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

Schizophrenia Clinical Trial

— UNITE-001  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05919823
• Other study ID #: ZL-2701-001
• Status: Recruiting
• Phase: Phase 3
• Start date: May 29, 2023
• Est. completion date: May 2025

Study information

• Verified date: May 2024
• Source: Karuna Therapeutics
• Contact: Clare Qu
• Phone: 861861817461
• Email: ZaiLab_2701-001StudyTeam[@]zailaboratory.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

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 8-35 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.
• Placebo
Placebo Capsules

Locations

Country	Name	City	State
China	The Sixth People's Hosptial of Hebei Province	Baoding	Hebei
China	Beijing Anding Hospital Capital Medical University	Beijing	Beijing
China	Peking University Sixth Hospital	Beijing	Beijing
China	Beijing HuiLongGuan Hospital	Changping	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The Fourth People's Hospital of Chengdu	Chengdu	Sichuan
China	Chongqing 11th People's Hospital	Chongqing	Chongqing
China	Daqing City Third Hospital	Daqing	Heilongjiang
China	Guangyuan Mental Health Center	Guangyuan	Sichuan
China	The Affiliated Brain Hospital of Guangzhou Medical University	Guanzhou	Guangdong
China	Hangzhou Seventh People's Hospital	Hangzhou	Zhejiang
China	Anhui Mental Health Center	Hefei	Anhui
China	HuZhou Third Municipal Hospital	Huzhou	Zhejiang
China	Chongqing Mental Health Center	Jiangbei	Chongqing
China	Shandong Mental Health Center	Jinan	Shandong
China	Shandong Daizhuang Hospital	Jining	Shandong
China	Jiangxi Mental Health Center	Nanchang	Jiangxi
China	Ningbo Kangning Hospital	Ningbo	Zhejiang
China	Shanghai Mental Health Center	Shanghai	Shanghai
China	The First Hospital of Hebei Medical University	Shijia Zhuang	Hebei
China	Tianjin Anding Hospital	Tianjin	Tianjin
China	Urumqi Fourth People's Hospital	Ürümqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Wuhan Mental Health Center	Wuhan	Hubei
China	Wuhu Hospital of Beijing Anding Hospital	Wuhu	Anhui
China	Wuxi Mental Health Center	Wuxi	Jiangsu
China	Mental Health Center of Xi'an City	Xi'an	Shaanxi
China	Zhumadian Second People's Hospital	Zhumadian	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Karuna Therapeutics	Zai Lab (Shanghai) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline 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 decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Baseline and Week 5
Secondary	Change from baseline in PANSS positive symptom score at Week 5	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.	Baseline and Week 5
Secondary	Change from baseline in PANSS negative symptom score at Week 5	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.	Baseline and Week 5
Secondary	Change from baseline in PANSS Negative Marder Factor score at Week 5	The Negative Marder Factor score is derived from the PANSS and consists of the sum of 5 negative symptom items (N) and 2 general symptom items (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.	Baseline and Week 5
Secondary	Change from baseline in 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.	Baseline and Week 5
Secondary	Percentage of PANSS responders (defined as a =30% change in PANSS total score from baseline) at Week 5	A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.	Baseline and Week 5