Trial Outcomes & Findings for An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-5) (NCT NCT04820309)

NCT ID: NCT04820309

Last Updated: 2025-09-17

Results Overview

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

566 participants

Primary outcome timeframe

From time of consent to end of study (approximately 400 days)

Results posted on

2025-09-17

Participant Flow

Participant milestones

Participant milestones
Measure
KarXT
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Overall Study
STARTED
566
Overall Study
COMPLETED
277
Overall Study
NOT COMPLETED
289

Reasons for withdrawal

Reasons for withdrawal
Measure
KarXT
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Overall Study
Adverse Event
96
Overall Study
ineligible for further treatment according to inclusion/exclusion criteria
1
Overall Study
Consent Withdrawn
93
Overall Study
failure to adhere to protocol
32
Overall Study
alcohol or drug use
6
Overall Study
Lost to Follow-up
46
Overall Study
Death
2
Overall Study
Pregnancy
1
Overall Study
Other reasons
12

Baseline Characteristics

An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-5)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Age, Continuous
47.4 Years
STANDARD_DEVIATION 11.76 • n=93 Participants
Sex: Female, Male
Female
191 Participants
n=93 Participants
Sex: Female, Male
Male
375 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
119 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
443 Participants
n=93 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
4 Participants
n=93 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=93 Participants
Race (NIH/OMB)
Asian
5 Participants
n=93 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants
n=93 Participants
Race (NIH/OMB)
Black or African American
389 Participants
n=93 Participants
Race (NIH/OMB)
White
164 Participants
n=93 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=93 Participants
Race (NIH/OMB)
Unknown or Not Reported
5 Participants
n=93 Participants

PRIMARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
466 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor, that results in death; is life-threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, and/or; is a congenital anomaly/birth defect using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Serious Treatment Emergent Adverse Events (STEAEs)
41 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With TEAE Leading to Study Drug Discontinuation
100 Participants

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 PANSS total scores.

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 positive symptoms in schizophrenia are the excess or distortion of normal function and the negative symptoms are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms.

Outcome measures

Outcome measures
Measure
KarXT
n=283 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in PANSS Total Score at Week 52
-5.5 Score on a Scale
Standard Deviation 11.11

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 PANSS positive scores.

PANSS positive score is the sum of all PANSS 7 positive symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility.

Outcome measures

Outcome measures
Measure
KarXT
n=283 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in PANSS Positive Score at Week 52
-1.9 Score on a Scale
Standard Deviation 3.71

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 PANSS negative scores.

PANSS negative score is the sum of all PANSS 7 negative symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The negative symptoms in schizophrenia are the diminution or loss of normal functions.

Outcome measures

Outcome measures
Measure
KarXT
n=283 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in PANSS Negative Score at Week 52
-0.8 Score on a Scale
Standard Deviation 4.42

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 PANSS marder factor negative scores.

PANSS Marder factor score is a subscale of the PANSS; the sum of 5 negative scales and 2 general scales (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). Participants are rated from 1 to 7 on each symptom subscale. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions.

Outcome measures

Outcome measures
Measure
KarXT
n=558 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in PANSS Marder Factor Negative Score at Week 52
-1.1 Score on a Scale
Standard Deviation 4.49

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 clinical global Impressions-severity (CGI-S) scores.

Completed independently by a clinician, the CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients, by asking the clinical 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness.

Outcome measures

Outcome measures
Measure
KarXT
n=283 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Clinical Global Impressions-severity (CGI-S) Score Week 52
-0.4 Score on a Scale
Standard Deviation 0.70

SECONDARY outcome

Timeframe: At baseline and week 52

Population: All treated participants with baseline and week 52 PANSS total scores.

A PANSS responder is defined as a participant with a reduction from baseline of at least a 30% improvement at Week 52 in the PANSS total score. 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. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms.

Outcome measures

Outcome measures
Measure
KarXT
n=283 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Percentage of Participants With a ≥30% Reduction in PANSS Total Score at Week 52
9.2 percentage of participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

LFT elevations, inclusive of drug-induced liver injury (DILI) and symptomatic orthostasis including syncope (a transient loss of consciousness or fainting) is to be captured as an AESI and reported as such. Non symptomatic orthostasis will not be reported as an AESI. Any such AESI due to any cause, whether or not related to KarXT, must be reported within 24 hours of occurrence or when the investigator becomes aware of the event.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Adverse Events of Special Interest (AESI)
19 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

The number of participants experiencing adverse events related to procholinergic symptoms (believed to be associated with xanomeline) and anticholinergic symptoms (believed to be associated with trospium) symptoms. Examples of procholinergic symptoms include vomiting, nausea, diarrhea, sweating and hyper-salivation. Examples of anticholinergic include dizziness, confusion, hallucinations, and somnolence.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Anticholinergic and Procholinergic Symptoms
Anticholinergic
159 Participants
Number of Participants With Anticholinergic and Procholinergic Symptoms
Procholinergic
210 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline SAS score.

The Simpson-Angus Rating Scale (SAS) is a clinical tool used to assess the severity of extrapyramidal symptoms (EPS), which are drug-induced movement disorders often associated with antipsychotic medications. The scale consists of 10 items, each rated from 0 (none) to 4 (severe), with a total score range of 0 to 40. Higher scores indicate more severe symptoms. The SAS helps clinicians monitor and manage EPS in patients, guiding treatment decisions to minimize these side effects.

Outcome measures

Outcome measures
Measure
KarXT
n=404 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Simpson-Angus Rating Scale (SAS)
0.1 Score on a Scale
Standard Deviation 0.48

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline BARS score.

The BARS for akathisia is a rating scale used to assess the severity of drug-induced akathisia, or restlessness, involuntary movements and inability to sit still. The range of scores is 0 to 14, with higher scores indicating greater severity.

Outcome measures

Outcome measures
Measure
KarXT
n=405 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Barnes Akathisia Rating Scale (BARS)
0.1 Score on a Scale
Standard Deviation 0.58

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline AIMS score.

The Abnormal Involuntary Movement Scale (AIMS) is a tool used to assess the severity of tardive dyskinesia and other involuntary movements, often caused by antipsychotic medications. It includes 12 items, with the first 10 focusing on specific body areas and movement severity, rated from 0 (none) to 4 (severe). The total score ranges from 0 to 28, with higher scores indicating more severe symptoms. AIMS helps clinicians monitor and manage these movement disorders, guiding treatment adjustments to reduce side effects.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS)
0.1 Score on a Scale
Standard Deviation 0.57

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline BMI results.

BMI is a person's weight in kilograms divided by the square of height in meters. Baseline is defined as measurements taken at screening.

Outcome measures

Outcome measures
Measure
KarXT
n=408 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Body Mass Index (BMI)
-0.761 kg/m^2
Standard Deviation 2.0108

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline waist circumference results.

The change in waist circumference in centimeters from baseline. Baseline is defined as measurements taken at screening.

Outcome measures

Outcome measures
Measure
KarXT
n=403 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Waist Circumference
-1.549 cm
Standard Deviation 7.3558

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline blood pressure results.

The change from baseline in orthostatic diastolic and systolic blood pressure measured while supine and standing after 2 minutes. Baseline is defined as measurements taken at screening.

Outcome measures

Outcome measures
Measure
KarXT
n=408 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Blood Pressure Values
Supine Systolic
0.1 mmHG
Standard Deviation 12.83
Change From Baseline in Blood Pressure Values
Standing Systolic
-0.7 mmHG
Standard Deviation 12.33
Change From Baseline in Blood Pressure Values
Supine Diastolic
0.1 mmHG
Standard Deviation 8.72
Change From Baseline in Blood Pressure Values
Standing Diastolic
-0.2 mmHG
Standard Deviation 8.26

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with baseline and at least one post-baseline heart rate results.

The change from baseline in orthostatic heart rate measured while supine and standing after 2 minutes. Baseline is defined as measurements taken at screening.

Outcome measures

Outcome measures
Measure
KarXT
n=408 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Change From Baseline in Heart Rate
Supine Heart Rate
0.7 beats/min
Standard Deviation 11.43
Change From Baseline in Heart Rate
Standing Heart Rate
0.1 beats/min
Standard Deviation 11.22

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

Laboratory assessments include: * Hematology * Serum chemistry * Urinalysis * HbA1c * Prolactin levels * Coagulation studies * Viral Serology * Pregnancy test

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
0 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

An electrocardiogram (ECG) measures electrical activity of the heart to detect cardiac problems.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram
0 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: Safety Population

A complete physical examination (body temperature, general appearance, head/eyes/ears/nose/throat \[HEENT\], examination of thorax and abdomen, assessment of cardiac, musculoskeletal, and circulatory systems, palpations for lymphadenopathy, and limited neurological examination) will be performed. A targeted physical examination includes at a minimum body temperature, a check of general appearance, as well as examination of organ systems that are relevant to the investigator based on review of the participant's reported AEs, review of systems, or concomitant medication use. These also include symptom-driven physical examinations which will be performed as clinically indicated at any study visit.

Outcome measures

Outcome measures
Measure
KarXT
n=566 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Clinically Significant Changes in Physical Examination
3 Participants

SECONDARY outcome

Timeframe: From time of consent to end of study (approximately 400 days)

Population: All treated participants with C-SSRS results.

The Columbia Suicide Severity Rating Scale (C-SSRS) is a tool used to assess the severity and immediacy of suicidal ideation and behavior. It covers suicidal thoughts, plans, and actions, including the frequency, intensity, and context of these behaviors. The C-SSRS does not use a numerical scoring system like some other assessment tools. Instead, it categorizes the severity of suicidal ideation and behavior based on specific criteria. The scale helps clinicians identify individuals at risk of suicide and monitor changes over time, guiding treatment decisions and ensuring safety. It is quick and easy to administer, making it useful in various clinical and research settings.

Outcome measures

Outcome measures
Measure
KarXT
n=406 Participants
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Wish to be dead
1 Participants
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Non-Specific Active Suicidal Thoughts
1 Participants
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Active Suicidal Ideation with any methods without intent to act
0 Participants
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Active Suicidal Ideation with some intent to act but without a plan
1 Participants
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Active Suicidal Ideation with specific plan and intent
0 Participants

Adverse Events

KarXT

Serious events: 41 serious events
Other events: 356 other events
Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure
KarXT
n=566 participants at risk
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Cardiac disorders
Angina pectoris
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Abdominal pain
0.35%
2/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Diarrhoea
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Dyspepsia
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Vomiting
0.35%
2/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
General disorders
Death
0.35%
2/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations
COVID-19
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations
Cellulitis
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations
Diverticulitis
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations
Localised infection
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations
Pneumonia
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Burns third degree
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Eye injury
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Fibula fracture
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Rib fracture
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Skin abrasion
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Skin laceration
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Injury, poisoning and procedural complications
Tibia fracture
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Dizziness
0.35%
2/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Dysarthria
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Paraesthesia
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Depression
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Depressive symptom
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Hallucination, auditory
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Panic attack
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Psychotic disorder
0.71%
4/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Schizophrenia
1.8%
10/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders
Suicide attempt
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Renal and urinary disorders
Acute kidney injury
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Renal and urinary disorders
Urinary retention
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders
Asthma
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders
Nasal turbinate hypertrophy
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Surgical and medical procedures
Psychosocial support
0.18%
1/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Other adverse events

Other adverse events
Measure
KarXT
n=566 participants at risk
All subjects started on a lead-in dose of KarXT 50/20 (50 mg xanomeline/20 mg trospium chloride) BID for the first 2 days (Days 1 and 2), followed by KarXT 100/20 BID for the remainder of Week 1 (Days 3 to 7). Dosing was titrated upwards on Day 8 to KarXT 125/30 BID unless the subject was continuing to experience AEs from the previous dose (KarXT 100/20 BID). All subjects who had their dose increased to KarXT 125/30 BID, depending on tolerability, had the option to return to KarXT 100/20 BID. Re-escalation to 125/30 BID or re-titration in cases in which the subject had been off KarXT for a longer period of time (at least 7 days) were allowed.
Gastrointestinal disorders
Constipation
18.0%
102/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Diarrhoea
9.2%
52/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Dry mouth
9.4%
53/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Dyspepsia
7.2%
41/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Nausea
23.1%
131/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders
Vomiting
20.0%
113/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations
Weight decreased
5.7%
32/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Dizziness
8.7%
49/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Headache
8.1%
46/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders
Somnolence
6.2%
35/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders
Hyperhidrosis
5.1%
29/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Vascular disorders
Hypertension
10.4%
59/566 • From time of consent to end of study (approximately 400 days)
The number at Risk for All-Cause Mortality, Serious Adverse Events, and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: 1-855-907-3286

Results disclosure agreements

  • Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
  • Publication restrictions are in place

Restriction type: OTHER