A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)

NCT04659161 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: KAR-007
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 22

Brief Summary

This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in adult subjects who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily \[BID\]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in disease severity and symptoms, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia.

Conditions

Schizophrenia; Schizophrenia; Psychosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5

  The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

  Baseline and Week 5

Secondary Outcomes (5)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5

  Baseline and Week 5

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5

  Baseline and Week 5

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score

  Baseline and Week 5

• Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5

  Baseline and Week 5

• Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5

  Baseline and Week 5

Study Arms (2)

KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

Oral xanomeline 50 mg/trospium chloride 20 mg BID (twice a day) for the first 2 days (Days 1 and 2) followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the subject was continuing to experience adverse events (AEs) from the previous dose of KarXT 100/20 BID. All subjects who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.

Also known as: KarXT

KarXT

Placebo DRUG

Placebo Capsules twice a day (BID)

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is aged 18 to 65 years, inclusive, at screening.
• Subject is capable of providing informed consent.
• A signed informed consent form must be provided before any study assessments are performed.
• Subject must be fluent (oral and written) in English to consent
• Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
• Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.
• The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.
• If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.
• Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:
• Item 1 (P1; delusions)
• Item 2 (P2; conceptual disorganization)
• Item 3 (P3; hallucinatory behavior)
• Item 6 (P6; suspiciousness/persecution)
• Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%.
• Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.

You may not qualify if:

• Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before they can be allowed into the study.
• Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
• Subjects with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
• Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
• Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening.
• Subjects cannot currently (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) be receiving oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (eg, lamotrigine, Depakote); tricyclic antidepressants (eg, imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate).
• Pregnant, lactating, or less than 3 months postpartum.
• If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.
• Positive test for coronavirus (COVID-19) within 2 weeks before screening and at screening.
• Subjects with extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.
• Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.
• Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) or required clozapine within the last 12 months.

Sponsors & Collaborators

• Karuna Therapeutics: lead

Study Sites (22)

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

CITrials

Bellflower, California, 90706, United States

Location

ProScience Research Institute

Culver City, California, 90230, United States

Location

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

CNS Network

Long Beach, California, 90806, United States

Location

Catalina Research Institute, LLC

Montclair, California, 91763, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

California Neuropsychopharmacology Clinical Research Institute

Pico Rivera, California, 90660, United States

Location

California Neuropsychopharmacology Clinical Research Institute

San Diego, California, 92101, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Innovative Clinical Research, Inc.

Miami Lakes, Florida, 33016, United States

Location

Research Centers of America

Oakland Park, Florida, 33334, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Pillar Clinical Research

Lincolnwood, Illinois, 60712, United States

Location

Arch Clinical Trials

St Louis, Missouri, 63118, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

Neuro-Behavioral Clinical Research

North Canton, Ohio, 44720, United States

Location

Community Clinical Research

Austin, Texas, 78754, United States

Location

Pillar Clinical Research

Richardson, Texas, 75080, United States

Location

Related Publications (4)

• Yeung PP, Breier A, Zhu H, Kaul I, Marcus RN. Xanomeline and Trospium Chloride for the Treatment of Agitation Associated With Schizophrenia: PANSS-Excited Component Results From 3 Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Mar 24;86(2):24m15668. doi: 10.4088/JCP.24m15668.

  PMID: 40215379 DERIVED

• Citrome L, Neugebauer NM, Meli AA, Kando J. Xanomeline and Trospium Chloride Versus Placebo for the Treatment of Schizophrenia: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. Neuropsychiatr Dis Treat. 2025 Apr 5;21:761-773. doi: 10.2147/NDT.S503494. eCollection 2025.

  PMID: 40212458 DERIVED

• Kaul I, Claxton A, Sawchak S, Sauder C, Brannan SK, Raj E, Ruan S, Konis G, Brown D, Cutler AJ, Marcus R. Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Feb 26;86(1):24m15497. doi: 10.4088/JCP.24m15497.

  PMID: 40047530 DERIVED

• Kaul I, Sawchak S, Correll CU, Kakar R, Breier A, Zhu H, Miller AC, Paul SM, Brannan SK. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet. 2024 Jan 13;403(10422):160-170. doi: 10.1016/S0140-6736(23)02190-6. Epub 2023 Dec 14.

  PMID: 38104575 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Inder Kaul, VP Clinical Development
• Organization: Karuna Therapeutics, Inc.

medinfo@karunatx.com

1-888-783-0380

Study Officials

• Inder Kaul, MD

  Karuna Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 9, 2020
• Study Start: December 16, 2020
• Primary Completion: May 24, 2022
• Study Completion: May 24, 2022
• Last Updated: December 12, 2023
• Results First Posted: December 12, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)