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SchizophreniaPhase 3NCT04659161

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

A Phase 3 study testing Xanomeline and Trospium Chloride Capsules in people with Schizophrenia and Schizophrenia; Psychosis, run by Karuna Therapeutics, Inc., a Bristol Myers Squibb company at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Schizophrenia, Schizophrenia; Psychosis
What is being tested?
Xanomeline and Trospium Chloride Capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
252 participants
Where
22 sitesUnited States
Study dates
16 Dec 2020to 24 May 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral antipsychotic medications for at least 5 half-lives or 1 week, whichever is longer, before baseline (Day -1).
  • Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA) before baseline visit (Day -1).
  • Subject is willing and able to be confined to an inpatient setting for the study duration, follow instructions, and comply with the protocol requirements.
  • BMI must be ≥18 and ≤40 kg/m2.
  • Subject resides in a stable living situation and is anticipated to return to that same stable living situation after discharge, in the opinion of the investigator.
  • Subject has an identified reliable informant.
  • Women of childbearing potential, or men with sexual partners of childbearing potential, must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of study drug.

Who cannot join

  • 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.
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  • 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.
  • Subjects with prior exposure to KarXT.
  • Subjects who experienced any adverse effects due to xanomeline or trospium.
  • Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before screening.
  • Risk of violent or destructive behavior.
  • Current involuntary hospitalization or incarceration.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • Community Clinical Research

    Austin, Texas, 78754

  • CITrials

    Bellflower, California, 90706

  • Uptown Research Institute

    Chicago, Illinois, 60640

  • ProScience Research Institute

    Culver City, California, 90230

  • iResearch Atlanta, LLC

    Decatur, Georgia, 30030

  • California Clinical Trials Medical Group

    Glendale, California, 91206

  • Altea Research Institute

    Las Vegas, Nevada, 89102

  • Synergy San Diego

    Lemon Grove, California, 91945

  • Pillar Clinical Research

    Lincolnwood, Illinois, 60712

  • Woodland International Research Group, LLC

    Little Rock, Arkansas, 72211

  • CNS Network

    Long Beach, California, 90806

  • Hassman Research Institute

    Marlton, New Jersey, 08053

  • Innovative Clinical Research, Inc.

    Miami Lakes, Florida, 33016

  • Catalina Research Institute, LLC

    Montclair, California, 91763

  • Neuro-Behavioral Clinical Research

    North Canton, Ohio, 44720

  • Research Centers of America

    Oakland Park, Florida, 33334

  • NRC Research Institute

    Orange, California, 92868

  • California Neuropsychopharmacology Clinical Research Institute

    Pico Rivera, California, 90660

  • Pillar Clinical Research

    Richardson, Texas, 75080

  • California Neuropsychopharmacology Clinical Research Institute

    San Diego, California, 92101

  • Schuster Medical Research Institute

    Sherman Oaks, California, 91403

  • Arch Clinical Trials

    St Louis, Missouri, 63118

Other trials in United States

About this study

Official title: A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia

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.

Being tested
Xanomeline and Trospium Chloride Capsules, Placebo
Medical subject headings
Schizophrenia, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Xanomeline and Trospium Chloride CapsulesDrug

    Also called KarXT

    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.

  • PlaceboDrug

    Also called PBO

    Placebo Capsules twice a day (BID)

Study groups in NCT04659161
Study groupRoleWhat they receive
KarXTExperimentalNot described
Receives: Drug: Xanomeline and Trospium Chloride Capsules
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and Week 5

Secondary outcomes (5)

  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive 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. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

    Measured: Baseline and Week 5

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

    The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

    Measured: Baseline and Week 5

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

    The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

    Measured: Baseline and Week 5

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

    The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants.

    Measured: Baseline and Week 5

  5. Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in 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. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.

    Measured: Baseline and Week 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2020
  2. Study start16 Dec 2020
  3. Primary completion24 May 2022
  4. Study completion24 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
252 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04659161
Sponsor's protocol ID
KAR-007
Status last verified
Nov 2023
First submitted
2 Dec 2020
Last updated
12 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40215379

  • 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.

    PubMed 40212458

  • 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.

    PubMed 40047530

  • 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.

    PubMed 38104575

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Xanomeline and Trospium Chloride Capsules in people with Schizophrenia and Schizophrenia; Psychosis, run by Karuna Therapeutics, Inc., a Bristol Myers Squibb company at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5 (time frame: Baseline and Week 5). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04659161, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.

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