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Completed

NCT Number: NCT05919823

A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia

A Phase 3, Multicenter, Two-part Study with a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects with DSM-5 Schizophrenia

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Anhui Mental Health Center, Hefei, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject is Chinese national, aged 18 to 65 years, inclusive, at screening.
  • Subject is capable of providing written informed consent.
  • Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 and MINI.
  • 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 at screen.
  • If already an inpatient at screening, hospitalization has to be ≤2 weeks for the current exacerbation at the time of screening.
  • PANSS total score between 80 and 120,inclusive, with a scores 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 able to be confined to an inpatient setting for the duration of the 5-week double-blind part of the study, follow instructions, and comply with the protocol requirements.
  • Body mass index of 18 to 40 kg/m2, inclusive.
  • 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. An informant is needed at the screening and baseline visits as well as at the end of the study for relevant assessments (site staff may act as informant while the subject is an inpatient). An informant may not be necessary if the subject has been a patient of the investigator for ≥1 year.
  • Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP must be willing and able to adhere to the contraception guidelines.

Exclusion criteria

  • Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
  • 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 human immunodeficiency virus (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 C-SSRS.
  • Clinically significant abnormal findings on the physical examination, medical history, electrocardiogram, or clinical laboratory results at screening that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
  • Subjects are receiving or have recently received (within 5 half-lives or 1 week, whichever is longer, before baseline [Day -1]) oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (e.g., lamotrigine, valproate); tricyclic antidepressants (e.g., imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate).
  • Subjects are receiving or have recently received (within 1 week before baseline [Day -1]) metformin.
  • Pregnant, lactating, or less than 3 months postpartum.
  • 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.
  • 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 has required clozapine within the last 12 months.
  • Subjects with prior exposure to KarXT.
  • Subjects who experienced any significant adverse effects due to trospium chloride.
  • Participation in another clinical study within 3 months before screening in which the subject received an experimental or investigational drug agent.
  • Significant risk of violent or destructive behavior.

Treatment and study plan

Xanomeline and Trospium Chloride Capsules

Drug

Oral xanomeline 50 mg/trospium 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium 20 mg BID on days 3-7. The dose is increased to xanomeline 125 mg/trospium 30 mg BID on days 8-35 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium 30 mg will have the option to return to xanomeline 100 mg/ trospium 20 mg depending on clinical response and tolerability.

Other names: KarXT

Placebo

Drug

Placebo Capsules

Primary outcomes

  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales:

    Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210.

    Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes.

    Baseline is defined as last non-missing assessment prior to the first dose of study drug.

Secondary outcomes

  1. Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes.

    Baseline is defined as last non-missing assessment prior to the first dose of study drug.

  2. Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes.

    Baseline is defined as last non-missing assessment prior to the first dose of study drug.

  3. Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as last non-missing assessment prior to the first dose of study drug.

  4. Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status.

    Baseline is defined as last non-missing assessment prior to the first dose of study drug.

  5. Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period

    Time frame: At Baseline and at Week 5 of the Double-Blind Period

    PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales:

    Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210.

    Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes.

    Baseline is defined as last non-missing assessment prior to the first dose of study drug.

  6. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales:

    Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210.

    Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  7. Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  8. Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  9. Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  10. Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  11. Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period

    Time frame: At Baseline and at Week 12 of the Open-Label Period

    PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales:

    Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210.

    Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes.

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  12. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal

    Time frame: From first dose until study completion (up to approximately 18 weeks)

    Adverse Event (AE):

    An AE is any unfavorable and unintended sign, symptom, or disease that occurs in a participant during a clinical trial, regardless of whether it is related to the study treatment. This includes new conditions or worsening of pre-existing ones.

    Serious Adverse Event (SAE):

    An SAE is an AE that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, causes persistent or significant disability/incapacity, or leads to a congenital anomaly/birth defect. Other events may be considered serious if they require medical intervention to prevent one of these outcomes.

  13. Number of Participants With Orthostatic Vital Sign Events

    Time frame: From first dose until study completion (up to approximately 18 weeks)

    Orthostatic vital signs included blood pressure and heart rate. A participant having sustained orthostatic event is defined as the participant experienced at least one orthostatic event for at least 3 consecutive visits.

  14. Number of Participants With Elevated Liver Function Test Results

    Time frame: At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks)

    ULN = upper limit of normal range.; DB = Double-blind period; OL = Open-label period. Hy's law is defined as an elevated alanine aminotransferase level (>3xULN) or an elevated aspartate aminotransferase (>3xULN) in combination with alkaline phosphatase <2xULN and elevated total bilirubin (>2 x ULN). Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  15. Number of Participants With Elevated Metabolic Syndrome Parameters

    Time frame: At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks)

    ULN = Upper limit of normal; DB = Double-blind period; OL = Open-label period. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  16. Number of Participants With Abnormal Electrocardiogram (ECG) Results

    Time frame: At study baseline and up to study completion (up to approximately 18 weeks)

    Anytime post-baseline includes all assessments from the first dose of study drug until end of study visit in double-blind/open-label part, including unscheduled assessments. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  17. Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater

    Time frame: From first dose to study completion (up to approximately 18 weeks)

    The C-SSRS is a clinician- or self-administered questionnaire assessing suicidal ideation and behavior. It rates ideation severity from 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). It also records the presence or absence of suicidal behaviors, including actual, interrupted, or aborted attempts, and preparatory acts. The highest level of ideation or most severe behavior reported is used to determine suicide risk; higher ideation scores or any suicidal behavior indicate greater risk. Baseline is the last non-missing assessment before first study drug dose.

  18. Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results

    Time frame: At study baseline, open-label baseline, and up to study completion (up to approximately 18 weeks)

    Treatment-emergent parkinsonism is defined as Simpson-Angus Scale total score >3 with a baseline score ≤3. Treatment-emergent akathisia is defined as Barnes Akathisia Rating Scale global clinical assessment score >2 with a baseline score ≤2. Treatment-emergent dyskinesia is defined as any Abnormal Involuntary Movement Scale (AIMS) item 1-7 score ≥3 with a baseline score <3 for the item, or score ≥2 on two or more of AIMS items 1-7 with baseline <2 for the items. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  19. Change From Baseline in Body Weight

    Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks)

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  20. Change From Baseline in Body Mass Index (BMI)

    Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks)

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  21. Change From Baseline in Waist Circumference

    Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 months)

    Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.

  22. Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period

    Time frame: On Day 28 of the Double-Blind Period

    AUC₀-12 (Area Under the Concentration-Time Curve from time zero to 12 hours) is the total amount of drug in the blood measured from the time the drug is given (time zero) up to 12 hours after dosing.

  23. Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period

    Time frame: On Day 28 of the Double-Blind Period

    Cmax is the highest concentration of a drug measured in the blood after it is given.

  24. Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period

    Time frame: On Day 28 of the Double-Blind Period

    Tmax is the amount of time it takes to reach that highest concentration (Cmax) after the drug is given.

Sponsors and collaborators

Lead sponsor

Karuna Therapeutics, Inc., a Bristol Myers Squibb company

Industry

Collaborators

  • Zai Lab (Shanghai) Co., Ltd.

Registry information

Official study title

A Phase 3, Multicenter, Two-part Study With a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) Followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia

Acronym: UNITE-001

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 26, 2023
Registry last updated
Dec 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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