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NCT04659161

A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)

Completed Phase 3 Results posted Last updated 12 December 2023
What this trial tests

Phase 3 trial testing Xanomeline and Trospium Chloride Capsules in Schizophrenia in 252 participants. Completed in 24 May 2022.

Timeline
16 December 2020
Primary endpoint
24 May 2022
24 May 2022

Quick facts

Lead sponsorKaruna Therapeutics, Inc., a Bristol Myers Squibb company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment252
Start date16 December 2020
Primary completion24 May 2022
Estimated completion24 May 2022
Sites22 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Karuna Therapeutics, Inc., a Bristol Myers Squibb company — full company profile →

Who can join

Adults 18 to 65, any sex, with Schizophrenia or Schizophrenia; Psychosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5 Primary · Baseline and 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 are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. 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.

GroupValue95% CI
KarXT-21.2± 1.652
Placebo-11.6± 1.600
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5 Secondary · Baseline and 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 are rated from 1 to 7 on each symptom scale. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

GroupValue95% CI
KarXT-6.8± 0.526
Placebo-3.9± 0.512
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5 Secondary · Baseline and Week 5

The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

GroupValue95% CI
KarXT-3.4± 0.479
Placebo-1.6± 0.466
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score Secondary · Baseline and Week 5

The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

GroupValue95% CI
KarXT-4.2± 0.530
Placebo-2.0± 0.517
Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5 Secondary · Baseline and Week 5

The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer 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 participants.

GroupValue95% CI
KarXT-1.2± 0.103
Placebo-0.7± 0.099
Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5 Secondary · Baseline and 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 are 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 PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.

GroupValue95% CI
KarXT51
Placebo28

Adverse events — posted to ClinicalTrials.gov

Time frame: From the start of study drug administration up to Week 5.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

KarXT
Serious: 2/126 (2%)
Deaths: 0/126
Placebo
Serious: 2/125 (2%)
Deaths: 0/125

Serious adverse events (3 terms)

ReactionSystemKarXTPlacebo
Suicidal ideationPsychiatric disorders
AppendicitisInfections and infestations
SchizophreniaPsychiatric disorders
Other adverse events (25 terms — click to expand)

ReactionSystemKarXTPlacebo
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
HypertensionVascular disorders
DizzinessNervous system disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
AgitationPsychiatric disorders
Abdominal discomfortGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
SomnolenceNervous system disorders
AnxietyPsychiatric disorders
InsomniaPsychiatric disorders
Psychotic disorderPsychiatric disorders
Vision blurredEye disorders
ToothacheGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Heart rate increasedInvestigations
Orthostatic hypotensionVascular disorders
Back painMusculoskeletal and connective tissue disorders
Salivary hypersecretionGastrointestinal disorders
TachycardiaCardiac disorders

Most-reported serious reactions: Suicidal ideation, Appendicitis, Schizophrenia.

Data from ClinicalTrials.gov NCT04659161 adverse events section.

Sponsor's own description

This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in adult subjects who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily \[BID\]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in disease severity and symptoms, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.
    Kaul I, Sawchak S, Correll CU, Kakar R, et al · · 2024 · cited 144× · PMID 38104575 · DOI 10.1016/s0140-6736(23)02190-6
  2. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial.
    Kaul I, Sawchak S, Walling DP, Tamminga CA, et al · · 2024 · cited 110× · PMID 38691387 · DOI 10.1001/jamapsychiatry.2024.0785
  3. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
    Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
  4. Safety and tolerability of KarXT (xanomeline-trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia.
    Correll CU, Angelov AS, Miller AC, Weiden PJ, et al · · 2022 · cited 47× · PMID 36463237 · DOI 10.1038/s41537-022-00320-1
  5. Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.
    Johnson CR, Kangas BD, Jutkiewicz EM, Bergman J, et al · · 2022 · cited 34× · PMID 35203607 · DOI 10.3390/biomedicines10020398
  6. Understanding translational research in schizophrenia: A novel insight into animal models.
    Malik JA, Yaseen Z, Thotapalli L, Ahmed S, et al · · 2023 · cited 18× · PMID 36692676 · DOI 10.1007/s11033-023-08241-7
  7. Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.
    Veselinović T, Neuner I. · · 2022 · cited 18× · PMID 35831706 · DOI 10.1007/s40263-022-00935-z
  8. Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials.
    Kaul I, Sawchak S, Claxton A, Sauder C, et al · · 2024 · cited 16× · PMID 39488504 · DOI 10.1038/s41537-024-00525-6

Verify or expand the search:

Other trials of Xanomeline and Trospium Chloride Capsules

Trials testing the same drug.

Other recruiting trials for Schizophrenia

Currently open trials in the same condition.

Other Karuna Therapeutics, Inc., a Bristol Myers Squibb company trials

Trials by the same sponsor.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing