Clinical trial NCT04659161: A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Schizophrenia; Psychosis
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 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.

Primary outcomes:
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
timeFrame: Baseline and Week 5
Secondary outcomes:
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5
timeFrame: Baseline and Week 5
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5
timeFrame: Baseline and Week 5
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score
timeFrame: Baseline and Week 5
measure: Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5
timeFrame: Baseline and Week 5
measure: Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5
timeFrame: Baseline and Week 5
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Bellflower
country: United States
facility: CITrials
state: California
city: Culver City
country: United States
facility: ProScience Research Institute
state: California
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Long Beach
country: United States
facility: CNS Network
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Pico Rivera
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Miami Lakes
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Lincolnwood
country: United States
facility: Pillar Clinical Research
state: Illinois
city: Saint Louis
country: United States
facility: Arch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research
state: Ohio
city: Austin
country: United States
facility: Community Clinical Research
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research
state: Texas
Study officials:
affiliation: Karuna Therapeutics
name: Inder Kaul, MD
role: STUDY_DIRECTOR
References: