Schizophrenia
Conditions
Keywords
BMS-986510, KarXT, DSM-5 Schizophrenia, Diagnostic and Statistical Manual of Mental Disorders, Mental Disorders
Brief summary
The purpose of this study is to assess the safety and efficacy of slowly increasing dose and food effect of KarXT in adult participants with schizophrenia.
Interventions
DRUGKarXT
Specified dose on specified days
Sponsors
Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview (MINI) for Schizophrenia and Psychotic Disorder Studies version 7.0.2. * Positive and Negative Syndrome Scale (PANSS) total score of ≤ 80 at screening and Baseline. * Clinical Global Impression-Severity (CGI-S) score of ≤ 4 at screening and Baseline. * Willing and able to discontinue all antipsychotic medications prior to baseline visit.
Exclusion criteria
* History or presence of clinically significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. * Any primary DSM-5 disorder other than schizophrenia within 12 months before screening. * History of treatment resistance to schizophrenia medications. * History of allergy/hypersensitivity to KarXT. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs From First Dose to End of Study Follow up. | From first dose to end of study follow up (63 days) | Number of participants with Treatment Emergent Adverse Events (TEAEs) from first dose to end of study follow up. An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. |
| Number of Participants With TEAEs at the End of Period 1 and Period 2. | Period 1 (From first dose to day 28) Period 2 (day 29 to day 56) | Number of participants with TEAEs at the end of period 1 and period 2. An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. |
| Number of Participants With Serious TEAEs at the End of Period 1 and Period 2. | Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days) | Number of participants with TEAEs at the end of period 1 and period 2. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization. |
| Number of Participants With TEAEs Leading to Treatment Discontinuation. | Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days) | Number of participants with TEAEs leading to treatment discontinuation. |
| Number of Participants With Pro-cholinergic and Anticholinergic TEAEs. | Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PANSS Total Score, Positive Score and Negative Score | From first dose to end of treatment (56 days) | The Positive and Negative Syndrome Scale (PANSS) assesses schizophrenia symptom severity using 30 items: 7 positive, 7 negative, and 16 general psychopathology scales. Each item is rated from 1 (absent) to 7 (extreme). Positive symptoms represent excesses or distortions of normal function (e.g., hallucinations, delusions), while negative symptoms reflect diminished function. The PANSS positive and negative scores each sum their respective 7 items, ranging from 7 to 49, with higher scores indicating greater severity. The PANSS Total Score sums all 30 items, ranging from 30 to 210, with higher scores reflecting worse overall symptom severity. |
| Change From Baseline in Marder Factor Score. | From first dose to end of treatment (56 days) | 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, with a total score ranging from 7 to 49. 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. |
| Change From Baseline in CGI Severity Score | From first dose to end of treatment (56 days) | Completed independently by a clinician, the CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients, by asking the clinical 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness. |
| Number of Participants With Spontaneously Reported AESIs | From first dose to end of study follow up (63 days) | The AEs of special interest (AESIs) will be monitored and include symptomatic orthostasis, syncope(a transient loss of consciousness or fainting),and liver function test elevations as defined below. For SAE reporting requirements for events of liver injury. |
| Number of Participants With Clinically Significant Changes in Vital Signs | From first dose to end of study follow up (63 days) | Number of participants with clinically significant changes in vital signs |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | From first dose to end of study follow up (63 days) | Number of participants with clinically significant changes in clinical laboratory assessments |
| Number of Participants With Clinically Significant Changes in 12-lead ECGs | From first dose to end of study follow up (63 days) | Number of participants with clinically significant changes in 12-lead ECGs |
| Number of Participants Who Exhibited Suicidal Behavior as Assessed by C-SSRS | From first dose to end of study follow up (63 days) | Number of participants who exhibited suicidal behavior as assessed by C-SSRS |
Countries
United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
100 participants treated in Cohort 1 and 73 Treated in Cohort 2
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 173 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 53 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 73 |
| other Total, other adverse events | 54 / 100 | 44 / 73 |
| serious Total, serious adverse events | 0 / 100 | 0 / 73 |
Outcome results
None listed