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

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ClinicalTrials.gov Identifier: NCT04659161
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
Karuna Therapeutics

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizophrenia; Psychosis Drug: Xanomeline and Trospium Chloride Capsules Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 246 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 16, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: KarXT Drug: Xanomeline and Trospium Chloride Capsules
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 Name: KarXT

Placebo Comparator: Placebo Drug: Placebo
Placebo Capsules




Primary Outcome Measures :
  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5 [ Time Frame: 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 decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.


Secondary Outcome Measures :
  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5 [ Time Frame: Week 5 ]
    The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. 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.

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

  3. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score [ Time Frame: Week 5 ]
    The Negative Marder Factor score is derived from the 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.

  4. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 5 [ Time Frame: 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.

  5. Percentage of Positive and Negative Syndrome Scale (PANSS) responders (a 30% change in PANSS total score) at Week 5 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is aged 18 to 65 years, inclusive, at screening.
  2. Subject is capable of providing informed consent.

    1. A signed informed consent form must be provided before any study assessments are performed.
    2. Subject must be fluent (oral and written) in English to consent
  3. 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.
  4. Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.

    1. The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.
    2. If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.
  5. 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:

    1. Item 1 (P1; delusions)
    2. Item 2 (P2; conceptual disorganization)
    3. Item 3 (P3; hallucinatory behavior)
    4. Item 6 (P6; suspiciousness/persecution)
  6. Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%.
  7. Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.
  8. 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).
  9. 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).
  10. Subject is willing and able to be confined to an inpatient setting for the study duration, follow instructions, and comply with the protocol requirements.
  11. BMI must be ≥18 and ≤40 kg/m2.
  12. 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.
  13. Subject has an identified reliable informant.
  14. 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 7 days after the last dose of study drug. Sperm donation is not allowed for 7 days after the final dose of study drug.

Exclusion Criteria:

  1. 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.
  2. Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
  3. 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.
  4. 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.
  5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
  6. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
  7. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
  8. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening.
  9. 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).
  10. Pregnant, lactating, or less than 3 months postpartum.
  11. 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.
  12. Positive test for coronavirus (COVID-19) within 2 weeks before screening and at screening.
  13. Subjects with extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.
  14. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.
  15. 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.
  16. Subjects with prior exposure to KarXT.
  17. Subjects who experienced any adverse effects due to xanomeline or trospium.
  18. Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before screening.
  19. Risk of violent or destructive behavior.
  20. Current involuntary hospitalization or incarceration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04659161


Contacts
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Contact: Stephen Brannan, MD 857-449-2234 sbrannan@karunatx.com

Locations
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United States, California
Synergy San Diego Recruiting
Lemon Grove, California, United States, 91945
United States, Florida
Innovative Clinical Research, Inc. Recruiting
Miami Lakes, Florida, United States, 33016
United States, Georgia
iResearch Atlanta, LLC Recruiting
Decatur, Georgia, United States, 30030
United States, Illinois
Pillar Clinical Research Recruiting
Lincolnwood, Illinois, United States, 60712
United States, Nevada
Altea Research Institute Recruiting
Las Vegas, Nevada, United States, 89102
United States, New Jersey
Hassman Research Institute Recruiting
Marlton, New Jersey, United States, 08053
United States, Texas
Pillar Clinical Research Recruiting
Richardson, Texas, United States, 75080
Sponsors and Collaborators
Karuna Therapeutics
Investigators
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Study Director: Inder Kaul, MD Karuna Therapeutics
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Responsible Party: Karuna Therapeutics
ClinicalTrials.gov Identifier: NCT04659161    
Other Study ID Numbers: KAR-007
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Xanomeline
Trospium chloride
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Urological Agents
Parasympathomimetics
Psychotropic Drugs
Muscarinic Agonists
Cholinergic Agonists