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

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04820309
• Other study ID #: CN012-0007
• Secondary ID: CN012-0007KAR-01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: June 2024
• Source: Karuna Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 568
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

2. Subject is capable of providing informed consent.

1. A signed informed consent form (ICF) must be provided before any study assessments are performed.

2. Subject must be fluent in (oral and written) the language of the ICGF to consent.

3. 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.

4. 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.

5. PANSS total score = 80 at screening and Baseline Visit B (Day 0).

6. Clinical Global Impression - Severity (CGI-S) score of = 4 at screening and Baseline Visit B (Day 0).

7. At the time of screening, or at any time within the 30 days prior to screening, the subject must have received an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.

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

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

10. 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.

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

12. 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 0.

13. Body mass index must be = 18 and = 40 kg/m2.

14. 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.

15. 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 or a positive urine drug screen (UDS) for a substance other than cannabis at screening or baseline.

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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.

Locations

Country	Name	City	State
Puerto Rico	INSPIRA Clinical Research	San Juan
United States	Advanced Research Center; Inc.	Anaheim	California
United States	Michigan Clinical Research Institute PC	Ann Arbor	Michigan
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Synexus Clinical Research US; Inc.	Atlanta	Georgia
United States	BioBehavioral Research of Austin P.C.	Austin	Texas
United States	Community Clinical Research Inc.	Austin	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	CiTrials	Bellflower	California
United States	Clinical Innovations; Inc. DBA Citrials	Bellflower	California
United States	Hassman Research Institute	Berlin	New Jersey
United States	Synexus Clinical Research US; Inc.	Cerritos	California
United States	Uptown Research Institute	Chicago	Illinois
United States	Local Institution - 011-247	Costa Mesa	California
United States	Proscience Research Group	Culver City	California
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	iResearch Atlanta; LLC	Decatur	Georgia
United States	InSite Clinical Research; LLC	DeSoto	Texas
United States	Cedar Clinical Research	Draper	Utah
United States	Core Clinical Research	Everett	Washington
United States	Precise Research Centers	Flowood	Mississippi
United States	North Texas Clinical Trials	Fort Worth	Texas
United States	Psychiatric Consultants	Franklin	Tennessee
United States	CBH Health; LLC	Gaithersburg	Maryland
United States	CNS Network	Garden Grove	California
United States	Behavioral Research Specialists; LLC	Glendale	California
United States	Velocity Clinical Research; Hallandale Beach	Hallandale Beach	Florida
United States	Local Institution - 011-228	Hickory	North Carolina
United States	Cenexel RCA (Research Centers of America)	Hollywood	Florida
United States	Omega Clinical Trials	La Habra	California
United States	Altea Research Institute	Las Vegas	Nevada
United States	Woodland International Research Group	Little Rock	Arkansas
United States	Alliance for Wellness dba Alliance for Research	Long Beach	California
United States	Hassman Research Institute	Marlton	New Jersey
United States	Central Miami Medical Institute	Miami	Florida
United States	Phoenix Medical Research	Miami	Florida
United States	Premier Clinical Research Institute	Miami	Florida
United States	Innovative Clinical Research; Inc.	Miami Lakes	Florida
United States	Global Medical Institutes LLC Scranton Medical Institute	Moosic	Pennsylvania
United States	Manhattan Behavioral Medicine PLLC	New York	New York
United States	The Medical Research Network; LLC	New York	New York
United States	Neuro-Behavioral Clinical Research	North Canton	Ohio
United States	Excell Research Inc	Oceanside	California
United States	Local Institution - 011-225	Oceanside	California
United States	Health Synergy Clinical Research	Okeechobee	Florida
United States	SP Research PLLC	Oklahoma City	Oklahoma
United States	NRC Research Institute	Orange	California
United States	Pines Care Research Center Inc.	Pembroke Pines	Florida
United States	CNRI-Los Angeles LLC	Pico Rivera	California
United States	healthTx	Richmond	Texas
United States	Clinical Innovations	Riverside	California
United States	Finger Lakes clinical	Rochester	New York
United States	Woodland Research Northwest	Rogers	Arkansas
United States	St. Charles Psychiatric Associates/Midwest Research Group	Saint Charles	Missouri
United States	Arch Clinical Trials LLC	Saint Louis	Missouri
United States	Siyan Clinical Research	Santa Rosa	California
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Louisiana Clinical Research	Shreveport	Louisiana
United States	CNS Network	Torrance	California
United States	CincyScience	West Chester	Ohio
United States	Suburban Research Associates	West Chester	Pennsylvania
United States	NeuroScience Research Institute	West Palm Beach	Florida
United States	Ascension Via Christi Research	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Karuna Therapeutics

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)	The number and percentage of participants with TEAEs will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Incidence of serious TEAEs	The number and percentage of participants with serious TEAEs will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Incidence of TEAEs leading to withdrawal	The number and percentage of participants with TEAEs leading to withdrawal will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at 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.	Week 52
Secondary	Change From Baseline in PANSS Positive Score at 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.	Week 52
Secondary	Change From Baseline in PANSS Negative Score at 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.	Week 52
Secondary	Change From Baseline in PANSS Negative Marder Factor Score	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.	Week 52
Secondary	Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at 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.	Week 52
Secondary	Percentage of PANSS responders (a 30% change in PANSS total score) at 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.	Week 52

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting