Clinical trial NCT03436199: Safety and Efficacy of ADS-5102 in Multiple Sclerosis Patients With Walking Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Walking Impairment
Multiple Sclerosis
Lead sponsor: Adamas Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 558
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 16 weeks
Secondary outcomes:
measure: Timed 25 Foot Walk: Change From Baseline at Week 16
timeFrame: 16 weeks
measure: Timed Up and Go (TUG): Change From Baseline at Week 16
timeFrame: 16 weeks
measure: 2-Minute Walk Test (2MWT): Change From Baseline at Week 16
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Adamas Clinical Site
state: Alabama
city: Phoenix
country: United States
facility: Adamas Clinical Site
state: Arizona
city: Scottsdale
country: United States
facility: Adamas Clinical Site
state: Arizona
city: Tucson
country: United States
facility: Adamas Clinical Site
state: Arizona
city: Carlsbad
country: United States
facility: Adamas Clinical Site
state: California
city: Fresno
country: United States
facility: Adamas Clinical Site
state: California
city: Fullerton
country: United States
facility: Adamas Clinical Site
state: California
city: Long Beach
country: United States
facility: Adamas Clinical Site
state: California
city: Newport Beach
country: United States
facility: Adamas Clinical Site
state: California
city: Sacramento
country: United States
facility: Adamas Clinical Site
state: California
city: Aurora
country: United States
facility: Adamas Clinical Site
state: Colorado
city: Colorado Springs
country: United States
facility: Adamas Clinical Site
state: Colorado
city: Denver
country: United States
facility: Adamas Clinical Site
state: Colorado
city: Fort Collins
country: United States
facility: Adamas Clinical Site
state: Colorado
city: Fairfield
country: United States
facility: Adamas Clinical Site
state: Connecticut
city: New London
country: United States
facility: Adamas Clinical Site
state: Connecticut
city: Washington
country: United States
facility: Adamas Clinical Site
state: District of Columbia
city: Maitland
country: United States
facility: Adamas Clinical Site
state: Florida
city: Miami
country: United States
facility: Adamas Clinical Site
state: Florida
city: Naples
country: United States
facility: Adamas Clinical Site
state: Florida
city: Orlando
country: United States
facility: Adamas Clinical Site
state: Florida
city: Ormond Beach
country: United States
facility: Adamas Clinical Site
state: Florida
city: Palm Coast
country: United States
facility: Adamas Clinical Site
state: Florida
city: Port Charlotte
country: United States
facility: Adamas Clinical Site
state: Florida
city: Sarasota
country: United States
facility: Adamas Clinical Site
state: Florida
city: Tampa
country: United States
facility: Adamas Clinical Site
state: Florida
city: Vero Beach
country: United States
facility: Adamas Clinical Site
state: Florida
city: Atlanta
country: United States
facility: Adamas Clinical Site
state: Georgia
city: Savannah
country: United States
facility: Adamas Clinical Site
state: Georgia
city: Northbrook
country: United States
facility: Adamas Clinical Site
state: Illinois
city: Indianapolis
country: United States
facility: Adamas Clinical Site
state: Indiana
city: Kansas City
country: United States
facility: Adamas Clinical Site
state: Kansas
city: Lenexa
country: United States
facility: Adamas Clinical Site
state: Kansas
city: Overland Park
country: United States
facility: Adamas Clinical Site
state: Kansas
city: Foxboro
country: United States
facility: Adamas Clinical Site
state: Massachusetts
city: Lexington
country: United States
facility: Adamas Clinical Site
state: Massachusetts
city: Detroit
country: United States
facility: Admas Clinical Site
state: Michigan
city: Farmington Hills
country: United States
facility: Adamas Clinical Site
state: Michigan
city: Golden Valley
country: United States
facility: Adamas Clinical Site
state: Minnesota
city: Kansas City
country: United States
facility: Adamas Clinical Site
state: Missouri
city: Saint Louis
country: United States
facility: Adamas Clinical Site
state: Missouri
city: Great Falls
country: United States
facility: Adamas Clinical Site
state: Montana
city: Lincoln
country: United States
facility: Adamas Clinical Site
state: Nebraska
city: Omaha
country: United States
facility: Adamas Clinical Site
state: Nebraska
city: Las Vegas
country: United States
facility: Adamas Clinical Site
state: Nevada
city: Albuquerque
country: United States
facility: Adamas Clinical Site
state: New Mexico
city: Amherst
country: United States
facility: Adamas Clinical Site
state: New York
city: Lake Success
country: United States
facility: Adamas Clinical Site
state: New York
city: New York
country: United States
facility: Adamas Clinical Site
state: New York
city: Patchogue
country: United States
facility: Adamas Clinical Site
state: New York
city: Plainview
country: United States
facility: Adamas Clinical Site
state: New York
city: Rochester
country: United States
facility: Adamas Clinical Site
state: New York
city: Staten Island
country: United States
facility: Adamas Clinical Site
state: New York
city: Charlotte
country: United States
facility: Adamas Clinical Site
state: North Carolina
city: Raleigh
country: United States
facility: Adamas Clinical Site
state: North Carolina
city: Centerville
country: United States
facility: Adamas Clinical Site
state: Ohio
city: Cleveland
country: United States
facility: Adamas Clinical Site
state: Ohio
city: Columbus
country: United States
facility: Adamas Clinical Site
state: Ohio
city: Oklahoma City
country: United States
facility: Adamas Clinical Site
state: Oklahoma
city: Portland
country: United States
facility: Adamas Clinical Site
state: Oregon
city: Philadelphia
country: United States
facility: Adamas Clinical Site
state: Pennsylvania
city: Charleston
country: United States
facility: Adamas Clinical Site
state: South Carolina
city: Greer
country: United States
facility: Adamas Clinical Site
state: South Carolina
city: Indian Land
country: United States
facility: Adamas Clinical Site
state: South Carolina
city: Spartanburg
country: United States
facility: Adamas Clinical Site
state: South Carolina
city: Cordova
country: United States
facility: Adamas Clinical Site
state: Tennessee
city: Franklin
country: United States
facility: Adamas Clinical Site
state: Tennessee
city: Johnson City
country: United States
facility: Adamas Clinical Site
state: Tennessee
city: Houston
country: United States
facility: Adamas Clinical Site
state: Texas
city: Houston
country: United States
facility: Adamas Clinical Site
state: Texas
city: Round Rock
country: United States
facility: Adamas Clinical Site
state: Texas
city: Salt Lake City
country: United States
facility: Adamas Clinical Site
state: Utah
city: Newport News
country: United States
facility: Adamas Clinical Site
state: Virginia
city: Norfolk
country: United States
facility: Adamas Clinical Site
state: Virginia
city: Kirkland
country: United States
facility: Adamas Clinical Site
state: Washington
city: Seattle
country: United States
facility: Adamas Clinical Site
state: Washington
city: Seattle
country: United States
facility: Adamas Clinical Site
state: Washington
city: Milwaukee
country: United States
facility: Adamas Clinical Site
state: Wisconsin
city: Edmonton
country: Canada
facility: Adamas Clinical Site
state: Alberta
city: Lethbridge
country: Canada
facility: Adamas Clinical Site
state: Alberta
city: Burnaby
country: Canada
facility: Adamas Clinical Site
state: British Columbia
city: Greenfield Park
country: Canada
facility: Adamas Clinical Site
state: Quebec
city: Montréal
country: Canada
facility: Adamas Clinical Site
state: Quebec
city: Quebec City
country: Canada
facility: Adamas Clinical Site
state: Quebec
Study officials:
affiliation: Adamas Pharmaceuticals
name: Clinical Trials Director
role: STUDY_DIRECTOR
References: