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An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-5)

Sponsor
Karuna Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04820309
Collaborator
(none)
400
Enrollment
45
Locations
1
Arm
24.9
Anticipated Duration (Months)
8.9
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 3, multicenter, 56-week, outpatient, open-label (OL) study to evaluate the long-term safety, tolerability, and efficacy of KarXT in de novo subjects with Diagnostic and Statistical Manual-Fifth Edition (DSM-5) schizophrenia. In this OL study, all subjects will receive KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) for up to 52 weeks. The primary objective of the study is to assess the long-term safety and tolerability of KarXT in subjects with a DSM-5 diagnosis of schizophrenia. The secondary objective of this study is to assess the long-term efficacy and characterize the pharmacokinetics of xanomeline and trospium after administration of KarXT.

Condition or Disease Intervention/Treatment Phase
  • Drug: Xanomeline and Trospium Chloride Capsules
 Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in De Novo Subjects With DSM-5 Schizophrenia
Actual Study Start Date :
Jun 2, 2021
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Jul 1, 2023

Arms and Interventions

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 8-364 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. Re-escalation to 125/30 BID or re-titration in cases in which the subject has been off KarXT for a longer period of time (at least a week) is allowed and will require a discussion between the principal investigator and the medical monitor.
Other Names:
  • KarXT

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of treatment-emergent adverse events (TEAEs) [From initial dose through 7 days after the final dose (up to 53 weeks)]

      The number and percentage of participants with TEAEs will be determined

    Secondary Outcome Measures

    1. Incidence of serious TEAEs [From initial dose through 7 days after the final dose (up to 53 weeks)]

      The number and percentage of participants with serious TEAEs will be determined

    2. Incidence of TEAEs leading to withdrawal [From initial dose through 7 days after the final dose (up to 53 weeks)]

      The number and percentage of participants with TEAEs leading to withdrawal will be determined

    3. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52 [Week 52]

      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.

    4. Change From Baseline in PANSS Positive Score at Week 52 [Week 52]

      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.

    5. Change From Baseline in PANSS Negative Score at Week 52 [Week 52]

      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.

    6. Change From Baseline in PANSS Negative Marder Factor Score [Week 52]

      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.

    7. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 52 [Week 52]

      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.

    8. Percentage of PANSS responders (a 30% change in PANSS total score) at Week 52 [Week 52]

      A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 52.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Subject is aged 18 to 65 years at screening.

    2. Subject is capable of providing informed consent.

    3. A signed informed consent form must be provided before any study assessments are performed.

    4. Subject must be fluent in (oral and written) English to consent.

    5. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.

    6. Subject has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 8 weeks of screening and is psychiatrically stable in the opinion of the investigator.

    7. PANSS total score ≤ 80 at screening.

    8. Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening

    9. At screening, subject is receiving an oral antipsychotic medication daily as maintenance therapy. Therapy must be stable, defined as the same oral antipsychotic medication for at least 8 weeks before screening and at the same dose for at least 4 weeks before screening.

    10. In the opinion of the investigator, it is clinically appropriate for the subject to discontinue current antipsychotic therapy and initiate experimental treatment with KarXT.

    11. Subject is willing and able, in the opinion of the investigator, to discontinue all antipsychotic medications prior to baseline visit.

    12. Subject has an identified reliable informant willing to be able to address some questions related to certain study visits, if needed. An informant may not be necessary if the subject has been the patient of the investigator for ≥1 year.

    13. At Day 0, subject will have been off lithium therapy for at least 2 weeks and must have discontinued all oral antipsychotic medications.

    14. Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for paliperidone palmitate) before Day

    16. Body mass index must be ≥ 18 and ≤ 40 kg/m2.

    17. Subject resides in a stable living situation and is anticipated to remain in a stable living situation for the duration of study enrollment, in the opinion of the investigator.

    18. Women of childbearing potential or men with sexual partners of childbearing potential must be willing and able to use at least 1 highly effective method of contraception during the study and for at least 30 days after the last dose of KarXT. Sperm donation is not allowed for 30 days after the final dose of KarXT.

    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).

    2. Subject has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months.

    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. Subject has 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.

    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 from the physical examination, medical history, ECG, or clinical laboratory results at screening.

    9. Subjects cannot currently (within 5 half-lives before Day 0) be receiving monoamine oxidase inhibitors, anticonvulsants, tricyclic antidepressants, centrally active anticholinergics, or any other psychoactive medications other than daily antipsychotic maintenance therapy. As-needed anxiolytics and/or sleep aids are permitted. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors taken at stable dose may be permitted.

    10. 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) within the past 12 months or having received clozapine within the past 3 years

    11. Pregnant, lactating, or less than 3 months postpartum.

    12. 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.

    13. Subjects has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening.

    14. Subject has extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.

    15. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 6 months before screening.

    16. Subject has prior exposure to KarXT.

    17. Risk of violent or destructive behavior.

    18. Current involuntary hospitalization or incarceration.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Woodland International Research Group Little Rock Arkansas United States 72211
    2 Woodland Research Northwest Rogers Arkansas United States 72758
    3 Advanced Research Center, Inc. Anaheim California United States 92805
    4 ATP Clinical Research, Inc. Costa Mesa California United States 92626
    5 ProScience Research Group Culver City California United States 90230
    6 Behavioral Clinical Research, Inc. Glendale California United States 91206
    7 Omega Clinical Trials La Habra California United States 90631
    8 Alliance for Wellness Long Beach California United States 90807
    9 Excell Research Inc Oceanside California United States 92056
    10 NRC Research Institute Orange California United States 92868
    11 CNRI-Los Angeles, LLC Pico Rivera California United States 90660
    12 CITrials Riverside California United States 92506
    13 CITrials Santa Ana California United States 92705
    14 Schuster Medical Research Institute Sherman Oaks California United States 91403
    15 Velocity Clinical Research, Hallandale Beach Hallandale Beach Florida United States 33009
    16 Homestead Research Institute, Inc. Homestead Florida United States 33030
    17 Innovative Clinical Research Miami Lakes Florida United States 33016
    18 Premier Clinical Research Institute Miami Florida United States 33122
    19 Central Miami Medical Institute Miami Florida United States 33125
    20 Phoenix Medical Research Miami Florida United States 33165
    21 Health Synergy Clinical Research Okeechobee Florida United States 34972
    22 Pines Care Research Center Pembroke Pines Florida United States 33024
    23 Atlanta Center for Medical Research Atlanta Georgia United States 30331
    24 Uptown Research Institute Chicago Illinois United States 60640
    25 Ascension Via Christi Research Wichita Kansas United States 67214
    26 Louisiana Clinical Research Shreveport Louisiana United States 71101
    27 CBH Health, LLC Gaithersburg Maryland United States 20877
    28 Michigan Clinical Research Institute PC Ann Arbor Michigan United States 48105
    29 Precise Research Centers Flowood Mississippi United States 39170
    30 Midwest Research Group - St. Charles Psychiatric Associates Saint Charles Missouri United States 63304
    31 St. Charles Psychiatric Associates/Midwest Research Group Saint Charles Missouri United States 63304
    32 Arch Clinical Trials Saint Louis Missouri United States 63118
    33 Altea Research Institute Las Vegas Nevada United States 89102
    34 Hassman Research Institute Berlin New Jersey United States 08009
    35 Manhattan Behavioral Medicine, PLLC New York New York United States 10036
    36 The Medical Research Network, LLC New York New York United States 10128
    37 Finger Lakes Clinical Research Rochester New York United States 14618
    38 Midwest Clinical Research Center Dayton Ohio United States 45417
    39 Cincy Science West Chester Ohio United States 45069
    40 Suburban Research Associates Media Pennsylvania United States 19063
    41 Community Clinical Research Austin Texas United States 78754
    42 BioBehavioral Research of Austin Austin Texas United States 78759
    43 InSite Clinical Research, LLC DeSoto Texas United States 75115
    44 Cedar Clinical Research Draper Utah United States 84020
    45 Northwest Clinical Research Center Bellevue Washington United States 98007

    Sponsors and Collaborators

    • Karuna Therapeutics

    Investigators

    • Study Director: Inder Kaul, MD, Karuna Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Karuna Therapeutics
    ClinicalTrials.gov Identifier:
    NCT04820309
    Other Study ID Numbers:
    • KAR-011
    First Posted:
    Mar 29, 2021
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Schizophrenia
    Xanomeline
    Trospium chloride

    Study Results

    No Results Posted as of Aug 15, 2022