Table of contents

• Trial overview
• Studies in Alzheimer’s disease
• Studies in schizophrenia
• Studies in bipolar I disorder
• Study designs and endpoints
• Who can participate

Trial overview

The trial data for Trospium Chloride are linked to studies of KarXT, KarX-EC, and NSC001, with Trospium Chloride named directly in the Alzheimer’s disease safety study of NSC001.^[1] Across the dataset, the research focuses on whether these studies are safe, tolerable, and effective in specific patient groups.^[1] Most studies are Phase 3, with one Phase 2 trial in mild to moderate Alzheimer’s disease.^[1]

Studies in Alzheimer’s disease

Several trials study people with Alzheimer’s disease, including mild to moderate Alzheimer’s disease, agitation associated with Alzheimer’s disease, and psychosis associated with Alzheimer’s disease.^[1] One Phase 2 study in mild to moderate Alzheimer’s disease is designed to assess the safety and tolerability of NSC001, with or without trospium, and it measures adverse events, clinical and neurological findings, vital signs, ECG, laboratory tests, and suicidal thoughts or behavior.^[1]

Two Phase 3 studies in mild to moderate Alzheimer’s disease evaluate KarXT + KarX-EC and measure change in ADAS-Cog11 at Week 24 and CIBIC+ at Week 24.^[1] ADAS-Cog11 is a thinking and memory test, while CIBIC+ is a global rating of how the person is doing overall.^[1]

Other Phase 3 studies focus on agitation associated with Alzheimer’s disease and use the CMAI-IPA total score as the main endpoint.^[1] The trial goal is to compare treatment with placebo and see whether symptoms of agitation improve by the end of treatment.^[1]

Two additional Phase 3 studies look at psychosis associated with Alzheimer’s disease and measure change in NPI-C: H+D score from baseline to the end of treatment.^[1] This score focuses on hallucinations and delusions, which are symptoms where a person may see or believe things that are not real.^[1]

Studies in schizophrenia

The schizophrenia trials include adults with inadequately controlled symptoms and one study in adolescents aged 13 to 17 years.^[1] These studies test KarXT against placebo to see whether it can reduce schizophrenia symptoms better than a dummy treatment with no medicine.^[1]

In the completed ARISE study, the main endpoint was change in PANSS total score at Week 6.^[1] PANSS is a scale used to measure the severity of schizophrenia symptoms.^[1]

The adolescent Phase 3 study also uses PANSS total score, but at Week 5, and it is designed for teenagers with schizophrenia aged 13 to 17 years.^[1] A separate one-year schizophrenia study was withdrawn and planned to measure change in the BACS composite cognitive score at Week 24, which is a test of thinking skills.^[1]

Another completed rollover study followed people who finished the KAR-012 trial and focused on long-term safety and tolerability, measuring treatment-emergent adverse events.^[1]

Studies in bipolar I disorder

Several Phase 3 studies examine manic episodes in bipolar I disorder, including mania with mixed features.^[1] Some trials study KarXT alone, while another studies KarXT as add-on treatment with lithium, valproate, or lamotrigine.^[1]

The main endpoint in these studies is change from baseline in YMRS score, measured at Week 3 or Week 5 depending on the trial.^[1] YMRS stands for Young Mania Rating Scale and is used to rate manic symptoms.^[1]

One open-label extension study follows people over the long term to assess safety and tolerability in mania or mania with mixed features in bipolar I disorder.^[1] Its main endpoint is the incidence of treatment-emergent adverse events, meaning new side effects that appear after treatment starts.^[1]

Study designs and endpoints

The studies use several research designs, including interventional, randomized, double blind, placebo-controlled, parallel group, and open-label extension designs.^[1] In an interventional study, participants receive a treatment chosen by the study; in a placebo-controlled study, the treatment is compared with a dummy treatment.^[1]

Common primary endpoints include symptom rating scales, cognitive tests, and safety outcomes.^[1] Safety endpoints include adverse events, serious adverse events, treatment-emergent adverse events, vital signs, ECG, laboratory assessments, and suicidal ideation or behavior in the Phase 2 Alzheimer’s study.^[1]

Effectiveness endpoints include changes in agitation, psychosis, mania, and cognitive impairment.^[1] The trials often compare change from baseline, which means the difference between the first measurement and the later measurement after treatment.^[1]

Who can participate

The studies are built for specific patient groups, not for the general public.^[1] Eligible groups include people with mild to moderate Alzheimer’s disease, agitation associated with Alzheimer’s disease, psychosis associated with Alzheimer’s disease, schizophrenia, adolescent schizophrenia, and bipolar I disorder with mania or mixed features.^[1]

Some bipolar I studies include people already taking lithium, valproate, or lamotrigine, because the trial is testing KarXT as an extra treatment.^[1] The trial records also show that some studies are authorised, some are completed, and one is withdrawn, which gives a picture of where each study stands in the research process.^[1]