Schizophrenia
Conditions
Brief summary
A Phase 3, Multicenter, Two-part Study with a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects with DSM-5 Schizophrenia
Interventions
Oral 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 8-35 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.
DRUGPlacebo
Placebo Capsules
Sponsors
Zai Lab (Shanghai) Co., Ltd.
Karuna Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is Chinese national, aged 18 to 65 years, inclusive, at screening. 2. Subject is capable of providing written informed consent. 3. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 and MINI. 4. Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening. 1. The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms at screen. 2. If already an inpatient at screening, hospitalization has to be ≤2 weeks for the current exacerbation at the time of screening. 5. PANSS total score between 80 and 120,inclusive, with a scores of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items: 1. Item 1 (P1; delusions) 2. Item 2 (P2; conceptual disorganization) 3. Item 3 (P3; hallucinatory behavior) 4. Item 6 (P6; suspiciousness/persecution) 6. Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%. 7. Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits. 8. Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral antipsychotic medications for at least 5 half-lives or 1 week, whichever is longer, before baseline (Day -1). 9. Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA®) before baseline visit (Day -1). 10. Subject is able to be confined to an inpatient setting for the duration of the 5-week double-blind part of the study, follow instructions, and comply with the protocol requirements. 11. Body mass index of 18 to 40 kg/m2, inclusive. 12. Subject resides in a stable living situation and is anticipated to return to that same stable living situation after discharge, in the opinion of the investigator. 13. Subject has an identified reliable informant. An informant is needed at the screening and baseline visits as well as at the end of the study for relevant assessments (site staff may act as informant while the subject is an inpatient). An informant may not be necessary if the subject has been a patient of the investigator for ≥1 year. 14. Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP must be willing and able to adhere to the contraception guidelines.
Exclusion criteria
1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). 2. Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia. 3. 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. 4. Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results. 5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma. 6. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months. 7. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and C-SSRS. 8. Clinically significant abnormal findings on the physical examination, medical history, electrocardiogram, or clinical laboratory results at screening that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results. 9. Subjects are receiving or have recently received (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (e.g., lamotrigine, valproate); tricyclic antidepressants (e.g., imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate). 10. Subjects are receiving or have recently received (within 1 week before baseline \[Day -1\]) metformin. 11. Pregnant, lactating, or less than 3 months postpartum. 12. 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 his/her ability to adhere to the protocol visit schedule or fulfill visit requirements. 13. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening. 14. 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 has required clozapine within the last 12 months. 15. Subjects with prior exposure to KarXT. 16. Subjects who experienced any significant adverse effects due to trospium chloride. 17. Participation in another clinical study within 3 months before screening in which the subject received an experimental or investigational drug agent. 18. Significant risk of violent or destructive behavior.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
| Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes. 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. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
| Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
| Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period | At Baseline and at Week 12 of the Open-Label Period | PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | From first dose until study completion (up to approximately 18 weeks) | Adverse Event (AE): An AE is any unfavorable and unintended sign, symptom, or disease that occurs in a participant during a clinical trial, regardless of whether it is related to the study treatment. This includes new conditions or worsening of pre-existing ones. Serious Adverse Event (SAE): An SAE is an AE that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, causes persistent or significant disability/incapacity, or leads to a congenital anomaly/birth defect. Other events may be considered serious if they require medical intervention to prevent one of these outcomes. |
| Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | At Baseline and at Week 5 of the Double-Blind Period | The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug. |
| Number of Participants With Elevated Liver Function Test Results | At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks) | ULN = upper limit of normal range.; DB = Double-blind period; OL = Open-label period. Hy's law is defined as an elevated alanine aminotransferase level (\>3xULN) or an elevated aspartate aminotransferase (\>3xULN) in combination with alkaline phosphatase \<2xULN and elevated total bilirubin (\>2 x ULN). Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Number of Participants With Elevated Metabolic Syndrome Parameters | At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks) | ULN = Upper limit of normal; DB = Double-blind period; OL = Open-label period. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Results | At study baseline and up to study completion (up to approximately 18 weeks) | Anytime post-baseline includes all assessments from the first dose of study drug until end of study visit in double-blind/open-label part, including unscheduled assessments. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | From first dose to study completion (up to approximately 18 weeks) | The C-SSRS is a clinician- or self-administered questionnaire assessing suicidal ideation and behavior. It rates ideation severity from 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). It also records the presence or absence of suicidal behaviors, including actual, interrupted, or aborted attempts, and preparatory acts. The highest level of ideation or most severe behavior reported is used to determine suicide risk; higher ideation scores or any suicidal behavior indicate greater risk. Baseline is the last non-missing assessment before first study drug dose. |
| Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | At study baseline, open-label baseline, and up to study completion (up to approximately 18 weeks) | Treatment-emergent parkinsonism is defined as Simpson-Angus Scale total score \>3 with a baseline score ≤3. Treatment-emergent akathisia is defined as Barnes Akathisia Rating Scale global clinical assessment score \>2 with a baseline score ≤2. Treatment-emergent dyskinesia is defined as any Abnormal Involuntary Movement Scale (AIMS) item 1-7 score ≥3 with a baseline score \<3 for the item, or score ≥2 on two or more of AIMS items 1-7 with baseline \<2 for the items. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Body Weight | At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks) | Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period | On Day 28 of the Double-Blind Period | Cmax is the highest concentration of a drug measured in the blood after it is given. |
| Change From Baseline in Body Mass Index (BMI) | At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks) | Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Change From Baseline in Waist Circumference | At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 months) | Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part. |
| Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period | On Day 28 of the Double-Blind Period | AUC₀-12 (Area Under the Concentration-Time Curve from time zero to 12 hours) is the total amount of drug in the blood measured from the time the drug is given (time zero) up to 12 hours after dosing. |
| Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period | On Day 28 of the Double-Blind Period | Tmax is the amount of time it takes to reach that highest concentration (Cmax) after the drug is given. |
| Number of Participants With Orthostatic Vital Sign Events | From first dose until study completion (up to approximately 18 weeks) | Orthostatic vital signs included blood pressure and heart rate. A participant having sustained orthostatic event is defined as the participant experienced at least one orthostatic event for at least 3 consecutive visits. |
Countries
China
Participant flow
Pre-assignment details
Participants completed 5-week KarXT treatment in the double-blind period and signed ICF for the open-label extension period continued KarXT treatment to additional 12-week.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Part: KarXT Participants received oral Capsule KarXT (xanomeline 125 mg/trospium 30 mg BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium 30 mg BID unless the participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium 20 mg BID. All participants who were increased to xanomeline 125 mg/trospium 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium 20 mg BID for the first 3 week of the treatment period. | 103 |
| Double-Blind Part: Placebo Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks. | 99 |
| Open-Label Part: KarXT/KarXT Participants completed 5-week KarXT treatment in the double-blind part and signed ICF for the open-label part. Participants continued oral Capsule KarXT (xanomeline 125 mg/trospium 30 mg BID) in a long-term treatment period of 12 weeks. In the open-label part, participants were started on a lead in dose of xanomeline 50 mg/trospium 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium 20 mg BID for the remainder of Week (Days 3 to 7) of the open-label part. On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium 30 mg BID unless the participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium 20 mg BID. All participants who were increased to xanomeline 125 mg/trospium 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium 20 mg BID for the remainder of the treatment period. | 0 |
| Open-Label Part: Placebo/KarXT Participants completed 5-week matching placebo to KarXT in the double-blind part and signed ICF for the open-label part. Participants continued oral Capsule KarXT (xanomeline 125 mg/trospium 30 mg BID) in a long-term treatment period of 12 weeks. In the open-label part, participants were started on a lead in dose of xanomeline 50 mg/trospium 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium 20 mg BID for the remainder of Week (Days 3 to 7) of the open-label part. On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium 30 mg BID unless the participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium 20 mg BID. All participants who were increased to xanomeline 125 mg/trospium 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium 20 mg BID for the remainder of the treatment period. | 0 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 8 | 9 | 0 | 0 |
| Double-Blind Period | Other reasons | 2 | 3 | 0 | 0 |
| Double-Blind Period | Participant withdrew consent | 11 | 7 | 0 | 0 |
| Double-Blind Period | Protocol Violation | 2 | 1 | 0 | 0 |
| Open Label Period | Adverse Event | 0 | 0 | 2 | 4 |
| Open Label Period | Death | 0 | 0 | 0 | 1 |
| Open Label Period | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Open Label Period | Other reasons | 0 | 0 | 9 | 5 |
| Open Label Period | Participant withdrew consent | 0 | 0 | 8 | 6 |
| Open Label Period | Protocol Violation | 0 | 0 | 0 | 1 |
| Pre-Treatment Period | Protocol Violation | 0 | 1 | 0 | 0 |
| Pre-Treatment Period | Screen failure | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-Blind Part: Placebo | Total | Double-Blind Part: KarXT |
|---|---|---|---|
| Age, Continuous | 36.9 Years STANDARD_DEVIATION 11.91 | 37.1 Years STANDARD_DEVIATION 10.75 | 37.3 Years STANDARD_DEVIATION 9.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 202 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 99 Participants | 202 Participants | 103 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 50 Participants | 106 Participants | 56 Participants |
| Sex: Female, Male Male | 49 Participants | 96 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 99 | 0 / 38 | 1 / 28 |
| other Total, other adverse events | 97 / 102 | 90 / 98 | 33 / 38 | 28 / 28 |
| serious Total, serious adverse events | 0 / 102 | 3 / 98 | 0 / 38 | 3 / 28 |
Outcome results
Primary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period
PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment in the double-blind period. Prespecified to be reported for the double-blind period only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period | -16.9 Score on a Scale | Standard Error 2.122 |
| Double-Blind Part: Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period | -7.7 Score on a Scale | Standard Error 2.074 |
p-value: 0.001495% CI: [-14.8, -3.6]Mixed model repeated measure
Secondary
Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period
AUC₀-12 (Area Under the Concentration-Time Curve from time zero to 12 hours) is the total amount of drug in the blood measured from the time the drug is given (time zero) up to 12 hours after dosing.
Time frame: On Day 28 of the Double-Blind Period
Population: All treated participants who received at least one dose of study medicine in the double-blind period and who have available PK data. Prespecified to be reported for the Double-Blind Period only. participants who received treatment are not mutually exclusive
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 100/20 | 93200 pg*h/mL | Geometric Coefficient of Variation 89.9 |
| Double-Blind Part: KarXT | Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 125/30 | 87100 pg*h/mL | Geometric Coefficient of Variation 75.9 |
| Double-Blind Part: KarXT | Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 100/20 | 48600 pg*h/mL | Geometric Coefficient of Variation 70.4 |
| Double-Blind Part: KarXT | Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 125/30 | 47900 pg*h/mL | Geometric Coefficient of Variation 81.9 |
Secondary
Change From Baseline in Body Mass Index (BMI)
Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods with baseline and at least one post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Body Mass Index (BMI) | Day 35/Week 5 Change from Study baseline | -0.79 Kg/m2 | Standard Deviation 1.106 |
| Double-Blind Part: KarXT | Change From Baseline in Body Mass Index (BMI) | End of Study Change from Study baseline | -1.01 Kg/m2 | Standard Deviation 1.133 |
| Double-Blind Part: Placebo | Change From Baseline in Body Mass Index (BMI) | Day 35/Week 5 Change from Study baseline | -0.43 Kg/m2 | Standard Deviation 1.135 |
| Double-Blind Part: Placebo | Change From Baseline in Body Mass Index (BMI) | End of Study Change from Study baseline | -0.22 Kg/m2 | Standard Deviation 1.193 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Mass Index (BMI) | Day 84/Week 12 Change from open-label baseline | -0.46 Kg/m2 | Standard Deviation 2.121 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Mass Index (BMI) | Day 84/Week 12 Change from Study baseline | -1.10 Kg/m2 | Standard Deviation 2.692 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Mass Index (BMI) | End of Study Change from Study baseline | -0.92 Kg/m2 | Standard Deviation 2.499 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Mass Index (BMI) | End of Study Change from open-label baseline | -0.52 Kg/m2 | Standard Deviation 2.046 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Mass Index (BMI) | Day 84/Week 12 Change from Study baseline | -2.61 Kg/m2 | Standard Deviation 1.983 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Mass Index (BMI) | Day 84/Week 12 Change from open-label baseline | 1.59 Kg/m2 | Standard Deviation 1.276 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Mass Index (BMI) | End of Study Change from open-label baseline | -1.05 Kg/m2 | Standard Deviation 1.224 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Mass Index (BMI) | End of Study Change from Study baseline | -1.83 Kg/m2 | Standard Deviation 1.93 |
Secondary
Change From Baseline in Body Weight
Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods with baseline and at least one post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Body Weight | Day 35 change from study baseline | -2.125 Kg | Standard Deviation 2.9596 |
| Double-Blind Part: KarXT | Change From Baseline in Body Weight | End of study change from study baseline | -2.773 Kg | Standard Deviation 3.1119 |
| Double-Blind Part: Placebo | Change From Baseline in Body Weight | Day 35 change from study baseline | -1.184 Kg | Standard Deviation 3.1079 |
| Double-Blind Part: Placebo | Change From Baseline in Body Weight | End of study change from study baseline | -0.646 Kg | Standard Deviation 3.3921 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Weight | Day 84 change from open-label baseline | -1.222 Kg | Standard Deviation 5.2847 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Weight | Day 84 change from study baseline | -2.889 Kg | Standard Deviation 6.7846 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Weight | End of study change from study baseline | -2.533 Kg | Standard Deviation 6.4198 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Body Weight | End of study change from open-label baseline | -1.462 Kg | Standard Deviation 5.1589 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Weight | Day 84 change from study baseline | -6.955 Kg | Standard Deviation 5.0021 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Weight | Day 84 change from open-label baseline | -4.182 Kg | Standard Deviation 2.9634 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Weight | End of study change from open-label baseline | -2.850 Kg | Standard Deviation 3.2432 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Body Weight | End of study change from study baseline | -4.995 Kg | Standard Deviation 5.2225 |
Secondary
Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period
The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/open-label period baseline and least 1 post-baseline CGI-S assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -1.1 Score on a Scale | Standard Deviation 1.06 |
| Double-Blind Part: KarXT | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.1 Score on a Scale | Standard Deviation 0.8 |
| Double-Blind Part: Placebo | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -1.2 Score on a Scale | Standard Deviation 0.98 |
| Double-Blind Part: Placebo | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.5 Score on a Scale | Standard Deviation 0.82 |
Secondary
Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period
The CGI-S Score is a clinician-rated scale used to assess the severity of a patient's mental illness at a given time. It ranges from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). The score reflects the clinician's overall impression based on observed symptoms, behavior, and functioning. Higher scores indicate greater illness severity and worse clinical status. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline CGI-S assessment in the double-blind period. Prespecified to be reported for the double-blind period only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period | -0.9 Score on a Scale | Standard Error 0.119 |
| Double-Blind Part: Placebo | Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period | -0.5 Score on a Scale | Standard Error 0.117 |
p-value: 0.020895% CI: [-0.7, -0.1]Mixed model for repeated measures
Secondary
Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period
The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/open-label period baseline and least 1 post-baseline PANSS assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -3.9 Score on a Scale | Standard Deviation 7.4 |
| Double-Blind Part: KarXT | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.2 Score on a Scale | Standard Deviation 5.43 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -3.0 Score on a Scale | Standard Deviation 7.25 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.8 Score on a Scale | Standard Deviation 4.49 |
Secondary
Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
The Negative Marder Factor Score is subset of PANSS items used to evaluate negative symptoms based on a five-factor model. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity, motor retardation, and active social avoidance. Each item is rated from 1 to 7. Higher scores reflect greater severity of negative symptoms and poorer clinical outcomes. 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. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment in the double-blind period. Prespecified to be reported for the double-blind period only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -3.1 Score on a Scale | Standard Error 0.677 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -0.5 Score on a Scale | Standard Error 0.66 |
p-value: 0.005695% CI: [-4.3, -0.8]Mixed model for Repeated measures
Secondary
Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period
The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/open-label period baseline and least 1 post-baseline PANSS assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -4.3 Score on a Scale | Standard Deviation 7.75 |
| Double-Blind Part: KarXT | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.4 Score on a Scale | Standard Deviation 5.64 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -3.0 Score on a Scale | Standard Deviation 7.4 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -1.4 Score on a Scale | Standard Deviation 4.88 |
Secondary
Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
The Positive and Negative Syndrome Scale (PANSS) Negative Symptom Score assesses the severity of negative symptoms in schizophrenia, such as emotional withdrawal and reduced motivation. It includes 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity, and stereotyped thinking. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment in the double-blind period. Prespecified to be reported for the double-blind period only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -3.2 Score on a Scale | Standard Error 0.664 |
| Double-Blind Part: Placebo | Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -0.7 Score on a Scale | Standard Error 0.648 |
p-value: 0.006295% CI: [-4.2, -0.7]Mixed model for Repeated measures
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period
PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/open-label period baseline and least 1 post-baseline PANSS assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -22.0 Score on a Scale | Standard Deviation 21.67 |
| Double-Blind Part: KarXT | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -2.7 Score on a Scale | Standard Deviation 17.27 |
| Double-Blind Part: Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | -21.2 Score on a Scale | Standard Deviation 19.76 |
| Double-Blind Part: Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -6.1 Score on a Scale | Standard Deviation 12.49 |
Secondary
Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period
The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/open-label period baseline and least 1 post-baseline PANSS assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period - Week 12 | -6.9 Score on a Scale | Standard Deviation 6.09 |
| Double-Blind Part: KarXT | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.2 Score on a Scale | Standard Deviation 5.31 |
| Double-Blind Part: Placebo | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Study baseline to Open-label period - Week 12 | -8.2 Score on a Scale | Standard Deviation 6.65 |
| Double-Blind Part: Placebo | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | -0.8 Score on a Scale | Standard Deviation 4.64 |
Secondary
Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
The PANSS Positive Symptom Score assesses the severity of positive symptoms in schizophrenia, such as hallucinations and delusions. It includes 7 items: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Each item is rated from 1 (absent) to 7 (extreme), for a total score range of 7 to 49. Higher scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment in the double-blind period. Prespecified to be collected for the double-blind period only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -6.5 Score on a Scale | Standard Error 0.713 |
| Double-Blind Part: Placebo | Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period | -4.6 Score on a Scale | Standard Error 0.7 |
p-value: 0.047495% CI: [-3.8, 0]Mixed model for Repeated measures
Secondary
Change From Baseline in Waist Circumference
Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 months)
Population: All treated participants in the double blind/open-label periods with baseline and at least one post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Change From Baseline in Waist Circumference | Day 35/Week 5 Change from Study baseline | -2.27 cm | Standard Deviation 4.07 |
| Double-Blind Part: KarXT | Change From Baseline in Waist Circumference | End of Study Change from Study baseline | -3.40 cm | Standard Deviation 4.155 |
| Double-Blind Part: Placebo | Change From Baseline in Waist Circumference | Day 35/Week 5 Change from Study baseline | -1.01 cm | Standard Deviation 3.269 |
| Double-Blind Part: Placebo | Change From Baseline in Waist Circumference | End of Study Change from Study baseline | -1.34 cm | Standard Deviation 4.167 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Waist Circumference | Day 84/Week 12 Change from open-label baseline | -1.88 cm | Standard Deviation 7.198 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Waist Circumference | Day 84/Week 12 Change from Study baseline | -3.96 cm | Standard Deviation 8.288 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Waist Circumference | End of Study Change from Study baseline | -4.69 cm | Standard Deviation 8.183 |
| Open-Label Part: KarXT/KarXT | Change From Baseline in Waist Circumference | End of Study Change from open-label baseline | -3.12 cm | Standard Deviation 6.874 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Waist Circumference | Day 84/Week 12 Change from Study baseline | -4.82 cm | Standard Deviation 6.416 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Waist Circumference | Day 84/Week 12 Change from open-label baseline | -2.27 cm | Standard Deviation 4.671 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Waist Circumference | End of Study Change from open-label baseline | -2.45 cm | Standard Deviation 2.543 |
| Open-Label Part: Placebo/KarXT | Change From Baseline in Waist Circumference | End of Study Change from Study baseline | -3.39 cm | Standard Deviation 5.345 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period
Cmax is the highest concentration of a drug measured in the blood after it is given.
Time frame: On Day 28 of the Double-Blind Period
Population: All treated participants who received at least one dose of study medicine in the double-blind period and who have available PK data. Prespecified to be reported for the Double-Blind Period only. Participants who received treatment are not mutually exclusive
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Part: KarXT | Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 100/20 | 16000 pg/mL | Geometric Coefficient of Variation 129.1 |
| Double-Blind Part: KarXT | Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 125/30 | 15900 pg/mL | Geometric Coefficient of Variation 95.9 |
| Double-Blind Part: KarXT | Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 100/20 | 11100 pg/mL | Geometric Coefficient of Variation 139.7 |
| Double-Blind Part: KarXT | Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 125/30 | 9330 pg/mL | Geometric Coefficient of Variation 99.3 |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Results
Anytime post-baseline includes all assessments from the first dose of study drug until end of study visit in double-blind/open-label part, including unscheduled assessments. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline and up to study completion (up to approximately 18 weeks)
Population: All treated participants with available baseline and at least one post-baseline ECG result in the double blind/open-label periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 450 msec | 3 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 450 msec | 2 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - PR ≥ 250 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - PR ≥ 250 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from study baseline | 2 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from study baseline | 17 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 480 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QRS Interval ≥ 150 msec | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 500 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 480 msec | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 500 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - PR ≥ 250 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 450 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 480 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 500 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - PR ≥ 250 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 450 msec | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 480 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 500 msec | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from study baseline | 21 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from study baseline | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - PR ≥ 250 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 450 msec | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 480 msec | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 480 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from open-label baseline | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 500 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from study baseline | 4 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 450 msec | 3 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from study baseline | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from open-label baseline | 4 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - PR ≥ 250 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 500 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from study baseline | 6 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 450 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 480 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - PR ≥ 250 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - PR ≥ 250 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 480 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from study baseline | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 500 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 30 msec from open-label baseline | 6 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF > 500 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Baseline - QTcF > 450 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QRS Interval ≥ 150 msec | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Abnormal Electrocardiogram (ECG) Results | Anytime post baseline - QTcF Increase > 60 msec from open-label baseline | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal
Adverse Event (AE): An AE is any unfavorable and unintended sign, symptom, or disease that occurs in a participant during a clinical trial, regardless of whether it is related to the study treatment. This includes new conditions or worsening of pre-existing ones. Serious Adverse Event (SAE): An SAE is an AE that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, causes persistent or significant disability/incapacity, or leads to a congenital anomaly/birth defect. Other events may be considered serious if they require medical intervention to prevent one of these outcomes.
Time frame: From first dose until study completion (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events | 97 Participants |
| Double-Blind Part: KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events leading to drug withdrawal | 8 Participants |
| Double-Blind Part: KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Serious adverse events | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events | 90 Participants |
| Double-Blind Part: Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events leading to drug withdrawal | 9 Participants |
| Double-Blind Part: Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Serious adverse events | 3 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Serious adverse events | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events | 33 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events leading to drug withdrawal | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events | 28 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Adverse events leading to drug withdrawal | 4 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal | Serious adverse events | 3 Participants |
Secondary
Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results
Treatment-emergent parkinsonism is defined as Simpson-Angus Scale total score \>3 with a baseline score ≤3. Treatment-emergent akathisia is defined as Barnes Akathisia Rating Scale global clinical assessment score \>2 with a baseline score ≤2. Treatment-emergent dyskinesia is defined as any Abnormal Involuntary Movement Scale (AIMS) item 1-7 score ≥3 with a baseline score \<3 for the item, or score ≥2 on two or more of AIMS items 1-7 with baseline \<2 for the items. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, open-label baseline, and up to study completion (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods with baseline and at least one post-baseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respect to study baseline | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to study baseline | 2 Participants |
| Double-Blind Part: KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to study baseline | 3 Participants |
| Double-Blind Part: Placebo | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respect to study baseline | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to study baseline | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to study baseline | 3 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to study baseline | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to study baseline | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respect to study baseline | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to open-label baseline | 2 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to open-label baseline | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respects to open-label baseline | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to open-label baseline | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Akathisia with respect to study baseline | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to study baseline | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Parkinsonism with respect to open-label baseline | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respects to open-label baseline | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results | Treatment-Emergent Dyskinesia with respect to study baseline | 1 Participants |
Secondary
Number of Participants With Elevated Liver Function Test Results
ULN = upper limit of normal range.; DB = Double-blind period; OL = Open-label period. Hy's law is defined as an elevated alanine aminotransferase level (\>3xULN) or an elevated aspartate aminotransferase (\>3xULN) in combination with alkaline phosphatase \<2xULN and elevated total bilirubin (\>2 x ULN). Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks)
Population: All treated participants with baseline and at least one post baseline liver function assessment in the double blind/open-label periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >3XULN | 5 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >5XULN | 2 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >8XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >3XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >5XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB- Aspartate Aminotransferase - >8XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >10XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alkaline phosphatase - >1.5XULN | 2 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Bilirubin - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Gamma glutamyl transferase - >2XULN | 9 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Hy's law cases | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Hy's law cases | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Gamma glutamyl transferase - >2XULN | 3 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Hy's law cases | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Bilirubin - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >1.5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Hy's law cases | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >1.5XULN | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Hy's law cases | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB- Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Bilirubin - >1.5XULN | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 21 DB - Hy's law cases | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >3XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alkaline phosphatase - >1.5XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Alkaline phosphatase - >2XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Hy's law cases | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Bilirubin - >1.5XULN | 4 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | Day 35 DB - Gamma glutamyl transferase - >2XULN | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >1.5XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >1.5XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >2XULN | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Liver Function Test Results | End of study - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >3XULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Hy's law cases | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Gamma glutamyl transferase - >2XULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Hy's law cases | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | End of study - Hy's law cases | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Open-label baseline - Hy's law cases | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Bilirubin - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 14 OL - Hy's law cases | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Hy's law cases | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Gamma glutamyl transferase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >8XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Bilirubin - >1.5XULN | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >2XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Alanine aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Alkaline phosphatase - >1.5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >3XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >20XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >5XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Study Baseline - Aspartate Aminotransferase - >10XULN | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Liver Function Test Results | Day 84 - OL - Aspartate Aminotransferase - >8XULN | 0 Participants |
Secondary
Number of Participants With Elevated Metabolic Syndrome Parameters
ULN = Upper limit of normal; DB = Double-blind period; OL = Open-label period. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks)
Population: All treated participants with baseline and at least one post-baseline result in the double blind/open-label periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Glucose > ULN | 6 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Total Cholesterol > ULN | 5 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Total Cholesterol > ULN | 19 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Glucose > ULN | 14 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Triglycerides > ULN | 8 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Triglycerides > ULN | 18 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Glucose > ULN | 10 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Total Cholesterol > ULN | 7 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Triglycerides > ULN | 19 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Glucose > ULN | 12 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Total Cholesterol > ULN | 7 Participants |
| Double-Blind Part: KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Triglycerides > ULN | 18 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Total Cholesterol > ULN | 8 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Glucose > ULN | 7 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Triglycerides > ULN | 14 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Glucose > ULN | 8 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Glucose > ULN | 12 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Total Cholesterol > ULN | 11 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Total Cholesterol > ULN | 6 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 35 DB - Triglycerides > ULN | 25 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 21 DB - Triglycerides > ULN | 22 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Triglycerides > ULN | 20 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Glucose > ULN | 18 Participants |
| Double-Blind Part: Placebo | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Total Cholesterol > ULN | 4 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Total Cholesterol > ULN | 6 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Glucose > ULN | 6 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Triglycerides > ULN | 5 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Glucose > ULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Total Cholesterol > ULN | 4 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Triglycerides > ULN | 2 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Glucose > ULN | 6 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Total Cholesterol > ULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Triglycerides > ULN | 9 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Glucose > ULN | 5 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Total Cholesterol > ULN | 3 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Triglycerides > ULN | 8 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Glucose > ULN | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Total Cholesterol > ULN | 2 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Triglycerides > ULN | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Total Cholesterol > ULN | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Triglycerides > ULN | 3 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Triglycerides > ULN | 6 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Total Cholesterol > ULN | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Glucose > ULN | 3 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Triglycerides > ULN | 8 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Glucose > ULN | 5 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Total Cholesterol > ULN | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Total Cholesterol > ULN | 5 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Study baseline - Glucose > ULN | 8 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Glucose > ULN | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | End of study - Triglycerides > ULN | 4 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 14 OL - Total Cholesterol > ULN | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Open-label baseline - Glucose > ULN | 3 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Elevated Metabolic Syndrome Parameters | Day 84 OL - Triglycerides > ULN | 2 Participants |
Secondary
Number of Participants With Orthostatic Vital Sign Events
Orthostatic vital signs included blood pressure and heart rate. A participant having sustained orthostatic event is defined as the participant experienced at least one orthostatic event for at least 3 consecutive visits.
Time frame: From first dose until study completion (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Systolic Blood Pressure of ≥ 20 mmHg | 21 Participants |
| Double-Blind Part: KarXT | Number of Participants With Orthostatic Vital Sign Events | Orthostatic event at any visit | 36 Participants |
| Double-Blind Part: KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Diastolic Blood Pressure of ≥ 10 mmHg | 16 Participants |
| Double-Blind Part: KarXT | Number of Participants With Orthostatic Vital Sign Events | Sustained orthostatic events | 3 Participants |
| Double-Blind Part: KarXT | Number of Participants With Orthostatic Vital Sign Events | An Increase in Heart Rate of ≥ 30 bpm | 9 Participants |
| Double-Blind Part: Placebo | Number of Participants With Orthostatic Vital Sign Events | An Increase in Heart Rate of ≥ 30 bpm | 12 Participants |
| Double-Blind Part: Placebo | Number of Participants With Orthostatic Vital Sign Events | Orthostatic event at any visit | 31 Participants |
| Double-Blind Part: Placebo | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Systolic Blood Pressure of ≥ 20 mmHg | 10 Participants |
| Double-Blind Part: Placebo | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Diastolic Blood Pressure of ≥ 10 mmHg | 16 Participants |
| Double-Blind Part: Placebo | Number of Participants With Orthostatic Vital Sign Events | Sustained orthostatic events | 2 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Orthostatic Vital Sign Events | Sustained orthostatic events | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Diastolic Blood Pressure of ≥ 10 mmHg | 4 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Orthostatic Vital Sign Events | An Increase in Heart Rate of ≥ 30 bpm | 2 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Orthostatic Vital Sign Events | Orthostatic event at any visit | 8 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Systolic Blood Pressure of ≥ 20 mmHg | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Orthostatic Vital Sign Events | An Increase in Heart Rate of ≥ 30 bpm | 0 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Systolic Blood Pressure of ≥ 20 mmHg | 2 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Orthostatic Vital Sign Events | A Decrease in Diastolic Blood Pressure of ≥ 10 mmHg | 5 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Orthostatic Vital Sign Events | Orthostatic event at any visit | 5 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Orthostatic Vital Sign Events | Sustained orthostatic events | 0 Participants |
Secondary
Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater
The C-SSRS is a clinician- or self-administered questionnaire assessing suicidal ideation and behavior. It rates ideation severity from 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). It also records the presence or absence of suicidal behaviors, including actual, interrupted, or aborted attempts, and preparatory acts. The highest level of ideation or most severe behavior reported is used to determine suicide risk; higher ideation scores or any suicidal behavior indicate greater risk. Baseline is the last non-missing assessment before first study drug dose.
Time frame: From first dose to study completion (up to approximately 18 weeks)
Population: All treated participants in the double blind/open-label periods with baseline and at least one post-baseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation (SI) - Any Suicidal Ideation | 7 Participants |
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Wish to be Dead | 5 Participants |
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Non-Specific Active Suicidal Thoughts | 6 Participants |
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with any Methods without Intent to Act | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with Some Intent to Act without Specific Plan | 1 Participants |
| Double-Blind Part: KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Active Suicidal Ideation with Specific Plan and Intent | 1 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Active Suicidal Ideation with Specific Plan and Intent | 0 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with any Methods without Intent to Act | 2 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation (SI) - Any Suicidal Ideation | 4 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Non-Specific Active Suicidal Thoughts | 3 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Wish to be Dead | 4 Participants |
| Double-Blind Part: Placebo | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with Some Intent to Act without Specific Plan | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Wish to be Dead | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Non-Specific Active Suicidal Thoughts | 1 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with any Methods without Intent to Act | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Active Suicidal Ideation with Specific Plan and Intent | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with Some Intent to Act without Specific Plan | 0 Participants |
| Open-Label Part: KarXT/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation (SI) - Any Suicidal Ideation | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with Some Intent to Act without Specific Plan | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Active Suicidal Ideation with Specific Plan and Intent | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Wish to be Dead | 3 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline SI - Active Suicidal Ideation with any Methods without Intent to Act | 1 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation (SI) - Any Suicidal Ideation | 3 Participants |
| Open-Label Part: Placebo/KarXT | Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater | Post-Baseline Suicidal ideation - Non-Specific Active Suicidal Thoughts | 1 Participants |
Secondary
Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period
PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Study baseline is defined as last non-missing assessment prior to the first dose of study drug. Open-label baseline is defined as last non-missing assessment prior to the first dose of study drug in the open-label part.
Time frame: At Baseline and at Week 12 of the Open-Label Period
Population: All participants who received at least one dose of study medicine in the open-label period and had study/Open-label period baseline and least 1 post-baseline PANSS assessment in the Open-label Period. Prespecified to be reported for the open-label period only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Part: KarXT | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | 66.7 Percentage of participants |
| Double-Blind Part: KarXT | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | 16.7 Percentage of participants |
| Double-Blind Part: Placebo | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period | Study baseline to Open-label period- Week 12 | 45.5 Percentage of participants |
| Double-Blind Part: Placebo | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period | Open-label period- baseline to Open-label period- Week 12 | 27.3 Percentage of participants |
Secondary
Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period
PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.
Time frame: At Baseline and at Week 5 of the Double-Blind Period
Population: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment (≥30% Change) in the double-blind period. Prespecified to be reported for the double-blind period only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Part: KarXT | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period | 42.1 Percentage of participants |
| Double-Blind Part: Placebo | Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period | 26.3 Percentage of participants |
p-value: 0.040295% CI: [0.7, 29.9]Chi-squared
Secondary
Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period
Tmax is the amount of time it takes to reach that highest concentration (Cmax) after the drug is given.
Time frame: On Day 28 of the Double-Blind Period
Population: All treated participants who received at least one dose of study medicine in the double-blind period and who have available PK data. Prespecified to be reported for the Double-Blind Period only. participants who received treatment are not mutually exclusive
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Double-Blind Part: KarXT | Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 100/20 | 1.70 Hours |
| Double-Blind Part: KarXT | Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Xanomeline 125/30 | 1.93 Hours |
| Double-Blind Part: KarXT | Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 100/20 | 0.56 Hours |
| Double-Blind Part: KarXT | Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period | Day 28 - Trospium 125/30 | 0.97 Hours |