Clinical trial NCT05304767: An Extension Study to Assess Long-Term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. Subject is aged ≥18 to \<66 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: From initial dose to safety follow-up visit (54 weeks) or early termination
Secondary outcomes:
measure: Incidence of serious treatment-emergent adverse events (TEAEs)
timeFrame: From initial dose to safety follow-up visit (54 weeks) or early termination
measure: Incidence of TEAEs leading to discontinuation of study drug
timeFrame: From initial dose to safety follow-up visit (54 weeks) or early termination
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Alea Research
state: Arizona
city: Little Rock
country: United States
facility: Pillar Clinical Research LLC
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center, Inc.
state: California
city: Bellflower
country: United States
facility: CITrials - Bellflower
state: California
city: Cerritos
country: United States
facility: Synexus Clinical Research US, Inc.
state: California
city: Culver City
country: United States
facility: Proscience Research Group
state: California
city: Garden Grove
country: United States
facility: CenExel Collaborative Neuroscience Research
state: California
city: La Habra
country: United States
facility: Local Institution - 152
state: California
city: Lafayette
country: United States
facility: Sunwise Clinical Research, LLC.
state: California
city: Lemon Grove
country: United States
facility: Synergy Clinical Research of Escondido
state: California
city: Los Angeles
country: United States
facility: Local Institution - 141
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles, LLC
state: California
city: Riverside
country: United States
facility: CITrials, Inc. - Riverside & San Bernardino County
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Torrance
country: United States
facility: CenExel Collaborative Neuroscience Research
state: California
city: Coral Gables
country: United States
facility: Prestige Clinical Research Center, Inc.
state: Florida
city: Hialeah
country: United States
facility: Reliable Clinical Research LLC
state: Florida
city: Hialeah
country: United States
facility: Galiz Research, LLC
state: Florida
city: Lauderhill
country: United States
facility: Local Institution - 105
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Local Institution - 120
state: Florida
city: Miami Lakes
country: United States
facility: Assertive Research Center
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I-IV, Inc.
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute, Inc.
state: Florida
city: Orange City
country: United States
facility: Local Institution - 124
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center, Inc.
state: Florida
city: Tampa
country: United States
facility: Interventional Psychiatry of Tampa Bay
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Synexus Clinical Research US, Inc.
state: Georgia
city: Atlanta
country: United States
facility: CenExel Atlanta Center for Medical Research
state: Georgia
city: Augusta
country: United States
facility: Local Institution - 135
state: Georgia
city: Decatur
country: United States
facility: CenExel iResearch Atlanta
state: Georgia
city: Marietta
country: United States
facility: Psych Atlanta, P.C.
state: Georgia
city: Savannah
country: United States
facility: Local Institution - 191
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 177
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 142
state: Illinois
city: Chicago
country: United States
facility: Uptown Research Institute, LLC
state: Illinois
city: Overland Park
country: United States
facility: Local Institution - 139
state: Kansas
city: Monroe
country: United States
facility: Local Institution - 154
state: Louisiana
city: Gaithersburg
country: United States
facility: CenExel Center for Behavioral Health
state: Maryland
city: Boston
country: United States
facility: Local Institution - 158
state: Massachusetts
city: Boston
country: United States
facility: Boston University - PARENT
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 269
state: Massachusetts
city: Worcester
country: United States
facility: Local Institution - 185
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 184
state: Michigan
city: Grand Rapids
country: United States
facility: Local Institution - 149
state: Michigan
city: Kalamazoo
country: United States
facility: Local Institution - 162
state: Michigan
city: Saint Louis
country: United States
facility: Local Institution - 129
state: Missouri
city: Saint Louis
country: United States
facility: Arch Clinical Trials LLC
state: Missouri
city: Omaha
country: United States
facility: Omaha Insomnia and Psychiatric Services LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Altea Research Institute, Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: Local Institution - 147
state: Nevada
city: Berlin
country: United States
facility: CenExel HRI Marlton
state: New Jersey
city: New York
country: United States
facility: Local Institution - 104
state: New York
city: New York
country: United States
facility: Manhattan Psychiatric Center
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine, PLLC
state: New York
city: Rochester
country: United States
facility: Psychiatry and Alzheimer's Care of Rochester. PLLC
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates ERG Clinical Research - New York PLLC
state: New York
city: Hickory
country: United States
facility: IMA Clinical Research Hickory
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 165
state: Ohio
city: Garfield Heights
country: United States
facility: Local Institution - 168
state: Ohio
city: Independence
country: United States
facility: Insight Clinical Trials LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution - 194
state: Oklahoma
city: Eugene
country: United States
facility: Prevention Science Institute
state: Oregon
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: DeSoto
country: United States
facility: Local Institution - 189
state: Texas
city: Fort Worth
country: United States
facility: JPS Health Network
state: Texas
city: Houston
country: United States
facility: Local Institution - 183
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network LLC
state: Texas
city: Irving
country: United States
facility: University Hills Clinical Research - Irving
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Richmond
country: United States
facility: At Health Texas
state: Texas
city: Rutland
country: United States
facility: Green Mountain Research Institute
state: Vermont
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Sofia
country: Bulgaria
facility: Center for Mental Health Center - Sofia District EOOD
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: Medical Center Akademika EOOD
state: Sofia-Grad
city: Kazanlak
country: Bulgaria
facility: MHAT Dr. Hristo Stambolski, EOOD
state: Stara Zagora
city: Cherven Bryag
country: Bulgaria
facility: Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry - Dr Ivo Natsov
city: Dupnitsa
country: Bulgaria
facility: Medical Centre 'Asklepii', OOD
city: Kardzhali
country: Bulgaria
facility: Medical Center Lifemed
city: Novi Iskar
country: Bulgaria
facility: State Psychiatric Hospital 'Sv. Ivan Rilski', Novi Iskar
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven OOD
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Plovdiv
country: Bulgaria
facility: UMHAT Sv. Georgi, EAD
city: Plovdiv
country: Bulgaria
facility: Local Institution - 321
city: Razgrad
country: Bulgaria
facility: MHAT Sveti Ivan Rilski - Razgrad AD
city: Sliven
country: Bulgaria
facility: MHAT Dr Ivan Seliminski AD
city: Sofia
country: Bulgaria
facility: Medical Center 'Sv.Naum'
city: Sofia
country: Bulgaria
facility: DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
city: Sofia
country: Bulgaria
facility: Local Institution - 320
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica, OOD
city: Targovishte
country: Bulgaria
facility: Medical Center VAS OOD
city: Varna
country: Bulgaria
facility: DCC Mladost M - Varna, OOD
city: Vratsa
country: Bulgaria
facility: Mental Health Center-Vratsa EOOD
city: Klecany
country: Czechia
facility: Local Institution - 905
city: Ostrava - Poruba
country: Czechia
facility: Local Institution - 903
city: Plzen
country: Czechia
facility: Local Institution - 904
city: Praha 10
country: Czechia
facility: Local Institution - 906
city: Praha 1
country: Czechia
facility: Local Institution - 901
city: Praha 8
country: Czechia
facility: Local Institution - 902
city: Guwahati
country: India
facility: Local Institution - 616
state: Assam
city: Ahmedabad
country: India
facility: Local Institution - 607
state: Gujarat
city: Ahmedabad
country: India
facility: Local Institution - 604
state: Gujarat
city: Surat
country: India
facility: Local Institution - 609
state: Gujarat
city: Vadodara
country: India
facility: Local Institution - 613
state: Gujarat
city: Belgavi
country: India
facility: Local Institution - 617
state: Karnataka
city: Mangalore
country: India
facility: Local Institution - 614
state: Karnataka
city: Mangalore
country: India
facility: Local Institution - 602
state: Karnataka
city: Mysore
country: India
facility: Local Institution - 601
state: Karnataka
city: Kozhikode
country: India
facility: Local Institution - 611
state: Kerala
city: Aurangabad
country: India
facility: Local Institution - 610
state: Maharashtra
city: Nagpur
country: India
facility: Local Institution - 603
state: Maharashtra
city: Nashik
country: India
facility: Local Institution - 608
state: Maharashtra
city: Nashik
country: India
facility: Local Institution - 605
state: Maharashtra
city: Ajmer
country: India
facility: Local Institution - 615
state: Rajasthan
city: Rajkot
country: India
facility: Local Institution - 606
state: Rajasthan
city: Lucknow
country: India
facility: Local Institution - 612
state: Uttar Pradesh
city: Konan-shi
country: Japan
facility: Local Institution - 258
state: Aichi-Ken
city: Toyoake-shi
country: Japan
facility: Local Institution - 250
state: Aichi-Ken
city: Fukuoka-shi
country: Japan
facility: Local Institution - 255
state: Fukuoka-Ken
city: Shirakawa-shi
country: Japan
facility: Local Institution - 257
state: Fukushima-Ken
city: Karatsu-shi
country: Japan
facility: Local Institution - 254
state: Saga-Ken
city: Shinjuku-ku
country: Japan
facility: Local Institution - 256
state: Tokyo-To
city: Meguro-ku
country: Japan
facility: Local Institution - 253
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Sangenjaya Neurology- Psychosomatic Clinic
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Local Institution - 910
state: Tokyo
city: Bialystok
country: Poland
facility: Local Institution - 506
city: Gdansk
country: Poland
facility: Local Institution - 507
city: Grudziadz
country: Poland
facility: Local Institution - 509
city: Katowice
country: Poland
facility: Local Institution - 502
city: Kielce
country: Poland
facility: Local Institution - 501
city: Lodz
country: Poland
facility: Local Institution - 503
city: Lublin
country: Poland
facility: Local Institution - 505
city: Suchy Las
country: Poland
facility: Local Institution - 508
city: Tuszyn
country: Poland
facility: Local Institution - 504
city: Brasov
country: Romania
facility: Local Institution - 803
city: Bucuresti
country: Romania
facility: Local Institution - 804
city: Bucuresti
country: Romania
facility: Local Institution - 810
city: Bucuresti
country: Romania
facility: Local Institution - 809
city: Bucuresti
country: Romania
facility: Local Institution - 802
city: Bucuresti
country: Romania
facility: Local Institution - 807
city: Craiova
country: Romania
facility: Local Institution - 808
city: Galati
country: Romania
facility: Local Institution - 801
city: Iasi
country: Romania
facility: Local Institution - 806
city: Sibiu
country: Romania
facility: Local Institution - 805
city: Belgrade
country: Serbia
facility: Clinical Center ' Dr Dragisa Misovic Dedinje'
city: Belgrade
country: Serbia
facility: Local Institution - 413
city: Belgrade
country: Serbia
facility: Local Institution - 417
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Beograd
country: Serbia
facility: Institute of Mental Health
city: Gornja Toponica
country: Serbia
facility: Special Hospital for Psychiatric Diseases 'Gornja Toponica'
city: Kovin
country: Serbia
facility: Special Hospital for Psychiatric Diseases 'Kovin'
city: Kovin
country: Serbia
facility: Local Institution - 404
city: Kragujevac
country: Serbia
facility: Local Institution - 408
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Nis
country: Serbia
facility: Local Institution - 415
city: Novi Knezevac
country: Serbia
facility: Local Institution - 416
city: Novi Knezevac
country: Serbia
facility: Special Hospital for Psychiatric Diseases 'Sveti Vracevi'
city: Vrsac
country: Serbia
facility: Local Institution - 409
city: Bodmin
country: United Kingdom
facility: Local Institution - 707
state: Cornwall
city: Brighton
country: United Kingdom
facility: Local Institution - 705
state: East Sussex
city: London
country: United Kingdom
facility: Local Institution - 701
state: Greater London
city: Ashton Under Lyne
country: United Kingdom
facility: Local Institution - 706
state: Lancashire
city: Oxford
country: United Kingdom
facility: Local Institution - 708
state: Oxfordshire
city: Chertsey
country: United Kingdom
facility: Local Institution - 702
state: Surrey
city: Birmingham
country: United Kingdom
facility: Local Institution - 703
state: West Midlands
city: Glasgow
country: United Kingdom
facility: Local Institution - 704
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: