A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia

NCT ID: NCT05919823

Last Updated: 2025-12-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-29

Study Completion Date

2024-12-09

Brief Summary

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A Phase 3, Multicenter, Two-part Study with a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects with DSM-5 Schizophrenia

Detailed Description

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Conditions

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Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo Capsules

KarXT

Group Type EXPERIMENTAL

Xanomeline and Trospium Chloride Capsules

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Placebo

Placebo Capsules

Intervention Type DRUG

Other Intervention Names

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KarXT

Eligibility Criteria

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Inclusion Criteria

1. Subject is Chinese national, aged 18 to 65 years, inclusive, at screening.
2. Subject is capable of providing written informed consent.
3. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 and MINI.
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 at screen.
2. If already an inpatient at screening, hospitalization has to be ≤2 weeks for the current exacerbation at the time of screening.
5. PANSS total score between 80 and 120,inclusive, with a scores 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 able to be confined to an inpatient setting for the duration of the 5-week double-blind part of the study, follow instructions, and comply with the protocol requirements.
11. Body mass index of 18 to 40 kg/m2, inclusive.
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. An informant is needed at the screening and baseline visits as well as at the end of the study for relevant assessments (site staff may act as informant while the subject is an inpatient). An informant may not be necessary if the subject has been a patient of the investigator for ≥1 year.
14. Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP must be willing and able to adhere to the contraception guidelines.

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. 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 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 C-SSRS.
8. Clinically significant abnormal findings on the physical examination, medical history, electrocardiogram, or clinical laboratory results at screening that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
9. Subjects are receiving or have recently received (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (e.g., lamotrigine, valproate); tricyclic antidepressants (e.g., imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate).
10. Subjects are receiving or have recently received (within 1 week before baseline \[Day -1\]) metformin.
11. Pregnant, lactating, or less than 3 months postpartum.
12. 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. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.
14. 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 has required clozapine within the last 12 months.
15. Subjects with prior exposure to KarXT.
16. Subjects who experienced any significant adverse effects due to trospium chloride.
17. Participation in another clinical study within 3 months before screening in which the subject received an experimental or investigational drug agent.
18. Significant risk of violent or destructive behavior.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zai Lab (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Karuna Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Anhui Mental Health Center

Hefei, Anhui, China

Site Status

Wuhu Hospital of Beijing Anding Hospital

Wuhu, Anhui, China

Site Status

Beijing Anding Hospital Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Peking University Sixth Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing HuiLongGuan Hospital

Changping, Beijing Municipality, China

Site Status

Chongqing 11th People's Hospital

Chongqing, Chongqing Municipality, China

Site Status

Chongqing Mental Health Center

Jiangbei, Chongqing Municipality, China

Site Status

The Affiliated Brain Hospital of Guangzhou Medical University

Guanzhou, Guangdong, China

Site Status

The Sixth People's Hosptial of Hebei Province

Baoding, Hebei, China

Site Status

Daqing City Third Hospital

Daqing, Heilongjiang, China

Site Status

Zhumadian Second People's Hospital

Zhumadian, Henan, China

Site Status

Wuhan Mental Health Center

Wuhan, Hubei, China

Site Status

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

Wuxi Mental Health Center

Wuxi, Jiangsu, China

Site Status

Jiangxi Mental Health Center

Nanchang, Jiangxi, China

Site Status

Mental Health Center of Xi'an City

Xi'an, Shaanxi, China

Site Status

Shandong Mental Health Center

Jinan, Shandong, China

Site Status

Shandong Daizhuang Hospital

Jining, Shandong, China

Site Status

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, China

Site Status

The Fourth People's Hospital of Chengdu

Chengdu, Sichuan, China

Site Status

Guangyuan Mental Health Center

Guangyuan, Sichuan, China

Site Status

Tianjin Anding Hospital

Tianjin, Tianjin Municipality, China

Site Status

Urumqi Fourth People's Hospital

Ürümqi, Xinjiang, China

Site Status

Hangzhou Seventh People's Hospital

Hangzhou, Zhejiang, China

Site Status

HuZhou Third Municipal Hospital

Huzhou, Zhejiang, China

Site Status

Ningbo Kangning Hospital

Ningbo, Zhejiang, China

Site Status

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status

Countries

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China

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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ZL-2701-001

Identifier Type: OTHER

Identifier Source: secondary_id

CN012-0063

Identifier Type: -

Identifier Source: org_study_id