Trial Outcomes & Findings for A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS (NCT NCT03290131)

Last Updated: 2022-07-15

Results Overview

Total Numeric-Transformed Modified Ashworth Scale (TNmAS) is a 6-point scale to measure abnormality in tone or the resistance to passive movements. Higher score is worse outcome. For each joint, the minimum score is 0; maximum score is 5. The values for each of the 3 main joints are summed for the limb score. The limb with the highest score is the most affected limb (MAL). The highest possible score for a limb is 15. Limb range: 0 to 15. To arrive at total limbs (TL) score the values for all 4 limbs are summed; maximum total limb score is 60. TL range: 0 to 60.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

536 participants

Primary outcome timeframe

84 days

Results posted on

2022-07-15

Participant Flow

Participant milestones

Participant milestones
Measure	AERT 40 mg 40 mg//day Arbaclofen Extended-Release Tablets	AERT 80 mg 80 mg/day Arbaclofen Extended-Release Tablets	Placebo Placebo Tablets
Overall Study STARTED	179	179	178
Overall Study COMPLETED	137	107	159
Overall Study NOT COMPLETED	42	72	19

Reasons for withdrawal

Reasons for withdrawal
Measure	AERT 40 mg 40 mg//day Arbaclofen Extended-Release Tablets	AERT 80 mg 80 mg/day Arbaclofen Extended-Release Tablets	Placebo Placebo Tablets
Overall Study Adverse Event	22	57	11
Overall Study Withdrawal by Subject	18	13	8
Overall Study MS Relapse	2	1	0
Overall Study Unknown reason	0	1	0

Baseline Characteristics

A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AERT 40 mg n=179 Participants 40 mg/day Arbaclofen Extended-Release Tablets	AERT 80 mg n=179 Participants 80 mg/day Arbaclofen Extended-Release Tablets	Placebo n=178 Participants Placebo Tablets	Total n=536 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	179 Participants n=5 Participants	179 Participants n=7 Participants	178 Participants n=5 Participants	536 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	101 Participants n=7 Participants	110 Participants n=5 Participants	319 Participants n=4 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	78 Participants n=7 Participants	68 Participants n=5 Participants	217 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	169 Participants n=5 Participants	172 Participants n=7 Participants	171 Participants n=5 Participants	512 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	171 Participants n=5 Participants	177 Participants n=7 Participants	174 Participants n=5 Participants	522 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Total Numeric-Transformed Modified Ashworth Scale (Most Affected Limb)	7.4 units on a scale STANDARD_DEVIATION 3.24 • n=5 Participants	7.6 units on a scale STANDARD_DEVIATION 3.02 • n=7 Participants	7.6 units on a scale STANDARD_DEVIATION 3.13 • n=5 Participants	7.5 units on a scale STANDARD_DEVIATION 3.1 • n=4 Participants

PRIMARY outcome

Timeframe: 84 days

Outcome measures

Outcome measures
Measure	AERT 40 mg n=179 Participants 40 mg/day Arbaclofen Extended-Release Tablets	AERT 80 mg n=179 Participants 80 mg/day Arbaclofen Extended-Release Tablets	Placebo n=178 Participants Placebo Tablets
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)	-1.7 units on a scale Standard Deviation 1.97	-2.0 units on a scale Standard Deviation 1.78	-1.4 units on a scale Standard Deviation 1.82

PRIMARY outcome

Timeframe: 84 days

The Clinical Global Impression of Change (CGIC) was developed to provide a brief, stand-alone assessment of the clinician's view of the subject's global functioning prior to and after initiating a study medication. The scale ranges from -3 to +3 judging whether the change is significantly worse (-3) to significantly improved (+3). Higher score is better outcome. The CGIC scale will be used to measure the overall change in the subject's condition since starting the study. There is no baseline value because the score is a measure of how the patient changed from baseline (treatment initiation).

Outcome measures

Outcome measures
Measure	AERT 40 mg n=179 Participants 40 mg/day Arbaclofen Extended-Release Tablets	AERT 80 mg n=179 Participants 80 mg/day Arbaclofen Extended-Release Tablets	Placebo n=178 Participants Placebo Tablets
Clinical Global Impression of Change (CGIC)	0.6 units on a scale Standard Deviation 1.0	0.4 units on a scale Standard Deviation 1.23	0.6 units on a scale Standard Deviation 0.94

Adverse Events

AERT 40 mg

Serious events: 7 serious events

Other events: 148 other events

Deaths: 0 deaths

AERT 80 mg

Serious events: 6 serious events

Other events: 154 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 133 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	AERT 40 mg n=179 participants at risk 40 mg/day Arbaclofen Extended-Release Tablets	AERT 80 mg n=179 participants at risk 80 mg/day Arbaclofen Extended-Release Tablets	Placebo n=178 participants at risk Placebo Tablets
Renal and urinary disorders Urinary Tract Disorder	31.3% 56/179 • Number of events 56 • Adverse event data collected over 92 day period.	31.8% 57/179 • Number of events 57 • Adverse event data collected over 92 day period.	37.6% 67/178 • Number of events 67 • Adverse event data collected over 92 day period.
Musculoskeletal and connective tissue disorders Muscular Weakness	24.0% 43/179 • Number of events 43 • Adverse event data collected over 92 day period.	22.3% 40/179 • Number of events 40 • Adverse event data collected over 92 day period.	15.2% 27/178 • Number of events 27 • Adverse event data collected over 92 day period.
General disorders Asthenia	13.4% 24/179 • Number of events 24 • Adverse event data collected over 92 day period.	20.7% 37/179 • Number of events 37 • Adverse event data collected over 92 day period.	15.2% 27/178 • Number of events 27 • Adverse event data collected over 92 day period.
Nervous system disorders Dizziness	15.1% 27/179 • Number of events 27 • Adverse event data collected over 92 day period.	19.6% 35/179 • Number of events 35 • Adverse event data collected over 92 day period.	11.2% 20/178 • Number of events 20 • Adverse event data collected over 92 day period.
Gastrointestinal disorders Nausea	22.3% 40/179 • Number of events 40 • Adverse event data collected over 92 day period.	16.8% 30/179 • Number of events 30 • Adverse event data collected over 92 day period.	15.7% 28/178 • Number of events 28 • Adverse event data collected over 92 day period.
Nervous system disorders Somnolence	11.2% 20/179 • Number of events 20 • Adverse event data collected over 92 day period.	15.1% 27/179 • Number of events 27 • Adverse event data collected over 92 day period.	10.7% 19/178 • Number of events 19 • Adverse event data collected over 92 day period.
Gastrointestinal disorders Vomiting	7.8% 14/179 • Number of events 14 • Adverse event data collected over 92 day period.	10.6% 19/179 • Number of events 19 • Adverse event data collected over 92 day period.	9.0% 16/178 • Number of events 16 • Adverse event data collected over 92 day period.
General disorders Gait Disturbance	1.1% 2/179 • Number of events 2 • Adverse event data collected over 92 day period.	7.8% 14/179 • Number of events 14 • Adverse event data collected over 92 day period.	3.4% 6/178 • Number of events 6 • Adverse event data collected over 92 day period.
Nervous system disorders Headache	2.2% 4/179 • Number of events 4 • Adverse event data collected over 92 day period.	3.4% 6/179 • Number of events 6 • Adverse event data collected over 92 day period.	6.7% 12/178 • Number of events 12 • Adverse event data collected over 92 day period.
General disorders Fatigue	2.2% 4/179 • Number of events 4 • Adverse event data collected over 92 day period.	5.6% 10/179 • Number of events 10 • Adverse event data collected over 92 day period.	3.9% 7/178 • Number of events 7 • Adverse event data collected over 92 day period.
Ear and labyrinth disorders Vertigo	2.8% 5/179 • Number of events 5 • Adverse event data collected over 92 day period.	5.0% 9/179 • Number of events 9 • Adverse event data collected over 92 day period.	2.2% 4/178 • Number of events 4 • Adverse event data collected over 92 day period.

Additional Information

Vice President, Regulatory Affairs and Quality

RVL Pharmaceuticals, Inc.

Phone: 908-809-1300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	AERT 40 mg n=179 participants at risk 40 mg/day Arbaclofen Extended-Release Tablets	AERT 80 mg n=179 participants at risk 80 mg/day Arbaclofen Extended-Release Tablets	Placebo n=178 participants at risk Placebo Tablets
Ear and labyrinth disorders Vertigo	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Gastrointestinal disorders Vomiting	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
General disorders Withdrawal Syndrome	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.
Immune system disorders Urosepsis	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.
Injury, poisoning and procedural complications Contusion	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Injury, poisoning and procedural complications Hip Fracture	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Injury, poisoning and procedural complications Pneumothorax	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.
Nervous system disorders Multiple Sclerosis Relapse	1.1% 2/179 • Number of events 2 • Adverse event data collected over 92 day period.	1.7% 3/179 • Number of events 3 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Nervous system disorders Restless Leg Syndrome	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Nervous system disorders Somnolence	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.
Nervous system disorders Status Epilepticus	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Nervous system disorders Trigeminal Neuralgia	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.
Psychiatric disorders Delirium	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Psychiatric disorders Depression Suicidal	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Psychiatric disorders Somatic Symptom Disorder	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.56% 1/179 • Number of events 1 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/178 • Adverse event data collected over 92 day period.
Skin and subcutaneous tissue disorders Toxic Skin Eruption	0.00% 0/179 • Adverse event data collected over 92 day period.	0.00% 0/179 • Adverse event data collected over 92 day period.	0.56% 1/178 • Number of events 1 • Adverse event data collected over 92 day period.