Karuna Pharmaceuticals, a company focused on targeting muscarinic receptors for the treatment of central nervous system (CNS) disorders including schizophrenia and Alzheimer’s disease, today announced the dosing of the first subject in a tolerability proof-of-concept study of its proprietary lead product KarXT (xanomeline plus trospium chloride). The study, which will be conducted in up to 70 healthy individuals, aims to evaluate the tolerability of KarXT compared to xanomeline alone.
Exclusively licensed to Karuna, xanomeline is a novel, muscarinic acetylcholine receptor agonist that has demonstrated robust efficacy in treating schizophrenia and psychosis in Alzheimer’s disease; however, it has also been associated with tolerability issues that have hindered its development. In a double-blind, placebo-controlled, monotherapy study in people with schizophrenia, a statistically significant, 24-point reduction over placebo was observed on the Positive and Negative Syndrome Scale (PANSS), a standard tool used to measure symptom severity in people with schizophrenia. By selectively targeting muscarinic receptors in the CNS with the KarXT approach, Karuna aims to reduce the peripheral cholinergic side effects previously seen with xanomeline alone.
“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,” said Andrew Miller, Ph.D., Karuna’s Chief Executive Officer. “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 randomized, double-blind, multiple-dose study will dose up to 70 healthy volunteers aged 18 to 60 for in-clinic treatment over the course of nine days. Following a two-day run-in period with trospium alone, subjects will receive xanomeline with either trospium chloride or placebo. Top-line results are expected by the end of 2016.