Inclusion Criteria:  Subject is aged 18 to 55 years at Screening Subject is capable of providing signed electronic Informed Consent Form (eICF) before any study assessments will be performed. If local regulations do not allow eICF, then paper ICFs are permitted Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2 Subject is currently being treated with monotherapy risperidone, paliperidone, aripiprazole, quetiapine, ziprasidone or lurasidone and has been taking this treatment with the same dosing regimen for at least 8 weeks at the time of Screening (supported by documentation) The subject has had at least 1 previous inadequate response to above antipsychotics that was dosed appropriately (within the label) for at least 6 weeks The subject has not required psychiatric hospitalization, incarceration in prison, acute crisis intervention, or other increase in the level of care due to symptom exacerbation within 8 weeks of Screening and is psychiatrically stable in the opinion of the Investigator Quetiapine, up to 200 mg at bedtime, may be used to treat insomnia if started at least 8 weeks prior to Screening To be eligible for randomization, subjects will need 80% adherence with their prescribed antipsychotic dosing using AiCure technology and pill count during the Screening period. For subjects currently on long-acting injectables, AiCure will not be used in the Screening phase. For subjects on long-acting injectables it will be sufficient to obtain confirmation that the subject is within the treatment window Positive and Negative Syndrome Scale (PANSS) total score ≥ 70 at Screening (Visit 1) and randomization (Day 1, Visit 3) Clinical Global Impression-Severity (CGI-S) scale with a score ≥ 4 (moderate) at Screening and randomization PANSS Marder Positive symptom factor ≥ 4 on two items (PANSS items, delusions, hallucinations, grandiosity, suspiciousness and persecution, stereotyped thinking, somatic concern, unusual thought content or lack of judgment and insight), at Screening (Visit 1) and randomization (Day 1, Visit 3) Subjects with ≤ 20-point decrease in PANSS Total score between Visit 1 and Visit 3 Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements Body Mass Index (BMI) must be within 18 to 40 kg/m2 Subject resides in a stable living situation in the opinion of the Investigator Subject has identified a reliable informant/ caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant needs to be physically present at the Baseline visit, but can complete the remaining study visits assessments via phone (as needed) Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. A female subject is considered to be a WOCP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).  Exclusion Criteria:  Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening)  The subject has a history of moderate to severe alcohol use disorder or substance use disorder (other than nicotine or caffeine) within the past 12 months  A screening subject with mild substance use disorder within the 12 months before Screening must be discussed and agreed upon with the Medical Monitor before being allowed into the study Subjects who test positive for cannabis at Screening may be permitted to enroll in consultation with the Medical Monitor if the subject's pattern of use is not indicative of a substance use disorder  Subject has a history of inadequate response to schizophrenia medications defined as:  Failure to minimally respond to 2 adequate courses of pharmacotherapy (a minimum of 6 weeks at an adequate dose per the label) Having received a trial of clozapine  History of symptom instability  a. > 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months  Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI versions, quetiapine, ziprasidone or lurasidone  Olanzapine is not permitted A stable dose of concomitant quetiapine up to 200 mg at bedtime for insomnia is allowed Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject or the validity of the study results Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or LFT results History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months  Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSRS as confirmed by the following:  Answers "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episode occurring within the 2 months before screening or, Answers "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before screening Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at Screening. Urine toxicology screen is positive for non-cannabis or non-benzodiazepine substances  Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (eg, lamotrigine, Depakote), lithium, tricyclic antidepressants (eg, imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (eg, lorazepam, chloral hydrate)  Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted Mirtazapine may be used as a hypnotic if started at least 8 weeks prior to Screening Pregnant, lactating, or less than 3 months postpartum If, in the opinion of the Investigator and/or Sponsor/Medical Monitor subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements Positive test for coronavirus (COVID-19) within 2 weeks or at Screening Subjects with extreme concerns relating to global pandemics, such as COVID-19, that would obscure ratings or be expected to disrupt adherence to trial procedures Unable to taper and discontinue a concomitant medication that would preclude participation in the double-blind adjunctive treatment (e.g., cannot stop anticholinergic) Subjects with prior exposure to KarXT Subjects who experienced any adverse effects due to xanomeline or trospium Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before Screening or has participated in more than 2 clinical studies in the past year Risk of violent or destructive behavior as per Investigator's judgement that would interfere with subject's participation Current involuntary hospitalization or incarceration