A Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Emraclidine
- Registration Number
- NCT05935033
- Lead Sponsor
- AbbVie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
-
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]).
-
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.
-
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
-
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 <45 beats per minute (bpm) or >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.
-
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Hepatic Function Emraclidine Participants will receive a single oral dose of 10 mg emraclidine. Moderate Hepatic Impairment Emraclidine Participants will receive a single oral dose of 10 mg emraclidine. Severe Hepatic Impairment Emraclidine Participants will receive a single oral dose of 10 milligrams (mg) emraclidine. Mild Hepatic Impairment Emraclidine Participants will receive a single oral dose of 10 mg emraclidine.
- Primary Outcome Measures
Name Time Method Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7 Area Under the Unbound Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf,u) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7 Area Under the Plasma Concentration-time Curve from Time Zero to t (AUC0-t) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7 Maximum Observed Plasma Concentration (Cmax) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7 Area Under the Unbound Plasma Concentration-time Curve from Time Zero to t (AUC0-t,u) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7 Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine Pre-dose and at multiple timepoints post-dose up to Day 7
- Secondary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Days 1 to 7 Number of Participants With Clinically Significant Changes in Vital Signs Days 1 to 7 Number of Participants With Clinically Significant Changes in Laboratory Assessments Days 1 to 7 Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results Days 1 to 7 Changes in Columbia Suicide Severity Rating Scale (C-SSRS) Score Days 1 to 7 The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk.
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) Day 1 up to Follow-up (Day 15)
Trial Locations
- Locations (3)
Miami, Florida
🇺🇸Miami, Florida, United States
Orlando, Florida
🇺🇸Orlando, Florida, United States
San Antonio, Texas
🇺🇸San Antonio, Texas, United States