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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03436199
• Other study ID #: ADS-AMT-MS301
• Status: Completed
• Phase: Phase 3
• Start date: March 29, 2018
• Est. completion date: December 10, 2019

Study information

• Verified date: December 2021
• Source: Adamas Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 558
• Est. completion date: December 10, 2019
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis
• Walking Impairment

Intervention

Drug:
• ADS-5102, 137 mg
Oral capsules
• ADS-5102, 274 mg
Oral capsules

Other:
• Placebo
Oral capsules

Locations

Country	Name	City	State
Canada	Adamas Clinical Site	Burnaby	British Columbia
Canada	Adamas Clinical Site	Edmonton	Alberta
Canada	Adamas Clinical Site	Greenfield Park	Quebec
Canada	Adamas Clinical Site	Lethbridge	Alberta
Canada	Adamas Clinical Site	Montréal	Quebec
Canada	Adamas Clinical Site	Quebec City	Quebec
United States	Adamas Clinical Site	Albuquerque	New Mexico
United States	Adamas Clinical Site	Amherst	New York
United States	Adamas Clinical Site	Atlanta	Georgia
United States	Adamas Clinical Site	Aurora	Colorado
United States	Adamas Clinical Site	Carlsbad	California
United States	Adamas Clinical Site	Centerville	Ohio
United States	Adamas Clinical Site	Charleston	South Carolina
United States	Adamas Clinical Site	Charlotte	North Carolina
United States	Adamas Clinical Site	Cleveland	Ohio
United States	Adamas Clinical Site	Colorado Springs	Colorado
United States	Adamas Clinical Site	Columbus	Ohio
United States	Adamas Clinical Site	Cordova	Tennessee
United States	Adamas Clinical Site	Cullman	Alabama
United States	Adamas Clinical Site	Denver	Colorado
United States	Admas Clinical Site	Detroit	Michigan
United States	Adamas Clinical Site	Fairfield	Connecticut
United States	Adamas Clinical Site	Farmington Hills	Michigan
United States	Adamas Clinical Site	Fort Collins	Colorado
United States	Adamas Clinical Site	Foxboro	Massachusetts
United States	Adamas Clinical Site	Franklin	Tennessee
United States	Adamas Clinical Site	Fresno	California
United States	Adamas Clinical Site	Fullerton	California
United States	Adamas Clinical Site	Golden Valley	Minnesota
United States	Adamas Clinical Site	Great Falls	Montana
United States	Adamas Clinical Site	Greer	South Carolina
United States	Adamas Clinical Site	Houston	Texas
United States	Adamas Clinical Site	Houston	Texas
United States	Adamas Clinical Site	Indian Land	South Carolina
United States	Adamas Clinical Site	Indianapolis	Indiana
United States	Adamas Clinical Site	Johnson City	Tennessee
United States	Adamas Clinical Site	Kansas City	Kansas
United States	Adamas Clinical Site	Kansas City	Missouri
United States	Adamas Clinical Site	Kirkland	Washington
United States	Adamas Clinical Site	Lake Success	New York
United States	Adamas Clinical Site	Las Vegas	Nevada
United States	Adamas Clinical Site	Lenexa	Kansas
United States	Adamas Clinical Site	Lexington	Massachusetts
United States	Adamas Clinical Site	Lincoln	Nebraska
United States	Adamas Clinical Site	Long Beach	California
United States	Adamas Clinical Site	Maitland	Florida
United States	Adamas Clinical Site	Miami	Florida
United States	Adamas Clinical Site	Milwaukee	Wisconsin
United States	Adamas Clinical Site	Naples	Florida
United States	Adamas Clinical Site	New London	Connecticut
United States	Adamas Clinical Site	New York	New York
United States	Adamas Clinical Site	Newport Beach	California
United States	Adamas Clinical Site	Newport News	Virginia
United States	Adamas Clinical Site	Norfolk	Virginia
United States	Adamas Clinical Site	Northbrook	Illinois
United States	Adamas Clinical Site	Oklahoma City	Oklahoma
United States	Adamas Clinical Site	Omaha	Nebraska
United States	Adamas Clinical Site	Orlando	Florida
United States	Adamas Clinical Site	Ormond Beach	Florida
United States	Adamas Clinical Site	Overland Park	Kansas
United States	Adamas Clinical Site	Palm Coast	Florida
United States	Adamas Clinical Site	Patchogue	New York
United States	Adamas Clinical Site	Philadelphia	Pennsylvania
United States	Adamas Clinical Site	Phoenix	Arizona
United States	Adamas Clinical Site	Plainview	New York
United States	Adamas Clinical Site	Port Charlotte	Florida
United States	Adamas Clinical Site	Portland	Oregon
United States	Adamas Clinical Site	Raleigh	North Carolina
United States	Adamas Clinical Site	Rochester	New York
United States	Adamas Clinical Site	Round Rock	Texas
United States	Adamas Clinical Site	Sacramento	California
United States	Adamas Clinical Site	Saint Louis	Missouri
United States	Adamas Clinical Site	Salt Lake City	Utah
United States	Adamas Clinical Site	Sarasota	Florida
United States	Adamas Clinical Site	Savannah	Georgia
United States	Adamas Clinical Site	Scottsdale	Arizona
United States	Adamas Clinical Site	Seattle	Washington
United States	Adamas Clinical Site	Seattle	Washington
United States	Adamas Clinical Site	Spartanburg	South Carolina
United States	Adamas Clinical Site	Staten Island	New York
United States	Adamas Clinical Site	Tampa	Florida
United States	Adamas Clinical Site	Tucson	Arizona
United States	Adamas Clinical Site	Vero Beach	Florida
United States	Adamas Clinical Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Adamas Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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