An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia

NCT05643170 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: KAR-014
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 3b, 3-year, open-label, multi-center study in which patients with DSM-5 diagnosis of schizophrenia whose current medication(s) is not well tolerated and/or clinical symptoms are not well controlled will be switched to receive KarXT. The primary objectives of the study are to assess the long-term safety and tolerability of KarXT and assess effectiveness, persistence, and durability of effect of KarXT through the Investigator Assessment Questionnaire (IAQ) and Clinical Global Impression - Severity of Illness (CGI-S) scale in patients with a diagnosis of schizophrenia. The secondary objectives are to further assess the effectiveness using the Clinical Global Impression, Global Improvement (CGI-I), long-term safety and tolerability of KarXT, and evaluation of scores from multiple additional patient scales and assessments throughout the study.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (3)

• The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation

  An Adverse Event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening, worsens during the study, regardless of the suspected cause of the event.

  From first dose to 28 days post last dose (up to approximately 113 days)

• Investigator Assessment Questionnaire (IAQ) Scores

  The Investigator's Assessment Questionnaire (IAQ) evaluates all health concerns associated with antipsychotic use in patients with schizophrenia or schizoaffective disorder. The IAQ total score is defined as the sum of 10 items (positive symptoms, negative symptoms, somnolence, weight gain, signs and symptoms of prolactin elevation, akathisia, EPS, cognition, energy, and mood) for a total max score of 50; each item is rated on a 5-point Likert scale (1 = Much better, 2 = Slightly better, 3 = About the same, 4 = Slightly worse, and 5 = Much worse) where higher score indicate increased health concerns.

  At visit 1, 3, 5 (Baseline, week 4, 8), and early termination visit (study day 85)

• Clinical Global Impression - Severity of Illness (CGI-S) Scores

  The Clinical Global Impression - Severity (CGI-S) is a rating scale completed independently by a clinician that is used to measure illness and symptom severity in subjects with mental disorders. It is used to rate the severity of a subject's illness at the time of assessment. The modified CGI-S asks the clinician 1 question: "Considering your total clinical experience, how mentally ill is the subject at this time?" The clinician's answer is 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 subjects.

  At visit 1, 2, 3, 5 (baseline, week 2, 4, 8)

Secondary Outcomes (4)

• The Number of Participants With Serious Treatment-Emergent Adverse Events (TESAEs)

  From first dose to 28 days post last dose (up to approximately 113 days)

• The Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESI)

  From first dose to 28 days post last dose (up to approximately 113 days)

• Clinical Global Impression - Improvement (CGI-I) Score

  At visit 2, 3, 5 (Weeks 2, 4, 8)

• Medication Satisfaction Questionnaire (MSQ) Score

  Visit 5 (Week 8)

Study Arms (1)

KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

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

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:

• Patient is aged 18 to 65 years, inclusive, at screening.
• Patient can provide informed consent.
• A signed informed consent form (ICF) must be provided before any study assessments are performed.
• Patient must be fluent (oral and written) in the language of the ICF to consent.
• Patient has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM 5 (American Psychiatric Association, 2013) criteria and has been in the continuous care of the clinician or practice for at least 6 months prior to entering the study.
• The patient is dissatisfied with the side effects or general tolerability of their current antipsychotic medication, and for this reason, desires to change medications. Or, the patient is dissatisfied with the overall effectiveness or benefit of their current antipsychotic medication, and for this reason, desires to change medications.
• The patient has not required psychiatric hospitalization, acute crisis intervention, or other increase in their level of care due to symptom exacerbation within 4 weeks of screening, and in the opinion of the investigator, is psychiatrically stable to be managed in an outpatient setting.
• The patient has a CGI-S score of ≤4 (moderately severe or less) at screening and baseline visits.
• For at least 30 days prior to screening, the patient must have been prescribed and have taken an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.
• Patient has an identified, reliable caregiver/informant that is willing (by informed consent) and able to respond to the ZBI 22 caregiver burden scale at specified visits. If the patient has been the patient of the investigator for ≥6 months and, in the opinion of the investigator, the patient is self-sufficient, then a caregiver/informant may not be necessary.
• Patient resides in a stable living situation and is anticipated to remain in a stable living situation for the duration of the study, in the opinion of the investigator.
• If a woman of childbearing potential (WOCBP) or a man whose sexual partner(s) is a WOCBP, the patient must be willing and able to adhere to the contraception guidelines as defined in Section 12.1 Appendix 1.

You may not qualify if:

• The patient has a history of or presence of a 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, is likely to jeopardize the safety of the patient or the validity of the study results.
• Patient has a history of or is at high risk of urinary retention, gastric retention, or narrow angle glaucoma.
• Patient has a history of irritable bowel syndrome (with or without constipation) or constipation requiring treatment for more than 30 days within the last 6 months.
• Clinically significant abnormal finding on the physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
• Patient is pregnant, lactating, or less than 3 months postpartum.
• Patient has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening and/or baseline or patients who have prolonged symptoms of past infection, long COVID, that, in the opinion of the investigator, may interfere with the interpretation of safety during the study.
• Patient with extreme concerns relating to global pandemics, such as COVID-19, that precludes study participation.
• Patient is currently or recently (within 4 weeks of screening) involuntary hospitalization or incarceration.
• Patient participated in another clinical study in which they received an experimental or investigational drug agent within 30 days prior to screening.

Sponsors & Collaborators

• Karuna Therapeutics: lead

Study Sites (5)

Advanced Discovery Research, LLC

Atlanta, Georgia, 30318, United States

Location

Seven Counties Services, Inc.

Louisville, Kentucky, 40203, United States

Location

Mid Ohio Behavioral Health

Columbus, Ohio, 43205, United States

Location

OnSite Clinical Solutions, LLC

Rock Hill, South Carolina, 29732, United States

Location

Integrated Clinical Research

St. George, Utah, 84770, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: November 22, 2022
• First Posted: December 8, 2022
• Study Start: November 8, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 8, 2023
• Last Updated: June 12, 2024
• Results First Posted: June 12, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)