Safety and Efficacy of ADS-5102 in Patients With Multiple Sclerosis and Walking Impairment

Safety and Efficacy of ADS-5102 (Amantadine HCl) Extended Release Capsules in Patients With Multiple Sclerosis and Walking Impairment

This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once daily at bedtime for the treatment of walking impairment in MS. ADS-5102 is designed to be administered once daily at bed time, ADS-5102 achieves higher plasma amantadine concentrations in the early morning, sustained throughout the afternoon, and lower concentrations in the evening when patients are sleeping. ADS-5102 is designed to deliver its primary treatment effect during the day, and potentially reduce the adverse events of immediate-release amantadine when the patient is asleep.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Walking Impairment
• Intervention / Treatment: Drug: ADS-5102; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Florida
    • Sarasota, Florida, United States, 34239
  • Georgia
    • Atlanta, Georgia, United States, 30309
  • Illinois
    • Northbrook, Illinois, United States, 60062
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Patchogue, New York, United States, 11772
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Tennessee
    • Franklin, Tennessee, United States, 37064
  • Texas
    • Dallas, Texas, United States, 75214
  • Washington
    • Kirkland, Washington, United States, 11772

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed a current IRB-approved informed consent form;
• Male or female subjects between 18 and 70 years of age, inclusive;
• Confirmed diagnosis of Multiple Sclerosis according to the 2010 Revised McDonald criteria;
• On a stable regimen of medications taken specifically to treat MS for at least 30 days prior to screening, and willing to continue the same doses and regimens for the duration of study participation;
• Stable physical activity level for at least 30 days prior to screening and willing to continue without change for the duration of study participation;
• Maximum EDSS score during screening of 6.5;
• Sufficient ambulatory ability to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening visit;
• A score on each completed screening T25FW test between 8 and 45 seconds, inclusive;
• 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;
• If taking an antidepressant, must be on a stable dose for at least 60 days prior to screening.

Exclusion Criteria:

• History of seizures within 2 years prior to screening;
• Clinically significant MS relapse with onset less than 30 days prior to screening;
• Presence of vertigo or other vestibular dysfunction that might compromise ability to safely perform the T25FW;
• Received physical therapy within 30 days prior to screening;
• Received systemic steroids within 30 days prior to screening;
• Received dalfampridine, methylphenidate, modafinil, armodafinil, amantadine, and/or any product containing amphetamines, or any treatment specifically for fatigue or to improve walking within 30 days prior to screening;
• Received any botulinum toxin containing product used as antispasmodic agent within 3 months prior to screening;
• History of clinically significant hallucinations due to an MS medication or other/unknown cause, within 2 years prior to screening;
• History of Bipolar Disorder or Psychosis, regardless of treatment;
• Presence of cognitive impairment sufficient, in the opinion of the investigator, to affect the subject's ability to complete study assessments, or which would not be in the subject's best interest to participate in the study;
• History of stroke or TIA within 2 years prior to screening;
• History of cancer within 5 years;
• Presence of untreated angle closure glaucoma;
• 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 a highly effective hormonal method of contraception (an IUD, or vasectomized male partner is also acceptable), in combination with a barrier method, 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;
• Planned elective surgery during study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Oral capsules to be administered once daily at bedtime for 4 weeks
Experimental: ADS-5102 (amantadine HCl extended release)	Drug: ADS-5102; Oral capsules to be administered once daily at bedtime for 4 weeks; Other Names: amantadine HCl extended release

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of ADS-5102 assessed by adverse events, safety-related study drug discontinuations, vital signs, and safety laboratory test	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Timed 25 Foot Walk	Up to 4 weeks
Timed Up and go	Up to 4 weeks
2 Minute Walk Test	Up to 4 weeks
MS Walking Scale-12	Up to 4 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Fatigue Scale for Motor and Cognitive Functions	Up to 4 weeks
Beck's Depression Inventory-2	Up to 4 weeks
Brief International Cognitive Assessment for MS	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Adamas Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 12, 2015
• First Posted (Estimate): June 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 8, 2017
• Last Update Submitted That Met QC Criteria: August 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: ADS-AMT-MS201