Arbaclofen extended-release tablets for spasticity in multiple sclerosis: randomized, controlled clinical trial

Area of Science:

• Neurology
• Pharmacology

Background:

• Baclofen, a GABA-B agonist, treats multiple sclerosis spasticity but has dosing and tolerability issues.
• Arbaclofen, the R-enantiomer of baclofen, is more potent and specific for GABA-B receptors.
• Arbaclofen extended-release offers a 12-hour dosing interval and has shown promise in early trials.

Purpose of the Study:

• To evaluate the efficacy and safety of arbaclofen extended-release tablets in patients with multiple sclerosis-related spasticity.
• To compare arbaclofen extended-release at 40mg/day and 80mg/day against a placebo over 12 weeks.

Main Methods:

• A multicenter, double-blind, placebo-controlled Phase 3 study.
• Adults with multiple sclerosis spasticity were randomized to arbaclofen extended-release (40mg or 80mg daily) or placebo for 12 weeks.
• Co-primary endpoints included changes in the Numeric-transformed Modified Ashworth Scale and Clinical Global Impression of Change.

Main Results:

• Arbaclofen extended-release 40mg/day significantly reduced spasticity compared to placebo (least squares mean difference: -0.39, P < 0.048).
• Both arbaclofen 40mg/day and placebo groups showed improvements in Clinical Global Impression of Change, but the difference was not statistically significant (P = 0.43).
• The 80mg/day dose analysis was considered inferential due to hierarchical testing procedures.

Conclusions:

• Arbaclofen extended-release 40mg/day is effective and safe for treating multiple sclerosis-related spasticity over 12 weeks.
• The 40mg/day dosage demonstrated a significant reduction in spasticity and was well-tolerated.
• Further investigation may be warranted for the 80mg/day dose or longer treatment durations.