Phase 2 Study to Evaluate Safety and Effects of Darifenacin Tablets in Adults with Amyotrophic Lateral Sclerosis

What this Trial Is About

Amyotrophic lateral sclerosis ALS is a progressive neurological disease that causes the death of motor neurons, leading to severe disability and often fatal outcomes. A key early feature of ALS is the loss of connection at neuromuscular junctions NMJs, where specialized glial cells called Perisynaptic Schwann Cells PSCs normally help maintain and repair these connections. Research suggests that reducing activity of muscarinic acetylcholine receptors mAChRs on PSCs may restore their ability to repair NMJs, which could improve function and quality of life for ALS patients. This Phase 2 trial aims to test the safety, tolerability, and effects of the drug Darifenacin, a selective M3 muscarinic receptor antagonist, in adults with ALS. Participants will be randomly assigned to receive either Darifenacin or a placebo in a double-blind manner. The treatment begins with a two-week titration period where patients take 7.5 mg daily, followed by 22 weeks at an increased dose of 15 mg daily two 7.5 mg tablets. Depending on individual response, dose adjustments or temporary stops may occur for safety reasons. The study evaluates how Darifenacin impacts patient safety, muscle strength, neurological function, depression levels, and NMJ innervation. Throughout the 24-week trial, patients will attend regular clinical assessments to monitor their physical and neurological status, muscle strength, and other health measures including depression and respiratory function. Researchers will track outcomes such as safety and tolerability, pharmacokinetics, and functional rating scales specific to ALS. Optional muscle biopsies may be performed with additional safety precautions. The total participation spans approximately six months, with close monitoring to evaluate the drugs impact on ALS progression and patient well-being.

A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS