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 #: CN012-0009
• Secondary ID: CN012-0009KAR-01
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: March 7, 2022
• Est. completion date: February 28, 2026

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, 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 28, 2026
• Est. primary completion date: February 28, 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 CN012-0009, 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	Local Institution - 318	Cherven Bryag
Bulgaria	Local Institution - 311	Dupnitsa
Bulgaria	Local Institution - 316	Kardzhali
Bulgaria	Local Institution - 302	Kazanlak
Bulgaria	Local Institution - 304	Novi Iskar
Bulgaria	Local Institution - 301	Pleven
Bulgaria	UMHAT 'Dr. Georgi Stranski', EAD	Pleven
Bulgaria	Local Institution - 314	Plovdiv
Bulgaria	Local Institution - 321	Plovdiv
Bulgaria	Local Institution - 313	Razgrad
Bulgaria	MHAT Dr Ivan Seliminski AD	Sliven
Bulgaria	Local Institution - 303	Sofia
Bulgaria	Local Institution - 305	Sofia
Bulgaria	Local Institution - 306	Sofia
Bulgaria	Local Institution - 307	Sofia
Bulgaria	Local Institution - 309	Sofia
Bulgaria	Local Institution - 320	Sofia
Bulgaria	Local Institution - 317	Targovishte
Bulgaria	DCC Mladost M - Varna, OOD	Varna
Bulgaria	Local Institution - 310	Vratsa
India	Local Institution - 604	Ahmedabad	Gujarat
India	Local Institution - 607	Ahmedabad	Gujarat
India	Local Institution - 615	Ajmer	Rajasthan
India	Local Institution - 610	Aurangabad	Maharashtra
India	Local Institution - 617	Belgavi	Karnataka
India	Local Institution - 616	Guwahati	Assam
India	Local Institution - 611	Kozhikode	Kerala
India	Local Institution - 612	Lucknow	Uttar Pradesh
India	Local Institution - 602	Mangalore	Karnataka
India	Local Institution - 614	Mangalore	Karnataka
India	Local Institution - 601	Mysore	Karnataka
India	Local Institution - 603	Nagpur	Maharashtra
India	Local Institution - 605	Nashik	Maharashtra
India	Local Institution - 608	Nashik	Maharashtra
India	Local Institution - 606	Rajkot	Rajasthan
India	Local Institution - 609	Surat	Gujarat
India	Local Institution - 613	Vadodara	Gujarat
Poland	Local Institution - 506	Bialystok
Poland	Local Institution - 507	Gdansk
Poland	Local Institution - 509	Grudziadz
Poland	Local Institution - 501	Kielce
Poland	Local Institution - 503	Lodz
Poland	Local Institution - 505	Lublin
Poland	Local Institution - 502	Siemianowice Slaskie
Poland	Local Institution - 508	Suchy Las
Poland	Local Institution - 504	Tuszyn
Romania	Local Institution - 803	Brasov
Romania	Local Institution - 802	Bucuresti
Romania	Local Institution - 804	Bucuresti
Romania	Local Institution - 807	Bucuresti
Romania	Local Institution - 809	Bucuresti
Romania	Local Institution - 810	Bucuresti
Romania	Local Institution - 808	Craiova
Romania	Local Institution - 801	Galati
Romania	Local Institution - 806	Iasi
Romania	Local Institution - 805	Sibiu
Serbia	Local Institution - 402	Belgrade
Serbia	Local Institution - 403	Belgrade
Serbia	Local Institution - 405	Belgrade
Serbia	Local Institution - 413	Belgrade
Serbia	Local Institution - 417	Belgrade
Serbia	Local Institution - 404	Kovin
Serbia	Local Institution - 414	Kovin
Serbia	Local Institution - 401	Kragujevac
Serbia	Local Institution - 406	Kragujevac
Serbia	Local Institution - 408	Kragujevac
Serbia	University Clinical Center Kragujevac	Kragujevac
Serbia	Local Institution - 411	Nis
Serbia	Local Institution - 415	Nis
Serbia	Local Institution - 410	Novi Knezevac
Serbia	Local Institution - 416	Novi Knezevac
Serbia	Local Institution - 409	Vrsac
United Kingdom	Local Institution - 706	Ashton Under Lyne	Lancashire
United Kingdom	Local Institution - 703	Birmingham	West Midlands
United Kingdom	Local Institution - 707	Bodmin	Cornwall
United Kingdom	Local Institution - 705	Brighton	East Sussex
United Kingdom	Local Institution - 702	Chertsey	Surrey
United Kingdom	Local Institution - 701	London	Greater London
United Kingdom	Local Institution - 708	Oxford	Oxfordshire
United Kingdom	Local Institution - 704	Paisley	Renfrewshire
United States	Advanced Research Center, Inc.	Anaheim	California
United States	Local Institution - 184	Ann Arbor	Michigan
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Synexus Clinical Research US, Inc.	Atlanta	Georgia
United States	Local Institution - 135	Augusta	Georgia
United States	Community Clinical Research, Inc.	Austin	Texas
United States	Local Institution - 163	Beachwood	Ohio
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	CITrials - Bellflower	Bellflower	California
United States	Local Institution - 158	Boston	Massachusetts
United States	Local Institution - 187	Boston	Massachusetts
United States	Synexus Clinical Research US, Inc.	Cerritos	California
United States	Local Institution - 142	Chicago	Illinois
United States	Local Institution - 177	Chicago	Illinois
United States	Uptown Research Institute, LLC	Chicago	Illinois
United States	Local Institution - 165	Cincinnati	Ohio
United States	Local Institution - 186	Coral Gables	Florida
United States	Local Institution - 167	Culver City	California
United States	CenExel iResearch Atlanta	Decatur	Georgia
United States	Local Institution - 141	Encino	California
United States	Local Institution - 179	Eugene	Oregon
United States	Local Institution - 166	Gaithersburg	Maryland
United States	Local Institution - 168	Garfield Heights	Ohio
United States	Local Institution - 149	Grand Rapids	Michigan
United States	Galiz Research, LLC	Hialeah	Florida
United States	Local Institution - 182	Hialeah	Florida
United States	Local Institution - 176	Hickory	North Carolina
United States	Local Institution - 180	Houston	Texas
United States	Local Institution - 183	Houston	Texas
United States	University Hills Clinical Research - Irving	Irving	Texas
United States	Local Institution - 162	Kalamazoo	Michigan
United States	Local Institution - 152	La Habra	California
United States	Sunwise Clinical Research, LLC.	Lafayette	California
United States	Altea Research Institute, Las Vegas	Las Vegas	Nevada
United States	Local Institution - 147	Las Vegas	Nevada
United States	Synergy Clinical Research of Escondido	Lemon Grove	California
United States	Local Institution - 175	Little Rock	Arkansas
United States	Woodland International Research Group, LLC	Little Rock	Arkansas
United States	CenExel Collaborative Neuroscience Research	Los Alamitos	California
United States	Local Institution - 169	Marietta	Georgia
United States	Local Institution - 105	Miami	Florida
United States	Local Institution - 120	Miami	Florida
United States	Premier Clinical Research Institute, Inc.	Miami	Florida
United States	Assertive Research Center	Miami Lakes	Florida
United States	Local Institution - 173	Miami Lakes	Florida
United States	Local Institution - 171	Miami Springs	Florida
United States	Local Institution - 154	Monroe	Louisiana
United States	Local Institution - 104	New York	New York
United States	Local Institution - 157	New York	New York
United States	Local Institution - 160	New York	New York
United States	Local Institution - 181	Oceanside	California
United States	Local Institution - 174	Omaha	Nebraska
United States	NRC Research Institute	Orange	California
United States	Local Institution - 124	Orange City	Florida
United States	Local Institution - 139	Overland Park	Kansas
United States	Local Institution - 156	Pembroke Pines	Florida
United States	Local Institution - 161	Phoenix	Arizona
United States	CNRI - Los Angeles, LLC	Pico Rivera	California
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	At Health Texas	Richmond	Texas
United States	CITrials, Inc. - Riverside & San Bernardino County	Riverside	California
United States	Psychiatry and Alzheimer's Care of Rochester. PLLC	Rochester	New York
United States	Green Mountain Research Institute	Rutland	Vermont
United States	Local Institution - 178	Saint Louis	Missouri
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	Local Institution - 164	Stanford	California
United States	Richmond Behavioral Associates ERG Clinical Research - New York PLLC	Staten Island	New York
United States	Interventional Psychiatry of Tampa Bay	Tampa	Florida
United States	CenExel Collaborative Neuroscience Research	Torrance	California
United States	Local Institution - 185	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Karuna Therapeutics

Countries where clinical trial is conducted

United States,  Bulgaria,  India,  Poland,  Romania,  Serbia,  United Kingdom, 

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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting