
  Other Name: Osmolex ER Tablet
• Drug: Placebo
  subjects are given an identical placebo tablet
  Other Name: Placebo tablets

Study Arms

• Experimental: 240mg amantadine HCl ER tablets
  amantadine HCl ER, 240 mg tablets, once daily, 22 weeks
  Intervention: Drug: amantadine HCl ER
• Experimental: 320mg amantadine HCl ER tablets
  amantadine HCl ER, 320 mg tablets, once daily, 22 weeks
  Intervention: Drug: amantadine HCl ER
• Placebo Comparator: Placebo Tablets for Amantadine
  Placebo, tablets, once daily, 26 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 15, 2018): 135
• Original Estimated Enrollment (submitted: June 2, 2014): 162
• Actual Study Completion Date: May 20, 2016
• Actual Primary Completion Date: May 20, 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Germany, Spain, United States

Administrative Information

• NCT Number: NCT02153632
• Other Study ID Numbers: OS320-3006
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Adamas Pharmaceuticals, Inc.
• Original Responsible Party: Osmotica Pharmaceutical US LLC
• Current Study Sponsor: Adamas Pharmaceuticals, Inc.
• Original Study Sponsor: Osmotica Pharmaceutical US LLC
• Collaborators: Not Provided

Investigators

• Study Chair: Angela Dentiste, MBA; Osmotica Pharmaceutical US LLC

• PRS Account: Adamas Pharmaceuticals, Inc.
• Verification Date: February 2022