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

A Multicenter, Open-Label Safety and Efficacy Study of ADS-5102 Amantadine Extended Release Capsules in Patients With Multiple Sclerosis and Walking Impairment

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03567057

Enrollment

424

Registered

2018-06-25

Start date

2018-07-18

Completion date

2021-04-18

Last updated

2022-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis, Walking Impairment

Brief summary

This study assessed the long-term safety and tolerability of ADS-5102 in subjects with MS and walking impairment who had completed the double-blind, placebo-controlled study of ADS-5102 in subjects with MS (ADS-AMT-301).

Detailed description

This was a multicenter, open-label study of ADS-5102 (amantadine) extended-release capsules in subjects with MS and walking impairment who completed study drug treatment for 16 weeks and completed a Week 16 visit in Study ADS-AMT-MS301. All enrolled subjects were to receive ADS-5102 at 137 mg for the first week, 205.5 mg for the second week, and 274 mg for the remainder of the 52-week open-label treatment period. Subjects returned to the clinic for safety and efficacy assessments at Weeks 4, 24, and 52. In addition, a telephone visit for safety assessments was conducted at Week 2 and Week 38. Subjects who withdrew from the study prior to completion of the Week 52 visit had an early termination (ET) visit that included safety and efficacy assessments. Subjects who completed 52 weeks of open-label treatment had a final visit for post-treatment safety follow-up and efficacy assessment at Week 54. All study visits and efficacy assessments were to be scheduled to occur at approximately the same time of day for each individual subject. Each subject's efficacy assessment was to be performed by the same clinical rater, if possible.

Interventions

DRUGADS-5102, 274 mg

Oral capsules

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Signed a current IRB-approved informed consent form * Successful completion of a prior double blind study of ADS-5102 in patients with MS walking impairment.

Exclusion criteria

* Based on the judgment of the investigator or Medical Monitor, participation in the study would jeopardize the safety of the subject. * 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 baseline 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. * Anticipated treatment with any amantadine formulation other than ADS-5102 * Planned participation in another interventional clinical trial

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients With Adverse Events	Through study completion, an average of 1 year.	The incidence of treatment-emergent adverse events was used as the measure for long-term safety and tolerability of ADS-5102.

Secondary

Measure	Time frame	Description
Timed 25-Foot Walk (Feet/Second) (Week 24 Value)	24 weeks	The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed.
Timed 25-Foot Walk (Feet/Second) (Week 52 Value)	52 weeks	The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed.
Timed up and go (Baseline Value)	Baseline	The timed up and go 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.
Timed up and go (Week 24 Value)	24 weeks	The timed up and go 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.
Timed 25-Foot Walk (Feet/Second) (Baseline Value)	Baseline	The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed.
2-Minute Walk Test (Baseline Value)	Baseline	The 2-Minute Walk test 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.
2-Minute Walk Test (Week 24 Value)	24 weeks	The 2-Minute Walk test 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.
2-Minute Walk Test (Week 52 Value)	52 weeks	The 2-Minute Walk test 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.
Timed up and go (Week 52 Value)	52 weeks	The timed up and go 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.

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
Placebo/274 mg ADS-5102 Consists of subjects who received placebo in Study ADS-AMT-MS301 and 274 mg ADS-5102 in the current study (ADS-AMT-MS303)	159
137 mg ADS-5102/274 mg ADS-5102 Consists of subjects who received 137 mg ADS-5102 in Study ADS-AMT-MS301 and 274 mg ADS-5102 in the current study (ADS-AMT-MS303)	151
274 mg ADS-5102/274 mg ADS-5102 Consists of subjects who 274 mg ADS-5102 in both Studies ADS-AMT-MS301 and ADS-AMT-MS303	114
Total	424

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	56	53	28
Overall Study	COVID-19 pandemic	4	3	0
Overall Study	Death	1	0	0
Overall Study	Lack of Efficacy	3	0	1
Overall Study	Lost to Follow-up	3	5	2
Overall Study	Medical history event	0	0	1
Overall Study	Non-compliance with study drug	4	2	0
Overall Study	Other	0	0	1
Overall Study	Physician Decision	1	0	0
Overall Study	Unstable medical condition	1	0	0
Overall Study	Withdrawal by Subject	22	24	13

Baseline characteristics

Characteristic	Total	274 mg ADS-5102/274 mg ADS-5102	137 mg ADS-5102/274 mg ADS-5102	Placebo/274 mg ADS-5102
Age, Continuous	54.3 years STANDARD_DEVIATION 9.47	53.0 years STANDARD_DEVIATION 9.4	54.8 years STANDARD_DEVIATION 9.12	54.7 years STANDARD_DEVIATION 9.8
Baseline T25FW <Median of enrolled population (9.4 seconds)	206 Participants	58 Participants	85 Participants	63 Participants
Baseline T25FW >Median of enrolled population (9.4 seconds)	217 Participants	55 Participants	66 Participants	96 Participants
Baseline T25FW Missing	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	52 Participants	12 Participants	20 Participants	20 Participants
Race (NIH/OMB) More than one race	2 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	3 Participants	2 Participants	2 Participants
Race (NIH/OMB) White	360 Participants	99 Participants	128 Participants	133 Participants
Sex: Female, Male Female	284 Participants	76 Participants	100 Participants	108 Participants
Sex: Female, Male Male	140 Participants	38 Participants	51 Participants	51 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	1 / 159	0 / 151	0 / 114
other Total, other adverse events	122 / 159	116 / 151	86 / 114
serious Total, serious adverse events	20 / 159	20 / 151	7 / 114

Outcome results

Primary

Number of Patients With Adverse Events

The incidence of treatment-emergent adverse events was used as the measure for long-term safety and tolerability of ADS-5102.

Time frame: Through study completion, an average of 1 year.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo/274 mg ADS-5102	Number of Patients With Adverse Events	122 Participants
137 mg ADS-5102/274 mg ADS-5102	Number of Patients With Adverse Events	116 Participants
274 mg ADS-5102/274 mg ADS-5102	Number of Patients With Adverse Events	86 Participants

Secondary

2-Minute Walk Test (Baseline Value)

The 2-Minute Walk test 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.

Time frame: Baseline