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

NCT05304767 | Completed Phase 3 FDA Drug

• 2 other identifiers: CN012-0009KAR-013
• Study Type: interventional
• Target: 290
• Locations: 4 countries
• Sites: 94

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs)

  From initial dose to safety follow-up visit (54 weeks) or early termination

Secondary Outcomes (2)

• Incidence of serious treatment-emergent adverse events (TEAEs)

  From initial dose to safety follow-up visit (54 weeks) or early termination

• Incidence of TEAEs leading to discontinuation of study drug

  From initial dose to safety follow-up visit (54 weeks) or early termination

Study Arms (1)

Drug: KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

KarXT 50 mg/20 mg BID KarXT 75mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID

Drug: KarXT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is aged ≥18 to \<66 years at the time of randomization of Study KAR-012
• Subject has successfully completed the treatment period of Study KAR-012
• Subject has been compliant with the procedures in Study KAR-012 (in the Investigator's judgement)
• 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.
• Subject is capable of providing signed Informed Consent Form before any study assessments will be performed
• Subject resides in a stable living situation, in the opinion of the Investigator
• 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.
• 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).

You may not qualify if:

• 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:
• 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
• 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
• Female subject is pregnant
• 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
• Risk of violent or destructive behavior as per Investigator's judgement
• Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study
• History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator
• Subject is taking, or plans to take while in the study, any prohibited concomitant medication
• For all male subjects only, any one of the following:
• History of bladder stones
• History of recurrent urinary tract infections
• Serum prostate specific antigen (PSA) \>10 ng/mL
• An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6
• 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.

Sponsors & Collaborators

• Karuna Therapeutics, Inc., a Bristol Myers Squibb company: lead

Study Sites (94)

Local Institution - 161

Phoenix, Arizona, 85012, United States

Location

Local Institution - 175

Little Rock, Arkansas, 72204, United States

Location

Local Institution - 112

Little Rock, Arkansas, 72211, United States

Location

Local Institution - 146

Anaheim, California, 92805, United States

Location

Local Institution - 130

Bellflower, California, 90706, United States

Location

Local Institution - 110

Cerritos, California, 90703, United States

Location

Local Institution - 167

Culver City, California, 90230, United States

Location

Local Institution - 127

Garden Grove, California, 92845, United States

Location

Local Institution - 152

La Habra, California, 90631-3842, United States

Location

Local Institution - 126

Lafayette, California, 94549, United States

Location

Local Institution - 131

Lemon Grove, California, 91945-2956, United States

Location

Local Institution - 181

Oceanside, California, 92056, United States

Location

Local Institution - 150

Orange, California, 92868, United States

Location

Local Institution - 170

Pico Rivera, California, 90660, United States

Location

Local Institution - 144

Riverside, California, 92506, United States

Location

Local Institution - 164

Stanford, California, 94305, United States

Location

Local Institution - 109

Torrance, California, 90504, United States

Location

Local Institution - 186

Coral Gables, Florida, 33134, United States

Location

Local Institution - 182

Hialeah, Florida, 33012, United States

Location

Local Institution - 133

Hialeah, Florida, 33016-1814, United States

Location

Local Institution - 105

Lauderhill, Florida, 33319-4985, United States

Location

Local Institution - 145

Miami, Florida, 33122-1335, United States

Location

Local Institution - 171

Miami, Florida, 33166, United States

Location

Local Institution - 173

Miami Lakes, Florida, 33014, United States

Location

Local Institution - 153

Miami Lakes, Florida, 33016, United States

Location

Local Institution - 156

Pembroke Pines, Florida, 33025, United States

Location

Local Institution - 155

Tampa, Florida, 33629, United States

Location

Local Institution - 136

Atlanta, Georgia, 30303-3031, United States

Location

Local Institution - 111

Atlanta, Georgia, 30328, United States

Location

Local Institution - 192

Atlanta, Georgia, 30331, United States

Location

Local Institution - 138

Decatur, Georgia, 30030, United States

Location

Local Institution - 169

Marietta, Georgia, 30060, United States

Location

Local Institution - 151

Chicago, Illinois, 60640, United States

Location

Local Institution - 166

Gaithersburg, Maryland, 20877, United States

Location

Local Institution - 187

Boston, Massachusetts, 02118, United States

Location

Local Institution - 129

St Louis, Missouri, 63128, United States

Location

Local Institution - 178

St Louis, Missouri, 63141, United States

Location

Local Institution - 174

Omaha, Nebraska, 68144, United States

Location

Local Institution - 148

Las Vegas, Nevada, 89102, United States

Location

Local Institution - 188

Berlin, New Jersey, 08009, United States

Location

Local Institution - 104

New York, New York, 10017, United States

Location

Local Institution - 160

New York, New York, 10035, United States

Location

Local Institution - 157

New York, New York, 10036, United States

Location

Local Institution - 108

Rochester, New York, 14623, United States

Location

Local Institution - 113

Staten Island, New York, 10314-1607, United States

Location

Local Institution - 176

Hickory, North Carolina, 28601, United States

Location

Local Institution - 163

Independence, Ohio, 44131, United States

Location

Local Institution - 179

Eugene, Oregon, 97403, United States

Location

Local Institution - 128

Austin, Texas, 78754, United States

Location

Local Institution - 190

Fort Worth, Texas, 76104, United States

Location

Local Institution - 180

Houston, Texas, 77074, United States

Location

Local Institution - 103

Irving, Texas, 75062-2757, United States

Location

Local Institution - 172

Richardson, Texas, 75080, United States

Location

Local Institution - 159

Richmond, Texas, 77407, United States

Location

Local Institution - 140

Rutland, Vermont, 05701, United States

Location

Local Institution - 101

Bellevue, Washington, 98007, United States

Location

Local Institution - 306

Sofia, Sofia-Grad, 1202, Bulgaria

Location

Local Institution - 309

Sofia, Sofia-Grad, 1463, Bulgaria

Location

Local Institution - 302

Kazanlak, Stara Zagora, 6100, Bulgaria

Location

Local Institution - 318

Cherven Bryag, 5980, Bulgaria

Location

Local Institution - 311

Dupnitsa, 2600, Bulgaria

Location

Local Institution - 316

Kardzhali, 6600, Bulgaria

Location

Local Institution - 304

Novi Iskar, 1282, Bulgaria

Location

Local Institution - 301

Pleven, 5800, Bulgaria

Location

Local Institution - 315

Pleven, 5800, Bulgaria

Location

Local Institution - 314

Plovdiv, 4002, Bulgaria

Location

Local Institution - 321

Plovdiv, 4004, Bulgaria

Location

Local Institution - 313

Razgrad, 7200, Bulgaria

Location

Local Institution - 312

Sliven, 8800, Bulgaria

Location

Local Institution - 305

Sofia, 1113, Bulgaria

Location

Local Institution - 319

Sofia, 1408, Bulgaria

Location

Local Institution - 307

Sofia, 1510, Bulgaria

Location

Local Institution - 303

Sofia, 1680, Bulgaria

Location

Local Institution - 317

Targovishte, 7700, Bulgaria

Location

Local Institution - 308

Varna, 9020, Bulgaria

Location

Local Institution - 310

Vratsa, 3000, Bulgaria

Location

Local Institution - 250

Toyoake-shi, Aichi-ken, 470-1168, Japan

Location

Local Institution - 255

Fukuoka, Fukuoka, 819-0037, Japan

Location

Local Institution - 257

Shirakawa-shi, Fukushima, 961-0021, Japan

Location

Local Institution - 254

Karatsu-shi, Saga-ken, 847-0031, Japan

Location

Local Institution - 253

Meguro-ku, Tokyo, 1540012, Japan

Location

Sangenjaya Neurology- Psychosomatic Clinic

Setagaya-ku, Tokyo, 1540004, Japan

Location

Local Institution - 256

Shinjuku-ku, Tokyo-To, 162-0843, Japan

Location

Local Institution - 403

Belgrade, 101421, Serbia

Location

Local Institution - 402

Belgrade, 11000, Serbia

Location

Local Institution - 405

Belgrade, 11000, Serbia

Location

Local Institution - 411

Gornja Toponica, 705631, Serbia

Location

Local Institution - 414

Kovin, 26220, Serbia

Location

Local Institution - 404

Kovin, 306041, Serbia

Location

Local Institution - 401

Kragujevac, 34 000, Serbia

Location

Local Institution - 406

Kragujevac, 34 000, Serbia

Location

Local Institution - 407

Kragujevac, 34 000, Serbia

Location

Local Institution - 408

Kragujevac, 34 000, Serbia

Location

Local Institution - 410

Novi Kneževac, 23330, Serbia

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: March 31, 2022
• Study Start: March 7, 2022
• Primary Completion: March 25, 2026
• Study Completion: March 25, 2026
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

JP (7); US (56); SE (11); BU (20)