Clinical trial NCT05919823: A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Zai Lab (Shanghai) Co., Ltd.
First posted: 2023-06-26
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in PANSS total score at Week 5
timeFrame: Baseline and Week 5
Secondary outcomes:
measure: Change from baseline in PANSS positive symptom score at Week 5
timeFrame: Baseline and Week 5
measure: Change from baseline in PANSS negative symptom score at Week 5
timeFrame: Baseline and Week 5
measure: Change from baseline in PANSS Negative Marder Factor score at Week 5
timeFrame: Baseline and Week 5
measure: Change from baseline in CGI-S score at Week 5
timeFrame: Baseline and Week 5
measure: Percentage of PANSS responders (defined as a ≥30% change in PANSS total score from baseline) at Week 5
timeFrame: Baseline and Week 5
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Mental Health Center
state: Anhui
city: Wuhu
country: China
facility: Wuhu Hospital of Beijing Anding Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Anding Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Sixth Hospital
state: Beijing
city: Changping
country: China
facility: Beijing HuiLongGuan Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing 11th People's Hospital
state: Chongqing
city: Jiangbei
country: China
facility: Chongqing Mental Health Center
state: Chongqing
city: Guanzhou
country: China
facility: The Affiliated Brain Hospital of Guangzhou Medical University
state: Guangdong
city: Baoding
country: China
facility: The Sixth People's Hosptial of Hebei Province
state: Hebei
city: Daqing
country: China
facility: Daqing City Third Hospital
state: Heilongjiang
city: Zhumadian
country: China
facility: Zhumadian Second People's Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Mental Health Center
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Wuxi
country: China
facility: Wuxi Mental Health Center
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Mental Health Center
state: Jiangxi
city: Xi'an
country: China
facility: Mental Health Center of Xi'an City
state: Shaanxi
city: Jinan
country: China
facility: Shandong Mental Health Center
state: Shandong
city: Jining
country: China
facility: Shandong Daizhuang Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
city: Chengdu
country: China
facility: The Fourth People's Hospital of Chengdu
state: Sichuan
city: Guangyuan
country: China
facility: Guangyuan Mental Health Center
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Anding Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Urumqi Fourth People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Hangzhou Seventh People's Hospital
state: Zhejiang
city: Huzhou
country: China
facility: HuZhou Third Municipal Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Kangning Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: