A Study to Assess Safety and Efficacy of KarXT in Adult Patients With Schizophrenia

NCT03697252 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KAR-004
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 12

Brief Summary

This is a Phase 2, randomized, double-blinded, placebo-controlled, inpatient study to examine the efficacy, safety, and tolerability profile of KarXT in adult subjects diagnosed with DSM-5 schizophrenia who are in an acute exacerbation phase. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline and trospium chloride) (xanomeline 125 mg/trospium 30 mg twice daily \[BID\]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a Diagnostic and Statistical Manual-Fifth Edition (DSM-5) diagnosis of schizophrenia. The secondary objectives of the study are to assess overall safety and tolerability of KarXT in adult inpatients with a DSM-5 diagnosis of schizophrenia.

Conditions

Schizophrenia

Keywords

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5

  The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants were rated from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

  Baseline and Week 5

Secondary Outcomes (5)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5

  Baseline and Week 5

• Number of Participants With Each Clinical Global Impression - Severity (CGI-S) Score at Baseline and 5 Weeks

  Baseline and Week 5

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5

  Baseline and Week 5

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Score

  Baseline and Week 5

• Percentage of Participants Who Were Clinical Global Impression - Severity of Illness (CGI-S) Responders

  Week 5

Study Arms (2)

KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Placebo

PLACEBO COMPARATOR

Drug: Placebo Capsules

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

Xanomeline 50 mg/trospium 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium 20 mg BID on days 3-7. The dose is increased to xanomeline 125 mg/trospium 30 mg BID on days 8-34 unless the subject is experiencing adverse events from the xanomeline 100 mg/trospium 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium 30 mg will have the option to return to xanomeline 100 mg/trospium 20 mg depending on clinical response and tolerability. Dosing must not change after Visit 7 of the study (at 21 ± 2 days of dosing) and may be decreased for tolerability reasons no more than once during the study.

Also known as: KarXT

KarXT

Placebo Capsules DRUG

Placebo Capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is aged 18-60 years, inclusive, at screening
• Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
• Subject is experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months before screening
• Positive and Negative Syndrome Scale total score between 80 and 120, inclusive, at screening
• Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items at screening:
• Item 1 (P1; delusions)
• Item 2 (P2; conceptual disorganization)
• Item 3 (P3; hallucinatory behavior)
• Item 6 (P6; suspiciousness/persecution)
• There should not be a change (improvement) in PANSS total score between screening and baseline of more than 20%
• Subjects taking a depot antipsychotic could not have received a dose of medication for at least 1 and a half injection cycles before baseline (eg, 3 or more weeks off for a 2-week cycle)
• Subject is capable of providing informed consent
• A signed ICF must be provided before any study assessments are performed
• Subject must be fluent (oral and written) in English in order to consent
• Subject must have CGI-S score of ≥ 4 at screening and baseline visits

You may not qualify if:

• Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening)
• History or presence of 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, would jeopardize the safety of the subject or the validity of the study results, to exclude patients with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on the liver function test results.
• History of or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
• History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
• Has a DSM-5 diagnosis of moderate to severe substance abuse disorder (except tobacco use disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 at screening), or current abuse as determined by urine toxicology screen or alcohol test. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before he/she can be allowed into the study.
• Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening
• Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not allowed for 90 days after the final dose of study drug
• If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect their ability to adhere to the protocol visit schedule or fulfill visit requirements
• Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening
• Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) or required clozapine within the last 12 months
• Risk of violent or destructive behavior
• Current involuntary hospitalization or incarceration
• Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months of screening

Sponsors & Collaborators

• Karuna Therapeutics: lead

Study Sites (12)

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

Synergy East

Lemon Grove, California, 91945, United States

Location

Collaborative Neuroscience Network, LLC.

Long Beach, California, 90806, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

CBH Health, LLC

Gaithersburg, Maryland, 20877, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Midwest Clinical Research Center (and IP Shipment)

Dayton, Ohio, 45417, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

InSite Clinical Research, LLC

DeSoto, Texas, 75115, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

Related Publications (7)

• Yeung PP, Breier A, Zhu H, Kaul I, Marcus RN. Xanomeline and Trospium Chloride for the Treatment of Agitation Associated With Schizophrenia: PANSS-Excited Component Results From 3 Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Mar 24;86(2):24m15668. doi: 10.4088/JCP.24m15668.

  PMID: 40215379 DERIVED

• Citrome L, Neugebauer NM, Meli AA, Kando J. Xanomeline and Trospium Chloride Versus Placebo for the Treatment of Schizophrenia: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. Neuropsychiatr Dis Treat. 2025 Apr 5;21:761-773. doi: 10.2147/NDT.S503494. eCollection 2025.

  PMID: 40212458 DERIVED

• Kaul I, Claxton A, Sawchak S, Sauder C, Brannan SK, Raj E, Ruan S, Konis G, Brown D, Cutler AJ, Marcus R. Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Feb 26;86(1):24m15497. doi: 10.4088/JCP.24m15497.

  PMID: 40047530 DERIVED

• Sauder C, Allen LA, Baker E, Miller AC, Paul SM, Brannan SK. Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study. Transl Psychiatry. 2022 Nov 21;12(1):491. doi: 10.1038/s41398-022-02254-9.

  PMID: 36414626 DERIVED

• Weiden PJ, Breier A, Kavanagh S, Miller AC, Brannan SK, Paul SM. Antipsychotic Efficacy of KarXT (Xanomeline-Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study. J Clin Psychiatry. 2022 May 11;83(3):21m14316. doi: 10.4088/JCP.21m14316.

  PMID: 35552528 DERIVED

• Targum SD, Murphy C, Breier A, Brannan SK. Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial. J Psychiatr Res. 2021 Dec;144:241-246. doi: 10.1016/j.jpsychires.2021.10.027. Epub 2021 Oct 21.

  PMID: 34700212 DERIVED

• Brannan SK, Sawchak S, Miller AC, Lieberman JA, Paul SM, Breier A. Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia. N Engl J Med. 2021 Feb 25;384(8):717-726. doi: 10.1056/NEJMoa2017015.

  PMID: 33626254 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Stephen Brannan
• Organization: Karuna Therapeutics, Inc.

sbrannan@karunatx.com

857-449-2234

Study Officials

• Stephen Brannan, MD

  Karuna Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 5, 2018
• Study Start: September 18, 2018
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: October 26, 2020
• Results First Posted: September 28, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)