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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified October 2023 by Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Sponsor
Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Information Provided by (Responsible Party)
Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Clinicaltrials.gov Identifier
NCT04659161
Other Study ID Numbers:
KAR-007
First Submitted
December 1, 2020
First Posted
December 8, 2020
Results First Posted
October 26, 2023
Last Update Posted
December 11, 2023
Last Verified
October 2023

ClinicalTrials.gov processed this data on November 2023. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
SchizophreniaSchizophrenia; Psychosis
Drug: Xanomeline and Trospium Chloride CapsulesDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment252 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA 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
Study Start DateDecember 15, 2020
Actual Primary Completion DateMay 23, 2022
Actual Study Completion DateMay 23, 2022

Groups and Cohorts

Group/CohortIntervention/Treatment
KarXT
Drug: Xanomeline and Trospium Chloride Capsules
Oral xanomeline 50 mg/trospium chloride 20 mg BID (twice a day) for the first 2 days (Days 1 and 2) followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the subject was continuing to experience adverse events (AEs) from the previous dose of KarXT 100/20 BID. All subjects who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.
Placebo
Drug: Placebo
Placebo Capsules twice a day (BID)

Outcome Measures

Primary Outcome Measures
  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
    The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
Secondary Outcome Measures
  1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5
    The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
  2. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5
    The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
  3. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score
    The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
  4. Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5
    The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants.
  5. Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5
    The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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 30 days after the last dose of study drug. Sperm donation is not allowed for 30 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.

Contacts and Locations

Sponsors and CollaboratorsKaruna Therapeutics, Inc., a Bristol Myers Squibb company
Locations
Woodland International Research Group, LLC | Little Rock Arkansas, United States, 72211CITrials | Bellflower California, United States, 90706ProScience Research Institute | Culver City California, United States, 90230California Clinical Trials Medical Group | Glendale California, United States, 91206Synergy San Diego | Lemon Grove California, United States, 91945CNS Network | Long Beach California, United States, 90806Catalina Research Institute, LLC | Montclair California, United States, 91763NRC Research Institute | Orange California, United States, 92868California Neuropsychopharmacology Clinical Research Institute | Pico Rivera California, United States, 90660California Neuropsychopharmacology Clinical Research Institute | San Diego California, United States, 92101Schuster Medical Research Institute | Sherman Oaks California, United States, 91403Innovative Clinical Research, Inc. | Miami Lakes Florida, United States, 33016Research Centers of America | Oakland Park Florida, United States, 33334iResearch Atlanta, LLC | Decatur Georgia, United States, 30030Uptown Research Institute | Chicago Illinois, United States, 60640Pillar Clinical Research | Lincolnwood Illinois, United States, 60712Arch Clinical Trials | St Louis Missouri, United States, 63118Altea Research Institute | Las Vegas Nevada, United States, 89102Hassman Research Institute | Marlton New Jersey, United States, 08053Neuro-Behavioral Clinical Research | North Canton Ohio, United States, 44720Community Clinical Research | Austin Texas, United States, 78754Pillar Clinical Research | Richardson Texas, United States, 75080
Investigators
Study Director: Inder Kaul, MD, Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Study Documents (Full Text)
Documents provided by Karuna Therapeutics, Inc., a Bristol Myers Squibb company: Study Protocol  August 8, 2021Documents provided by Karuna Therapeutics, Inc., a Bristol Myers Squibb company: Statistical Analysis Plan  June 27, 2022