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

A 3-arm, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Assess the Efficacy and Safety of ADS-5102 Amantadine Extended Release Capsules in Multiple Sclerosis Patients With Walking Impairment

This study assessed the efficacy and safety of ADS-5102 (at daily doses of 137 mg or 274 mg) compared with placebo in MS patients with walking impairment.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Walking Impairment
• Intervention / Treatment: Other: Placebo; Drug: ADS-5102, 274 mg; Drug: ADS-5102, 137 mg

Detailed Description

This was a multicenter, 3-arm, randomized, placebo-controlled, double-blind, parallel-group study of ADS-5102 (amantadine) extended release capsules in MS subjects with walking impairment. The study consisted of a screening period (up to 3 weeks), a single-blind placebo run-in period (4 weeks; during which subjects were blinded to treatment), and a double-blind treatment period (12 weeks).

For at least 30 days prior to screening, all subjects were to have received a stable regimen of MS medications, both disease-modifying and symptomatic; these medications were to continue at the same doses and regimens for the duration of the subjects' participation in the study, to the extent compatible with good neurological care. Subjects were not to have used amantadine, dalfampridine, or any 4 aminopyridine or 2,4 diaminopyridine preparation within 30 days prior to screening.

Consented subjects who completed the screening period were to undergo a 4-week single-blind placebo run-in period during which they received placebo as 2 capsules once daily at bedtime.

Subjects who completed the single-blind placebo run-in period and continued to meet study eligibility criteria were randomized with equal probability to 1 of 3 treatment groups: placebo or ADS-5102 at a final dose of 137 mg/day or 274 mg/day. Study drugs were administered as 2 capsules once daily at bedtime.

Subjects were to return to the clinic for safety and efficacy assessments at Week 0 and Week 2 prior to randomization and at Weeks 4 (randomization and baseline visit), 6 (only safety), 8, 12, and 16 after randomization. In addition, telephone visits for safety assessments were conducted at Weeks 5 and 7. Subjects who withdrew from the study before Week 16 were to have an early termination visit that included safety follow-up and efficacy assessments, as appropriate.

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6R 2B7
      • Adamas Clinical Site
    • Lethbridge, Alberta, Canada, T1J 0N9
      • Adamas Clinical Site
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Adamas Clinical Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Adamas Clinical Site
    • Montréal, Quebec, Canada, H3A 2B4
      • Adamas Clinical Site
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Adamas Clinical Site
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • Adamas Clinical Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Adamas Clinical Site
    • Scottsdale, Arizona, United States, 85251
      • Adamas Clinical Site
    • Tucson, Arizona, United States, 85704
      • Adamas Clinical Site
  • California
    • Carlsbad, California, United States, 92011
      • Adamas Clinical Site
    • Fresno, California, United States, 93710
      • Adamas Clinical Site
    • Fullerton, California, United States, 92835
      • Adamas Clinical Site
    • Long Beach, California, United States, 90806
      • Adamas Clinical Site
    • Newport Beach, California, United States, 92663
      • Adamas Clinical Site
    • Sacramento, California, United States, 95817
      • Adamas Clinical Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Adamas Clinical Site
    • Colorado Springs, Colorado, United States, 80907
      • Adamas Clinical Site
    • Denver, Colorado, United States, 80209
      • Adamas Clinical Site
    • Fort Collins, Colorado, United States, 80528
      • Adamas Clinical Site
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Adamas Clinical Site
    • New London, Connecticut, United States, 06320
      • Adamas Clinical Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Adamas Clinical Site
  • Florida
    • Maitland, Florida, United States, 32751
      • Adamas Clinical Site
    • Miami, Florida, United States, 33136
      • Adamas Clinical Site
    • Naples, Florida, United States, 34105
      • Adamas Clinical Site
    • Orlando, Florida, United States, 32806
      • Adamas Clinical Site
    • Ormond Beach, Florida, United States, 32174
      • Adamas Clinical Site
    • Palm Coast, Florida, United States, 32164
      • Adamas Clinical Site
    • Port Charlotte, Florida, United States, 33952
      • Adamas Clinical Site
    • Sarasota, Florida, United States, 34233
      • Adamas Clinical Site
    • Tampa, Florida, United States, 33609
      • Adamas Clinical Site
    • Vero Beach, Florida, United States, 32960
      • Adamas Clinical Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Adamas Clinical Site
    • Savannah, Georgia, United States, 31406
      • Adamas Clinical Site
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Adamas Clinical Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Adamas Clinical Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Adamas Clinical Site
    • Lenexa, Kansas, United States, 66214
      • Adamas Clinical Site
    • Overland Park, Kansas, United States, 66212
      • Adamas Clinical Site
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Adamas Clinical Site
    • Lexington, Massachusetts, United States, 02421
      • Adamas Clinical Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Admas Clinical Site
    • Farmington Hills, Michigan, United States, 48334
      • Adamas Clinical Site
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Adamas Clinical Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Adamas Clinical Site
    • Saint Louis, Missouri, United States, 63110
      • Adamas Clinical Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • Adamas Clinical Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Adamas Clinical Site
    • Omaha, Nebraska, United States, 68198
      • Adamas Clinical Site
  • Nevada
    • Las Vegas, Nevada, United States, 89016
      • Adamas Clinical Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Adamas Clinical Site
  • New York
    • Amherst, New York, United States, 14226
      • Adamas Clinical Site
    • Lake Success, New York, United States, 11042
      • Adamas Clinical Site
    • New York, New York, United States, 10029
      • Adamas Clinical Site
    • Patchogue, New York, United States, 11772
      • Adamas Clinical Site
    • Plainview, New York, United States, 11803
      • Adamas Clinical Site
    • Rochester, New York, United States, 14642
      • Adamas Clinical Site
    • Staten Island, New York, United States, 10306
      • Adamas Clinical Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Adamas Clinical Site
    • Raleigh, North Carolina, United States, 27607
      • Adamas Clinical Site
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Adamas Clinical Site
    • Cleveland, Ohio, United States, 44195
      • Adamas Clinical Site
    • Columbus, Ohio, United States, 43214
      • Adamas Clinical Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Adamas Clinical Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Adamas Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Adamas Clinical Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Adamas Clinical Site
    • Greer, South Carolina, United States, 29650
      • Adamas Clinical Site
    • Indian Land, South Carolina, United States, 29707
      • Adamas Clinical Site
    • Spartanburg, South Carolina, United States, 29307
      • Adamas Clinical Site
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Adamas Clinical Site
    • Franklin, Tennessee, United States, 37064
      • Adamas Clinical Site
    • Johnson City, Tennessee, United States, 37604
      • Adamas Clinical Site
  • Texas
    • Houston, Texas, United States, 77030
      • Adamas Clinical Site
    • Houston, Texas, United States, 77074
      • Adamas Clinical Site
    • Round Rock, Texas, United States, 78681
      • Adamas Clinical Site
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Adamas Clinical Site
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Adamas Clinical Site
    • Norfolk, Virginia, United States, 23502
      • Adamas Clinical Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Adamas Clinical Site
    • Seattle, Washington, United States, 98122
      • Adamas Clinical Site
    • Seattle, Washington, United States, 98101
      • Adamas Clinical Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Adamas Clinical Site

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, at the time of Screening
• Confirmed diagnosis of MS according to the 2017 McDonald criteria
• Current medication regimen must be stable for at least 30 days prior to screening, and subject must be willing to continue the same dosing regimen for the duration of study participation
• Maximum Expanded Disability Status Scale (EDSS) score during screening of 6.5
• Stable physical activity level (inclusive of prescribed physical therapy) for at least 30 days prior to screening and willing to continue without change for the duration of study participation
• A score on each of two completed screening T25FW tests between 8 and 45 seconds, inclusive

Exclusion Criteria:

• Documented inability to tolerate amantadine
• Clinically significant MS relapse with onset less than 30 days prior to screening
• Receipt of dalfampridine (or any 4-aminopyridine or 2,4-diaminopyridine preparation) or amantadine within 30 days prior to screening
• History of seizures within 3 years prior to screening
• History of hallucinations (visual, auditory, or any other type) within 3 years prior to screening
• History of bipolar disorder, schizophrenia, or psychosis, regardless of treatment
• For subjects with a history of major depressive disorder, the presence of active depressive symptoms that, in the opinion of the investigator, would 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
• Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure (at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of the subject standing up, compared to pressures obtained while sitting
• 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. If a sexually active male, does not agree to utilize condoms 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 or 5 half-lives, whichever is longer, prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADS-5102, 137 mg; ADS-5102, administered once daily at bedtime from Week 4 through Week 16	Drug: ADS-5102, 137 mg; Oral capsules; Other Names: amantadine extended release; ADS-5102
Experimental: ADS-5102, 274 mg; ADS-5102, administered once daily at bedtime from Week 4 through Week 16	Drug: ADS-5102, 274 mg; Oral capsules; Other Names: amantadine extended release; ADS-5102
Other: Placebo; placebo, administered once daily at bedtime from Week 4 through Week 16	Other: Placebo; Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed 25 Foot Walk (T25FW, Feet/Second): the Proportion of Subjects With a ≥ 20% Increase in Walking Speed (Measured by T25FW) From Baseline at Week 16 (Responder Analysis)	The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as speed (feet per second). Improvement is indicated by an increase in speed.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed 25 Foot Walk: Change From Baseline at Week 16	The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as or speed (feet per second). Improvement is indicated by an increase in speed.	16 weeks
Timed Up and Go (TUG): Change From Baseline at Week 16	The TUG is a measure of lower extremity strength, balance, and coordination. The subject stands up from a chair, walks 3 meters then turns around and walks back to the chair to sit down. The result is reported in seconds. Improvement is indicated by negative change scores.	16 weeks
2-Minute Walk Test (2MWT): Change From Baseline at Week 16	The 2MWT is a measure of lower extremity function. The subject is instructed to walk as far as possible in 2 minutes, and the distance is measured in meters. Improvement is indicated by positive change scores.	16 weeks

Collaborators and Investigators

• Sponsor: Adamas Pharmaceuticals, Inc.
• Investigators: Study Director: Clinical Trials Director, Adamas Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): December 10, 2019

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 19, 2021
• Last Verified: December 1, 2021

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-MS301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No