Trial Outcomes & Findings for A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-3) (NCT NCT04738123)

NCT ID: NCT04738123

Last Updated: 2024-12-09

Results Overview

The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as the PANSS score at screening.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 256 participants
• Primary outcome timeframe: From baseline up to Week 5
• Results posted on: 2024-12-09

Participant Flow

Participant milestones

Measure	KarXT All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo Participants received matching oral placebo treatment twice per day
Overall Study STARTED	125	131
Overall Study Recieved Treatment	125	128
Overall Study COMPLETED	79	93
Overall Study NOT COMPLETED	46	38

Reasons for withdrawal

Measure	KarXT All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo Participants received matching oral placebo treatment twice per day
Overall Study Changes in condition making participant ineligible for further treatment	1	0
Overall Study Progressive Disease	0	4
Overall Study Adverse Event	8	7
Overall Study Other Reasons	0	1
Overall Study Suicidal or assaultive behavior	0	2
Overall Study Protocol Violation	2	2
Overall Study Consent Withdrawn	35	22

Baseline Characteristics

A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-3)

Baseline characteristics by cohort

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=131 Participants Participants received matching oral placebo treatment twice per day	Total n=256 Participants Total of all reporting groups
Age, Continuous	43.6 Years STANDARD_DEVIATION 11.44 • n=5 Participants	42.6 Years STANDARD_DEVIATION 12.19 • n=7 Participants	43.1 Years STANDARD_DEVIATION 11.82 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	27 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	104 Participants n=7 Participants	191 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	107 Participants n=5 Participants	117 Participants n=7 Participants	224 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	79 Participants n=5 Participants	77 Participants n=7 Participants	156 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	53 Participants n=7 Participants	98 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment

The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as the PANSS score at screening.

Outcome measures

Measure	KarXT n=114 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5	-20.6 Score on a scale Standard Error 1.584	-12.2 Score on a scale Standard Error 1.552

SECONDARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment

PANSS positive score is the sum of all PANSS 7 positive symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility. If a patient has a PANSS assessment recorded and no more than 2 items are missing from the PANSS positive scales, then the PANSS Positive Score will be calculated as the average of the non-missing items multiplied by 7. If 3 or more items are missing (> 30%) at a particular visit, the respective positive score at the visit will not be calculated and will be treated as missing data. Baseline is defined as the PANSS score at screening.

Outcome measures

Measure	KarXT n=114 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5	-7.1 Score on a scale Standard Error 0.499	-3.6 Score on a scale Standard Error 0.492

SECONDARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment

PANSS negative score is the sum of all PANSS 7 negative symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The negative symptoms in schizophrenia are the diminution or loss of normal functions. If a participant has a PANSS assessment recorded, and no more than 2 items are missing from the PANSS negative scales, then the PANSS Negative Score will be calculated as the average of the non-missing items multiplied by 7. If 3 or more items are missing (> 30%) at a particular visit, the respective negative score at the visit will not be calculated and will be treated as missing data. Baseline is defined as the PANSS score at screening.

Outcome measures

Measure	KarXT n=114 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5	-2.7 Score on a scale Standard Error 0.412	-1.8 Score on a scale Standard Error 0.405

SECONDARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment

PANSS Marder factor score is the sum of 5 negative scales and 2 general scales (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance). Participants are rated from 1 to 7 on each symptom scale. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Baseline is defined as the PANSS score at screening.

Outcome measures

Measure	KarXT n=114 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score Change From Baseline at Week 5	-3.5 Score on a scale Standard Error 0.484	-2.7 Score on a scale Standard Error 0.475

SECONDARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment

Clinical Global Impression-Severity (CGI-S) Score is a measurement to evaluate severity and treatment response in schizophrenia. Completed independently by a clinician, the CGI-S assesses extremely ill patients, by asking 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness. The CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients. This scale reflects the total score. Baseline is defined as CGI-S score at screening. The change from baseline in total score is reported.

Outcome measures

Measure	KarXT n=114 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Clinical Global Impression-Severity (CGI-S) Score Change From Baseline at Week 5	-1.1 Score on a scale Standard Error 0.091	-0.6 Score on a scale Standard Error 0.088

SECONDARY outcome

Timeframe: From baseline up to Week 5

Population: All participants who were randomized, received at least 1 dose of study drug, had a baseline PANSS assessment, and had at least 1 post-baseline PANSS assessment, and had a PANSS score at Week 5

Positive and Negative Syndrome Scale (PANSS) is a scale used for measuring symptom severity of subjects with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Subjects are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as screening.

Note: Floor adjusted data were used for this analysis. Floor adjusted total score = total score - 30.

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=91 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Who Achieve >=30% Reduction in Positive and Negative Symptoms Scale (PANSS) Total Score From Baseline to Week 5	40 Participants	23 Participants

SECONDARY outcome

Timeframe: From first dose up to Day 42

Population: All treated participants

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Experiencing Adverse Events (AEs)	88 Participants	64 Participants

SECONDARY outcome

Timeframe: From first dose up to Day 42

Population: All participants who received at least 1 dose of study drug

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

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Experiencing Cholinergic Symptom Adverse Event At Least One Procholinergic Symptom Adverse Event	38 Participants	3 Participants
Number of Participants Experiencing Cholinergic Symptom Adverse Event At Least One Anticholinergic Symptom Adverse Event	33 Participants	8 Participants

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants

The Simpson-Angus Scale (SAS) is an established instrument to measure drug-related extrapyramidal syndromes. It is a 10-item testing instrument used to assess gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. The range of scores is from 0 to 40 with increased scores indicating increased severity. Baseline is defined as the Simpson-Angus Scale score recorded on Day -1.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Simpson-Angus Scale Total Score (SAS)	-0.1 Score on a Scale Standard Deviation 0.56	-0.1 Score on a Scale Standard Deviation 0.36

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable BARS total score at the prespecified timepoint

The BARS for akathisia is a rating scale used to assess the severity of drug-induced akathisia, or restlessness, involuntary movements and inability to sit still. The range of scores is 0 to 14, with higher scores indicating greater severity. Baseline is defined as the BARS score recorded on Day -1.

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=91 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Total Score	-0.1 Score on a Scale Standard Deviation 0.75	-0.1 Score on a Scale Standard Deviation 0.88

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable AIMS total score at the prespecified timepoint

The AIMS is a rating scale that is used to measure involuntary movements known as tardive dyskinesia, which can sometimes develop as a side effect of long-term treatment with antipsychotic medications. This measurement was a 12-item scale to assess orofacial, extremity, and truncal movements as well as the overall severity, incapacitation, and the participant's level of awareness of the movements. Items are scored from 0 (none) to 4 (severe). A higher score indicates more severe dyskinesia. Baseline is defined as the AIMS score recorded on Day -1. The total score is the sum of sub scores for items 1-7. The first 7 items are used to measure the severity of abnormal movements in the orofacial region (4 items: facial muscles, lips, jaw, tongue), upper extremities (1 item), lower extremities (1 item), and trunk (1 item). Change from baseline for the total scores are reported.

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=91 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score	0.0 Units on a Scale Standard Deviation 0.45	0.0 Units on a Scale Standard Deviation 0.15

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable weight values at the prespecified timepoint

The number of participants who lost weight, maintained their weight, or gained weight between baseline and week 5. Baseline is defined as measurements taken at screening.

Outcome measures

Measure	KarXT n=78 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=92 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Who Experienced Weight Change Lost Weight	1 Participants	0 Participants
Number of Participants Who Experienced Weight Change Maintained Weight1	72 Participants	80 Participants
Number of Participants Who Experienced Weight Change Gained Weight	5 Participants	12 Participants

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable BMI values at the prespecified timepoint

The change in Body Mass Index (BMI) from baseline up to week 5. BMI is a person's weight in kilograms divided by the square of height in meters. Baseline is defined as measurements taken at screening.

Outcome measures

Measure	KarXT n=78 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=92 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Body Mass Index (BMI)	0.457 kg/m^2 Standard Deviation 1.1340	0.666 kg/m^2 Standard Deviation 0.570

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable waist circumference values at the prespecified timepoint

The change in waist circumference in centimeters from baseline up to week 5. Baseline is defined as measurements taken at screening.

Outcome measures

Measure	KarXT n=78 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=92 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Waist Circumference	1.666 Centimeters Standard Deviation 4.8915	1.697 Centimeters Standard Deviation 4.8577

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable blood pressure values at the prespecified timepoint

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

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=92 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Orthostatic Vital Signs - Blood Pressure Supine Systolic Blood Pressure	1.9 mmHg Standard Deviation 13.07	0.4 mmHg Standard Deviation 13.00
Change From Baseline in Orthostatic Vital Signs - Blood Pressure Supine Diastolic Blood Pressure	2.2 mmHg Standard Deviation 10.33	0.4 mmHg Standard Deviation 9.30
Change From Baseline in Orthostatic Vital Signs - Blood Pressure Standing Systolic Blood Pressure	2.3 mmHg Standard Deviation 14.07	0.1 mmHg Standard Deviation 12.54
Change From Baseline in Orthostatic Vital Signs - Blood Pressure Standing Diastolic Blood Pressure	2.7 mmHg Standard Deviation 9.93	0.1 mmHg Standard Deviation 8.62

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants with evaluable heart rate values at the prespecified timepoint

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

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=92 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Orthostatic Vital Signs - Heart Rate Supine Heart Rate	11.9 beats/min Standard Deviation 15.72	6.1 beats/min Standard Deviation 14.02
Change From Baseline in Orthostatic Vital Signs - Heart Rate Standing Heart Rate	9.86 beats/min Standard Deviation 16.58	5.8 beats/min Standard Deviation 13.85

SECONDARY outcome

Timeframe: From baseline up to Day 35 or early termination

Population: All treated participants

The change from baseline up to Day 35 or early termination in ECG mean heart rate. Baseline is defined as measurements taken at screening.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate	11.5 beats/min Standard Deviation 14.94	6.1 beats/min Standard Deviation 14.62

SECONDARY outcome

Timeframe: From baseline up to week 5

Population: All treated participants

The number of participants experiencing clinically significant abnormal physical examination results. Baseline is defined as measurements taken at screening.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results General Appearance - Baseline	0 Participants	1 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results General Appearance - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Head, Eyes, Ears, Nose, Throat - Baseline	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Head, Eyes, Ears, Nose, Throat - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Thorax - Baseline	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Thorax - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Abdomen - Baseline	1 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Abdomen - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Cardiac - Baseline	1 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Cardiac - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Musculoskeletal - Baseline	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Musculoskeletal - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Circulatory System - Baseline	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Circulatory System - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Lymphadenopathy - Baseline	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Lymphadenopathy - Day 35	0 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Limited Neurological Examination - Baseline	1 Participants	0 Participants
Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results Limited Neurological Examination - Day 35	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From screening up to Day 42

Population: All participants who had evaluable C-SSRS data.

C-SSRS assesses suicidal behavior and ideation on a scale with 4 general categories: suicidal ideation, intensity of ideation, suicidal behavior, and actual attempts. C-SSRS comprehensively identifies suicidal events while limiting the over identification of suicidal behavior. The C-SSRS was administered by a trained rater at the site.

This study used 2 versions of the C-SSRS. At the Screening Visit, the "Lifetime" version was completed; for all subsequent visits, the "Since Last Visit" version of the C-SSRS was administered.

Risk for suicidal behavior during the study was determined by the investigator's clinical assessment and C-SSRS as confirmed by the following:

• Answering "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episode occurring within the 2 months before screening, or
• Answering "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before screening. Non-suicidal, self-injurious behavior is not exclusionary.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=120 Participants Participants received matching oral placebo treatment twice per day
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation: Participant Wished to be Dead	1 Participants	3 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation: Non-Specific Active Suicidal Thoughts	1 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Most Severe Ideation Level 1. Least Severe	0 Participants	2 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Most Severe Ideation Level 2	1 Participants	0 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Most Severe Ideation Level 3	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation (Frequency) - Less than once a week	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation (Frequency) - Once a week	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation (Frequency) - 2-5 times a week	1 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation (Duration) - Fleeting, a few seconds or minutes	1 Participants	3 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Controllability - Easily able to control thoughts	0 Participants	3 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Controllability - Can control thoughts with little difficulty	1 Participants	0 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Deterrents - Does not apply	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Deterrents - Deterrents definitely stopped participant from attempting suicide	1 Participants	2 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Reasons for Ideation - Does not apply	0 Participants	2 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Reasons for Ideation - Mostly to end or stop the pain	0 Participants	1 Participants
Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS) Reasons for Ideation - Completely to end or stop the pain	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At days 8 and 28

Population: All participants who received at least 1 dose of active study drug and have at least 1 measurable (AUC) plasma concentration of study drug.

AUC is the total area under the plasma drug concentration-time curve from time zero to 12 hours after drug administration. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

Outcome measures

Measure	KarXT n=77 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo Participants received matching oral placebo treatment twice per day
Area Under the Plasma Concentration-Time Curve (AUC) Trospium	27800 h*pg/mL Standard Deviation 26000	—
Area Under the Plasma Concentration-Time Curve (AUC) Xanomeline	50200 h*pg/mL Standard Deviation 37900	—

SECONDARY outcome

Timeframe: At days 8 and 28

Population: All participants who received at least 1 dose of active study drug and have at least 1 measurable (Cmax) plasma concentration of study drug.

Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo Participants received matching oral placebo treatment twice per day
Maximum Concentration (Cmax) Trospium	6070 pg/mL Standard Deviation 7780	—
Maximum Concentration (Cmax) Xanomeline	9660 pg/mL Standard Deviation 10500	—

SECONDARY outcome

Timeframe: At days 8 and 28

Population: a. All participants who received at least 1 dose of active study drug and have at least 1 measurable (Tmax) plasma concentration of study drug.

Tmax is defined as the time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug. Dose level 125/30 BID at Week 4 (Visit 8 [Day 28]) is reported.

Outcome measures

Measure	KarXT n=79 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo Participants received matching oral placebo treatment twice per day
Time to Maximum Concentration (Tmax) Trospium	1.00 Hours Interval 0.0 to 3.95	—
Time to Maximum Concentration (Tmax) Xanomeline	2.00 Hours Interval 0.0 to 12.0	—

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable hemoglobin levels at the specified timepoint

The mean observed Hemoglobin levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

Male: 138 - 172 g/L Female: 121 - 151 g/L

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Hemoglobin Levels Baseline	142.30 g/L Standard Deviation 18.098	142.71 g/L Standard Deviation 15.166
Mean Observed Hemoglobin Levels Week 3 (Visit 7 [Day 21])	144.54 g/L Standard Deviation 19.096	146.27 g/L Standard Deviation 14.335
Mean Observed Hemoglobin Levels Week 5 (Visit 10 [Day 35])/Early-Termination	142.94 g/L Standard Deviation 19.175	144.40 g/L Standard Deviation 15.416

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable hematocrit levels at the specified timepoint

The mean observed Hematocrit levels are displayed in percentages as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

Male: 40.7 - 50.3% Female: 36.1 - 44.3%

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Hematocrit Levels Baseline	44.52 Percentage Standard Deviation 5.232	44.51 Percentage Standard Deviation 4.553
Mean Observed Hematocrit Levels Week 3 (Visit 7 [Day 21])	45.12 Percentage Standard Deviation 5.416	45.25 Percentage Standard Deviation 4.306
Mean Observed Hematocrit Levels Week 5 (Visit 10 [Day 35])/Early-Termination	44.51 Percentage Standard Deviation 5.491	44.71 Percentage Standard Deviation 4.595

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable erythrocyte levels at the specified timepoint

The mean observed erythrocyte levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

Male: 4.7 - 6.1 10^12 cells/L Female: 4.2 - 5.4 10^12 cells/L

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Erythrocyte Levels Baseline	5.025 10^12 cells/L Standard Deviation 0.5072	4.894 10^12 cells/L Standard Deviation 0.4498
Mean Observed Erythrocyte Levels Week 3 (Visit 7 [Day 21])	5.130 10^12 cells/L Standard Deviation 0.4986	5.165 10^12 cells/L Standard Deviation 1.2161
Mean Observed Erythrocyte Levels Week 5 (Visit 10 [Day 35])/Early-Termination	5.058 10^12 cells/L Standard Deviation 0.5339	5.003 10^12 cells/L Standard Deviation 0.5139

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable platelet levels at the specified timepoint

The mean observed platelet levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

150-450 10^9 cells/L

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Platelets Levels Baseline	334.04 10^9 cells/L Standard Deviation 96.465	328.65 10^9 cells/L Standard Deviation 92.288
Mean Observed Platelets Levels Week 3 (Visit 7 [Day 21])	334.47 10^9 cells/L Standard Deviation 80.273	320.21 10^9 cells/L Standard Deviation 73.757
Mean Observed Platelets Levels Week 5 (Visit 10 [Day 35])/Early-Termination	336.59 10^9 cells/L Standard Deviation 88.455	327.91 10^9 cells/L Standard Deviation 75.834

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable leukocytes levels at the specified timepoint

The mean observed leukocytes levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

4.5-10 10^9 cells/L

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Leukocytes Levels Baseline	5.971 10^9 cells/L Standard Deviation 1.9465	6.384 10^9 cells/L Standard Deviation 2.1421
Mean Observed Leukocytes Levels Week 3 (Visit 7 [Day 21])	6.046 10^9 cells/L Standard Deviation 1.8090	6.252 10^9 cells/L Standard Deviation 1.6685
Mean Observed Leukocytes Levels Week 5 (Visit 10 [Day 35])/Early-Termination	6.199 10^9 cells/L Standard Deviation 2.1814	6.184 10^9 cells/L Standard Deviation 1.7208

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable lymphocytes levels at the specified timepoint

The mean observed lymphocytes levels are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Reference Range:

1-4.8 10^9 cells/L

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Lymphocytes Levels Baseline	2.749 10^9 cells/L Standard Deviation 0.9408	3.094 10^9 cells/L Standard Deviation 3.9283
Mean Observed Lymphocytes Levels Week 3 (Visit 7 [Day 21])	2.834 10^9 cells/L Standard Deviation 0.9890	2.976 10^9 cells/L Standard Deviation 0.9431
Mean Observed Lymphocytes Levels Week 5 (Visit 10 [Day 35])/Early-Termination	3.000 10^9 cells/L Standard Deviation 1.2748	2.792 10^9 cells/L Standard Deviation 0.8456

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable activated partial thromboplastin time data at the specified timepoint

The mean observed activated partial thromboplastin times in seconds are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Outcome measures

Measure	KarXT n=124 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=127 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Activated Partial Thromboplastin Time Baseline	30.75 Seconds Standard Deviation 4.412	31.75 Seconds Standard Deviation 5.897
Mean Observed Activated Partial Thromboplastin Time Week 3 (Visit 7 [Day 21])	32.43 Seconds Standard Deviation 4.798	33.55 Seconds Standard Deviation 7.858
Mean Observed Activated Partial Thromboplastin Time Week 5 (Visit 10 [Day 35])/Early-Termination	31.48 Seconds Standard Deviation 3.636	33.04 Seconds Standard Deviation 6.775

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable prothrombin time data at the specified timepoint

The mean observed prothrombin times are displayed as measured at the specified timepoints. Baseline is defined as first dose.

Outcome measures

Measure	KarXT n=123 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=126 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Prothrombin Time Baseline	1.00 Seconds Standard Deviation 0.091	1.01 Seconds Standard Deviation 0.086
Mean Observed Prothrombin Time Week 3 (Visit 7 [Day 21])	1.02 Seconds Standard Deviation 0.096	1.00 Seconds Standard Deviation 0.086
Mean Observed Prothrombin Time Week 5 (Visit 10 [Day 35])/Early-Termination	1.01 Seconds Standard Deviation 0.078	1.00 Seconds Standard Deviation 0.083

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable urine pH data at the specified timepoint

The mean observed pH of participants' urine are displayed as measured at the specified timepoints. Baseline is defined as first dose. Urinalysis was completed using dipstick. Urinalysis was not completed if the local dipstick was normal.

Outcome measures

Measure	KarXT n=89 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=82 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Urinalysis - pH Baseline	5.52 pH Standard Deviation 0.676	5.59 pH Standard Deviation 0.800
Mean Observed Urinalysis - pH Week 3 (Visit 7 [Day 21])	5.33 pH Standard Deviation 0.476	5.48 pH Standard Deviation 0.748
Mean Observed Urinalysis - pH Week 5 (Visit 10 [Day 35]/Early Termination)	5.48 pH Standard Deviation 0.687	5.45 pH Standard Deviation 0.621

SECONDARY outcome

Timeframe: From baseline up to Days 21, 35, or early temination

Population: All treated participants with evaluable urine prolactin data at the specified timepoints

The mean observed prolactin levels of participants' urine are displayed as measured at the specified timepoints. Baseline is defined as first dose. Urinalysis was not completed if the local dipstick was normal.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=122 Participants Participants received matching oral placebo treatment twice per day
Mean Observed Urinalysis - Prolactin Baseline	18.08 ug/L Standard Deviation 21.767	17.38 ug/L Standard Deviation 21.920
Mean Observed Urinalysis - Prolactin Week 3 (Visit 7 [Day 21])	17.49 ug/L Standard Deviation 19.422	14.50 ug/L Standard Deviation 12.064
Mean Observed Urinalysis - Prolactin Week 5 (Visit 10 [Day 35]/Early Termination)	19.46 ug/L Standard Deviation 24.668	15.56 ug/L Standard Deviation 13.463

SECONDARY outcome

Timeframe: At screening, at Dat -1, and upon return from departure from study site at any time up to Day 42

Population: All treated participants

A National Institute on Drug Abuse-5 urine drug screen (cannabinoids or marijuana, phencyclidine, amphetamines, opiates, and cocaine) was performed at screening and at baseline (Visit 2a [Day -1]). If a participant left the study site, they were to have a urine drug screen and test for alcohol (breathalyzer or urine alcohol level) upon returning to the study site.

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
The Number of Participants With Positive Drug Screen Results	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From screening up to Day 42

Population: All treated participants

The liver function test results (ALT, AST, ALP, total bilirubin, GGT) were specifically monitored to watch for any participants who met the FDA drug-induced liver injury (DILI) criteria. A summary of elevated liver function test results by visit is provided. Baseline is defined as measurements taken at screening.

Monitoring for DILI criteria includes close observation initiated with ALT or AST >3 × ULN; discontinuation of treatment should be considered if ALT or AST >8 × ULN, ALT or AST >5 × ULN for more than 2 weeks, ALT or AST >3 × ULN and (total bilirubin >2 × ULN or international normalized ratio >1.5), or ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia (>5%).

Outcome measures

Measure	KarXT n=125 Participants All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 Participants Participants received matching oral placebo treatment twice per day
The Number of Participants With Elevated Liver Function Test Results Visit 4 Day 7 - Gamma Glutamyl Transferase (U/L) > 2 x ULN	0 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 7 Day 21 - Alanine Aminotransferase (U/L) > 3 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Bilirubin (umol/L) > 1. 5 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Gamma Glutamyl Transferase (U/L) > 2 x ULN	4 Participants	4 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Alanine Aminotransferase (U/L) > 3 x ULN	0 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Aspartate Aminotransferase (U/L) > 3 x ULN	0 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Alkaline Phosphatase (U/L) > 105 x ULN	0 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Baseline - Hy's Law Cases	0 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 7 Day 21 - Alanine Aminotransferase (U/L) > 5 x ULN	2 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 7 Day 21 - Aspartate Aminotransferase (U/L) > 3 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 7 Day 21 - Alkaline Phosphatase (U/L) > 2 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 7 Day 21 - Gamma Glutamyl Transferase (U/L) > 2 x ULN	6 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 Day 35 - Alanine Aminotransferase (U/L) > 3 x ULN	0 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 Day 35 - Alanine Aminotransferase (U/L) > 5 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 Day 35 - Alkaline Phosphatase (U/L) > 1. 5 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 Day 35 - Gamma Glutamyl Transferase (U/L) > 2 x ULN	4 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 or Early Termination Alanine Aminotransferase (U/L) >3x ULN	0 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 or Early Termination - Alanine Aminotransferase (U/L) >5x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 or Early Termination - Alkaline Phosphatase (U/L) > 1. 5 x ULN	1 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 or Early Termination - Bilirubin (umol/L) > 2 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 10 or Early Termination - Gamma Glutamyl Transferase (U/L) > 2 x ULN	7 Participants	1 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 11 Day 42 - Bilirubin (umol/L) > 1. 5 x ULN	1 Participants	0 Participants
The Number of Participants With Elevated Liver Function Test Results Visit 11 Day 42 - Gamma Glutamyl Transferase (U/L) > 2 x ULN	3 Participants	0 Participants

Adverse Events

KarXT

Serious events: 1 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	KarXT n=125 participants at risk All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 participants at risk Participants received matching oral placebo treatment twice per day
Gastrointestinal disorders Gastrooesophageal reflux disease	0.80% 1/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	0.00% 0/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.

Other adverse events

Measure	KarXT n=125 participants at risk All participants assigned to KarXT started on a lead-in dose of KarXT 50/20 (xanomeline 50 mg/trospium chloride 20 mg) BID for the first 2 days (Days 1 and 2) followed by KarXT 100/20 (xanomeline 100 mg/trospium chloride 20 mg) BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to KarXT 125/30 BID unless the participant experienced AEs from the previous dose of KarXT 100/20 BID. All participants who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.	Placebo n=128 participants at risk Participants received matching oral placebo treatment twice per day
Gastrointestinal disorders Constipation	12.8% 16/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	3.9% 5/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Gastrointestinal disorders Diarrhoea	5.6% 7/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	0.78% 1/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Gastrointestinal disorders Dyspepsia	16.0% 20/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	1.6% 2/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Gastrointestinal disorders Nausea	19.2% 24/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	1.6% 2/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Gastrointestinal disorders Vomiting	16.0% 20/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	0.78% 1/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Nervous system disorders Headache	11.2% 14/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	11.7% 15/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Psychiatric disorders Anxiety	1.6% 2/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	6.2% 8/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Psychiatric disorders Insomnia	5.6% 7/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	7.8% 10/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.
Vascular disorders Hypertension	6.4% 8/125 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.	1.6% 2/128 • Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 20 months). SAEs and Other AEs were assessed from first dose up to Day 42.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

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

Restriction type: OTHER