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AzTrials

SchizophreniaPhase 3NCT04738123

A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-3)

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 32 sites in 2 countries.

Completed

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

Official record
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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
256 participants
Where
32 sitesin 2 countries
Study dates
6 Apr 2021to 7 Dec 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 or local language 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/caregiver.
  • 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

32 sites in 2 countries.

32 sites in 2 countries

United States20 sites

  • Advanced Research Center, Inc.

    Anaheim, California, 92805

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • Community Clinical Research, Inc.

    Austin, Texas, 78754

  • Clinical Innovations, Inc

    Bellflower, California, 90706

  • Pillar Clinical Research

    Bentonville, Arkansas, 72712

  • Hassman Research Institute

    Berlin, New Jersey, 08009

  • AMITA Health Center for Psychiatric Research

    Chicago, Illinois, 60622

  • Uptown Research Institute

    Chicago, Illinois, 60640

  • ProScience Research Group

    Culver City, California, 90230

  • iResearch Atlanta, LLC

    Decatur, Georgia, 30030

  • InSite Clinical Research, LLC

    DeSoto, Texas, 75115

  • Collaborative Neuroscience Research, LLC.

    Garden Grove, California, 92845

  • AMITA Health Center for Psychiatric Research

    Hoffman Estates, Illinois, 60169

  • Behavioral Clinical Research, Inc.

    Hollywood, Florida, 33021

  • Larkin Behavioral Health Services

    Hollywood, Florida, 33021

  • Woodland International Research Group

    Little Rock, Arkansas, 72211

  • CNS Network

    Long Beach, California, 90806

  • Hassman Research Institute

    Marlton, New Jersey, 08053

  • NRC Research Institute

    Orange, California, 92868

  • Artemis Institute for Clinical Research

    San Diego, California, 92103

Other trials in United States

Ukraine12 sites

  • Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov

    Dnipro, 49005

  • Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine

    Kharkiv, 61068

  • Regional Clinical Psychiatric Hospital No. 3, Adult Psychiatric Department No. 3

    Kharkiv, 61068

  • Regional Clinical Psychiatric Hospital No. 3, Psychiatric Department for First Episode Psychosis

    Kharkiv, 61068

  • Kherson Regional Institution of Mental Care

    Kherson, 73488

  • Kyiv City Psychoneurological Hospital #2

    Kyiv, 02192

  • Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic Disorders

    Kyiv, 04080

  • Lviv Regional Clinical Psychiatric Hospital, Department #20

    Lviv, 79021

  • Lviv Regional Clinical Psychiatric Hospital, Department #25

    Lviv, 79021

  • Regional Institution of Mental Psychiatric Care of the Poltava Regional Council

    Poltava, 36013

  • Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council

    Smila, 20708

  • M.I. Pyrogov Vinnytsya National Medical University

    Vinnytsia, 21037

Other trials in Ukraine

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

    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.

  • PlaceboDrug

    Placebo Capsules

Study groups in NCT04738123
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 Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia and is widely used in the study of antipsychotic therapy. 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 positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. 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 the PANSS score at screening.

    Measured: From baseline up to Week 5

Secondary outcomes (33)

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

    PANSS positive score is the sum of all PANSS 7 positive symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility. If a patient has a PANSS assessment recorded and no more than 2 items are missing from the PANSS positive scales, then the PANSS Positive Score will be calculated as the average of the non-missing items multiplied by 7. If 3 or more items are missing (> 30%) at a particular visit, the respective positive score at the visit will not be calculated and will be treated as missing data. Baseline is defined as the PANSS score at screening.

    Measured: From baseline up to Week 5

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

    PANSS negative score is the sum of all PANSS 7 negative symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The negative symptoms in schizophrenia are the diminution or loss of normal functions. If a participant has a PANSS assessment recorded, and no more than 2 items are missing from the PANSS negative scales, then the PANSS Negative Score will be calculated as the average of the non-missing items multiplied by 7. If 3 or more items are missing (> 30%) at a particular visit, the respective negative score at the visit will not be calculated and will be treated as missing data. Baseline is defined as the PANSS score at screening.

    Measured: From baseline up to Week 5

  3. Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score Change From Baseline at Week 5

    PANSS Marder factor score is the sum of 5 negative scales and 2 general scales (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). Participants are rated from 1 to 7 on each symptom scale. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Baseline is defined as the PANSS score at screening.

    Measured: From baseline up to Week 5

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

    Clinical Global Impression-Severity (CGI-S) Score is a measurement to evaluate severity and treatment response in schizophrenia. Completed independently by a clinician, the CGI-S assesses extremely ill patients, by asking 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness. The CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients. This scale reflects the total score. Baseline is defined as CGI-S score at screening. The change from baseline in total score is reported.

    Measured: From baseline up to Week 5

  5. Number of Participants Who Achieve >=30% Reduction in Positive and Negative Symptoms Scale (PANSS) Total Score From Baseline to Week 5

    Positive and Negative Syndrome Scale (PANSS) is a scale used for measuring symptom severity of subjects with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Subjects are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. 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 screening.

    Note: Floor adjusted data were used for this analysis. Floor adjusted total score = total score - 30.

    Measured: From baseline up to Week 5

  6. Number of Participants Experiencing Adverse Events (AEs)

    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

    Measured: From first dose up to Day 42

  7. Number of Participants Experiencing Cholinergic Symptom Adverse Event

    The number of participants experiencing adverse events related to procholinergic symptoms (believed to be associated with xanomeline) and anticholinergic symptoms (believed to be associated with trospium) symptoms. Examples of procholinergic symptoms include vomiting, nausea, diarrhea, sweating and hyper-salivation. Examples of anticholinergic include dizziness, confusion, hallucinations, and somnolence.

    Measured: From first dose up to Day 42

  8. Change From Baseline in Simpson-Angus Scale Total Score (SAS)

    The Simpson-Angus Scale (SAS) is an established instrument to measure drug-related extrapyramidal syndromes. It is a 10-item testing instrument used to assess gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. The range of scores is from 0 to 40 with increased scores indicating increased severity. Baseline is defined as the Simpson-Angus Scale score recorded on Day -1.

    Measured: From baseline up to week 5

  9. Change From Baseline in Barnes Akathisia Rating Scale (BARS) Total Score

    The BARS for akathisia is a rating scale used to assess the severity of drug-induced akathisia, or restlessness, involuntary movements and inability to sit still. The range of scores is 0 to 14, with higher scores indicating greater severity. Baseline is defined as the BARS score recorded on Day -1.

    Measured: From baseline up to week 5

  10. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score

    The AIMS is a rating scale that is used to measure involuntary movements known as tardive dyskinesia, which can sometimes develop as a side effect of long-term treatment with antipsychotic medications. This measurement was a 12-item scale to assess orofacial, extremity, and truncal movements as well as the overall severity, incapacitation, and the participant's level of awareness of the movements. Items are scored from 0 (none) to 4 (severe). A higher score indicates more severe dyskinesia. Baseline is defined as the AIMS score recorded on Day -1. The total score is the sum of sub scores for items 1-7. The first 7 items are used to measure the severity of abnormal movements in the orofacial region (4 items: facial muscles, lips, jaw, tongue), upper extremities (1 item), lower extremities (1 item), and trunk (1 item). Change from baseline for the total scores are reported.

    Measured: From baseline up to week 5

  11. Number of Participants Who Experienced Weight Change

    The number of participants who lost weight, maintained their weight, or gained weight between baseline and week 5. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

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

    The change in Body Mass Index (BMI) from baseline up to week 5. BMI is a person's weight in kilograms divided by the square of height in meters. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

  13. Change From Baseline in Waist Circumference

    The change in waist circumference in centimeters from baseline up to week 5. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

  14. Change From Baseline in Orthostatic Vital Signs - Blood Pressure

    The change from baseline in orthostatic diastolic and systolic blood pressure measured while supine and standing after 2 minutes. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

  15. Change From Baseline in Orthostatic Vital Signs - Heart Rate

    The change from baseline in orthostatic heart rate measured while supine and standing after 2 minutes. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

  16. Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate

    The change from baseline up to Day 35 or early termination in ECG mean heart rate. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to Day 35 or early termination

  17. Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results

    The number of participants experiencing clinically significant abnormal physical examination results. Baseline is defined as measurements taken at screening.

    Measured: From baseline up to week 5

  18. Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS)

    C-SSRS assesses suicidal behavior and ideation on a scale with 4 general categories: suicidal ideation, intensity of ideation, suicidal behavior, and actual attempts. C-SSRS comprehensively identifies suicidal events while limiting the over identification of suicidal behavior. The C-SSRS was administered by a trained rater at the site.

    This study used 2 versions of the C-SSRS. At the Screening Visit, the "Lifetime" version was completed; for all subsequent visits, the "Since Last Visit" version of the C-SSRS was administered.

    Risk for suicidal behavior during the study was determined by the investigator's clinical assessment and C-SSRS as confirmed by the following:

    • Answering "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episode occurring within the 2 months before screening, or
    • Answering "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before screening. Non-suicidal, self-injurious behavior is not exclusionary.

    Measured: From screening up to Day 42

  19. Area Under the Plasma Concentration-Time Curve (AUC)

    AUC is the total area under the plasma drug concentration-time curve from time zero to 12 hours after drug administration. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

    Measured: At days 8 and 28

  20. Maximum Concentration (Cmax)

    Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

    Measured: At days 8 and 28

  21. Time to Maximum Concentration (Tmax)

    Tmax is defined as the time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

    Measured: At days 8 and 28

  22. Mean Observed Hemoglobin Levels

    The mean observed Hemoglobin levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    Male: 138 - 172 g/L Female: 121 - 151 g/L

    Measured: From baseline up to Days 21, 35, or early temination

  23. Mean Observed Hematocrit Levels

    The mean observed Hematocrit levels are displayed in percentages as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    Male: 40.7 - 50.3% Female: 36.1 - 44.3%

    Measured: From baseline up to Days 21, 35, or early temination

  24. Mean Observed Erythrocyte Levels

    The mean observed erythrocyte levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    Male: 4.7 - 6.1 10^12 cells/L Female: 4.2 - 5.4 10^12 cells/L

    Measured: From baseline up to Days 21, 35, or early temination

  25. Mean Observed Platelets Levels

    The mean observed platelet levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    150-450 10^9 cells/L

    Measured: From baseline up to Days 21, 35, or early temination

  26. Mean Observed Leukocytes Levels

    The mean observed leukocytes levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    4.5-10 10^9 cells/L

    Measured: From baseline up to Days 21, 35, or early temination

  27. Mean Observed Lymphocytes Levels

    The mean observed lymphocytes levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Reference Range:

    1-4.8 10^9 cells/L

    Measured: From baseline up to Days 21, 35, or early temination

  28. Mean Observed Activated Partial Thromboplastin Time

    The mean observed activated partial thromboplastin times in seconds are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Measured: From baseline up to Days 21, 35, or early temination

  29. Mean Observed Prothrombin Time

    The mean observed prothrombin times are displayed as measured at the specified timepoints. Baseline is defined as first dose.

    Measured: From baseline up to Days 21, 35, or early temination

  30. Mean Observed Urinalysis - pH

    The mean observed pH of participants' urine are displayed as measured at the specified timepoints. Baseline is defined as first dose. Urinalysis was completed using dipstick. Urinalysis was not completed if the local dipstick was normal.

    Measured: From baseline up to Days 21, 35, or early temination

  31. Mean Observed Urinalysis - Prolactin

    The mean observed prolactin levels of participants' urine are displayed as measured at the specified timepoints. Baseline is defined as first dose. Urinalysis was not completed if the local dipstick was normal.

    Measured: From baseline up to Days 21, 35, or early temination

  32. The Number of Participants With Positive Drug Screen Results

    A National Institute on Drug Abuse-5 urine drug screen (cannabinoids or marijuana, phencyclidine, amphetamines, opiates, and cocaine) was performed at screening and at baseline (Visit 2a [Day -1]). If a participant left the study site, they were to have a urine drug screen and test for alcohol (breathalyzer or urine alcohol level) upon returning to the study site.

    Measured: At screening, at Dat -1, and upon return from departure from study site at any time up to Day 42

  33. The Number of Participants With Elevated Liver Function Test Results

    The liver function test results (ALT, AST, ALP, total bilirubin, GGT) were specifically monitored to watch for any participants who met the FDA drug-induced liver injury (DILI) criteria. A summary of elevated liver function test results by visit is provided. Baseline is defined as measurements taken at screening.

    Monitoring for DILI criteria includes close observation initiated with ALT or AST >3 × ULN; discontinuation of treatment should be considered if ALT or AST >8 × ULN, ALT or AST >5 × ULN for more than 2 weeks, ALT or AST >3 × ULN and (total bilirubin >2 × ULN or international normalized ratio >1.5), or ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia (>5%).

    Measured: From screening up to Day 42

Timeline

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

  1. First posted4 Feb 2021
  2. Study start6 Apr 2021
  3. Primary completion29 Nov 2022
  4. Study completion7 Dec 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
256 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04738123
Sponsor's protocol ID
KAR-009
Status last verified
Dec 2024
First submitted
1 Feb 2021
Last updated
9 Dec 2024
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, Walling DP, Tamminga CA, Breier A, Zhu H, Miller AC, Paul SM, Brannan SK. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Aug 1;81(8):749-756. doi: 10.1001/jamapsychiatry.2024.0785.

    PubMed 38691387

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 32 sites in 2 countries.

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 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Ukraine. 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 9 Dec 2024). 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: From baseline up to 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 NCT04738123, 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 9 Dec 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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