a study to evaluate the effect of hepatic impairment on the pharmacokinetics of emraclidine

Conditions: Hepatic Impairment

Summary: the primary purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (pk) of emraclidine following administration of a single oral dose in participants with mild, moderate, and severe hepatic impairment relative to matched participants with normal hepatic function.


Eligibility criteria:
key inclusion criteria: 1. all participants - male and female participants, body mass index of ≥18.0 to 42.0 kilograms per meter square (kg/m\^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds \[lbs\]). 2. additional inclusion criteria for participants with normal hepatic function * participants who are healthy, having no clinically relevant abnormalities. have normal hepatic function. * alanine aminotransferase (alt), aspartate aminotransferase (ast), alkaline phosphatase (alp), bilirubin and prothrombin time ≤ upper limit of normal (uln) and albumin ≥ lower limit of normal (lln) and ≤ uln. participants with a history of gilbert syndrome are eligible provided direct bilirubin fraction is \<20% of total bilirubin, and hemoglobin, and reticulocyte counts are all ≤ uln. 3. additional inclusion criteria for participants with hepatic impairment - participants with stable hepatic impairment that meets the criteria for class a, class b, or class c of the modified child-pugh classification. stable hepatic disease defined as no clinically significant change in disease status in the last 28 days prior to the screening visit. key exclusion criteria: 1. for all participants * any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, and cholecystectomy. * receipt of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) vaccination or booster within 7 days of planned dosing. * have recently been diagnosed with symptomatic coronavirus disease 2019 (covid-19) or test positive for sars-cov-2 within 15 days prior to signing the informed consent form (icf). * positive drug screen or a positive test for alcohol at screening or baseline (check-in/day -1) visits. * use of prohibited medications prior to randomization or likely to require prohibited concomitant therapy during the trial. * current use of tobacco or nicotine-containing products (cigarettes, cigars, chewing tobacco, snuff, e-cigarettes, etc). note: light smokers (\<5 cigarettes/day or equivalent) are allowed provided they abstain from the use of tobacco- or nicotine-containing products for at least 2 hours prior to pk assessments. * known allergy or hypersensitivity to the investigational medicinal product (imp), closely related compounds, or any of their specified ingredients. * has received imp in a clinical trial of emraclidine within 12 months of signing the icf. * participants with a 12-lead ecg demonstrating any of the following at the screening visit and at check-in (day -1): * qt interval corrected for heart rate using fridericia's formula (qtcf) interval \>470 milliseconds (ms) * qrs interval \>120 ms (unless right bundle branch block) * pr interval \>200 ms * left ventricular hypertrophy (lvh) with st depressions and/or t wave inversions in leads with relatively tall r waves (ie, lvh with associated st-t wave abnormalities) * type 2 second-degree or third-degree atrioventricular block * heart rate \ 100 bpm * abnormal ecg changes (such as clinically significant st depression or elevation or t wave inversion). * abnormal heart rhythm (such as atrial fibrillation and atrial flutter) * blood pressure measurements demonstrating any of the following at the screening visit and/or at check-in (day -1): * supine systolic blood pressure ≥140 millimeters of mercury (mmhg) and/or diastolic blood pressure ≥90 mmhg * standing systolic and/or diastolic blood pressure ≥140 mmhg and/or diastolic blood pressure ≥90 mmhg * orthostatic hypotension, defined as a decrease of ≥20 mmhg in systolic blood pressure and/or ≥10 mmhg in diastolic blood pressure after at least 2 minutes of standing compared with the average of the resting supine blood pressure measurements. 2. additional exclusion criteria for participants with hepatic impairment * estimated glomerular filtration rate (egfr) \<60 ml/min/1.73m\^2 based on the chronic kidney disease-epidemiology collaboration (ckd-epi) equation at screening or check-in (day -1) visits * acute hepatitis * grade ≥2 hepatic encephalopathy * participants who have received an organ transplant or are currently waiting for an organ transplant and are listed on the national transplant list. * primary biliary cholangitis or primary sclerosing cholangitis * alt or ast \>5 × uln or alkaline phosphatase \>2 × uln. participants with a history of gilbert syndrome are eligible provided direct bilirubin fraction is \<20% of total bilirubin.