US-based clinical-stage drug development company Karuna Pharmaceuticals has begun its proof-of-concept study of KarXT for Alzheimer’s disease by dosing its first patient.
KarXT features a combination of xanomeline, which acts as a muscarinic acetylcholine receptor agonist, and trospium chloride, a muscarinic receptor antagonist that has been shown not to enter the central nervous system (CNS).
The muscarinic receptors in the nervous system fuse with the acetylcholine (a neurotransmitter) and an activation of muscarinic receptors outside of the brain leads to side effects such as GI adverse events.
The randomised, double-blind, multiple-dose trial will study the tolerability of KarXT compared to xanomeline alone in 70 healthy individuals.
The volunteers will undergo an in-clinic treatment for nine days. After a two-day run-in period with trospium alone, the volunteers will be administered with xanomeline and either trospium chloride or placebo.
Karuna CEO Andrew Miller said: “In clinical studies, xanomeline has shown robust efficacy in people with schizophrenia and in people with Alzheimer’s disease, demonstrating the immense potential of targeting the M1/M4 muscarinic acetylcholine receptors; however, the muscarinic field has been stymied by tolerability concerns caused by activation of muscarinic receptors in peripheral tissues.
“By combining xanomeline with trospium chloride, we aim to unlock the therapeutic potential of M1/M4 agonists and address the significant unmet need in treating these disorders.”
The company is expecting to report the top-line results of the proof-of-concept study by the end of this year.