An Extension Study to Assess Long-Term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Schizophrenia Clinical Trial

Official title:

An Open-label Extension Study to Assess the Long-term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05304767
• Other study ID #: KAR-013
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: March 7, 2022
• Est. completion date: February 2026

Study information

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

Clinical Trial Summary

This is a Phase 3, multicenter, 52-week, outpatient, open-label extension (OLE) study to evaluate the long-term safety and tolerability of adjunctive KarXT in subjects with schizophrenia with an inadequate response to their current antipsychotic treatment who previously completed the treatment period (Visit 8/Day 42 ± 3) of ARISE Study (KAR-012). The primary objective of the study is to assess the long-term safety and tolerability of adjunctive KarXT (a fixed dose combination of xanomeline and trospium chloride twice daily [BID]) in subjects with schizophrenia.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 280
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

1. Subject is aged =18 to <60 years at the time of randomization of Study KAR-012

2. Subject has successfully completed the treatment period of Study KAR-012

3. Subject has been compliant with the procedures in Study KAR-012 (in the Investigator's judgement)

4. Subject has been compliant with their background antipsychotic drug in Study KAR-012 in the opinion of the Investigator and based on subject and informant reporting Note: Subjects are required to remain on the same appropriate approved APD as in Study KAR-012 and should stay on that same dose throughout the study.

5. Subject is capable of providing signed Informed Consent Form before any study assessments will be performed

6. Subject resides in a stable living situation, in the opinion of the Investigator

7. Subject has identified a reliable informant/caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant can complete the study visits assessments via phone (as per local regulations). In Bulgaria, the informant needs to be physically present at all study visits where the Investigator determines that his/her input would be beneficial.

8. Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. A female subject is considered to be a WOCP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).

Exclusion Criteria:

1. Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or Columbia-Suicide Severity Rating Scale (C-SSRS) as

confirmed by the following:

1. Subject answers "Yes" to "suicidal ideation" Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS

2. Non-suicidal self-injurious behavior is not exclusionary

2. Any clinically significant abnormalities, including any finding(s) from ECG, or laboratory test at Visit 6, and the physical examination, vital signs, at the EOT visit of Study KAR-012 that the Investigator, in consultation with the Medical Monitor are considered to jeopardize the safety of the subject

3. Female subject is pregnant

4. If, in the opinion of the Investigator (and/or Sponsor/ Medical Monitor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator (and/or Sponsor /Medical Monitor), may compromise the safety of the subject or affect their ability to adhere to the protocol visit schedule or study requirements

5. Risk of violent or destructive behavior as per Investigator's judgement

6. Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study

7. History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator

8. Subject is taking, or plans to take while in the study, any prohibited concomitant medication

9. For all male subjects only, any one of the following:

1. History of bladder stones

2. History of recurrent urinary tract infections

3. Serum prostate specific antigen (PSA) >10 ng/mL

4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6

5. A sum of scores on IPSS items 1, 3, 5, and 6 of =9 Note: IPSS will be required only for male subjects = 45 years of age. Subjects already enrolled in the study who do not have available PSA values from Study KAR-012 for baseline value use in Study KAR-013, will have these assessments at their next clinic visit planned after re-consenting to determine current eligibility.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Xanomeline and Trospium Chloride Capsules
KarXT 50 mg/20 mg BID KarXT 75mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID

Locations

Country	Name	City	State
Bulgaria	Clinical Trial Site	Kazanlak
Bulgaria	Clinical Trial Site	Sofia
Bulgaria	Clinical Trial Site	Varna
Serbia	Clinical Trial Site	Kragujevac
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Austin	Texas
United States	Clinical Trial Site	Bellevue	Washington
United States	Clinical Trial Site	Bellflower	California
United States	Clinical Trial Site	Cerritos	California
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Decatur	Georgia
United States	Clinical Trial Site	Garden Grove	California
United States	Clinical Trial Site	Hialeah	Florida
United States	Clinical Trial Site	Irving	Texas
United States	Clinical Trial Site	Lafayette	California
United States	Clinical Trial Site	Las Vegas	Nevada
United States	Clinical Trial Site	Lemon Grove	California
United States	Clinical Trial Site	Little Rock	Arkansas
United States	Clinical Trial Site	Miami Lakes	Florida
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	Staten Island	New York
United States	Clinical Trial Site	Tamarac	Florida
United States	Clinical Trial Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Karuna Therapeutics

Countries where clinical trial is conducted

United States,  Bulgaria,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)		From initial dose to safety follow-up visit (54 weeks) or early termination
Secondary	Incidence of serious treatment-emergent adverse events (TEAEs)		From initial dose to safety follow-up visit (54 weeks) or early termination
Secondary	Incidence of TEAEs leading to discontinuation of study drug		From initial dose to safety follow-up visit (54 weeks) or early termination