Xanomeline–trospium beneficial in treatment of schizophrenia

Treatment with the combination of xanomeline plus trospium leads to favourable reduction in positive and negative symptoms in patients with schizophrenia, while being well tolerated, according to data from the phase III EMERGENT-2 trial.

EMERGENT-2 included 252 adult patients with schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. These patients were randomly assigned to receive xanomeline–trospium (n=126) or placebo (n=126) for 5 weeks.

Xanomeline and trospium were given at 50 mg and 20 mg, respectively, twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3–7. From day 8 onwards, xanomeline-trospium dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability.

The primary endpoint of change from baseline to week 5 in PANSS total score was significantly greater with xanomeline–trospium than with placebo (–21.2 vs –11.6 points; least squares mean difference, –9.6, 95 percent confidence interval [CI], –13.9 to –5.2; p<0.0001).

Results for all secondary endpoints also favoured the combination (p<0.05).

In terms of safety, the most common adverse events in the xanomeline–trospium group were constipation (21 percent vs 10 percent), dyspepsia (19 percent vs 8 percent), headache (14 percent vs 12 percent), nausea (19 percent vs 6 percent), vomiting (14 percent vs 1 percent), hypertension (10 percent vs 1 percent), dizziness (9 percent vs 3 percent), gastro-oesophageal reflux disease (6 percent vs 0 percent), and diarrhoea (6 percent vs 3 percent).

There was no significant between-group difference in the frequency of treatment-emergent adverse event rates of extrapyramidal motor symptoms, weight gain, and somnolence, as well as in adverse event-related discontinuation rates.