Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects

This is an interventional treatment trial for Liver Failure focused on measuring hepatic, hepatic impairment, lofexidine Read More

Inclusion Criteria:

Site will evaluate each subject for criteria in detail, which will include:

1. Between ages of 18 to 65 years at enrollment with a BMI between 19 and 38 kg/m2, inclusive.

2. Subject is eligible to enter the study if:

   • Matched control subject: normal hepatic function and free from other clinically significant illnesses or disease, and medical history, physical examination, laboratory results, and other tests consistent with health, as determined by the Investigator.
   • Subject with mild hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 5-6 Points (Stage A) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
   • Subject with moderate hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 7 9 Points (Stage B) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
   • Subject with severe hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 10-15 Points (Stage C) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.

Exclusion Criteria:

Site will evaluate each subject for criteria in detail, which will include:

1. The matched control subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease or the hepatically-impaired subject has a history of clinically significant disease including cardiovascular, GI, renal, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.

2. Abnormal cardiovascular exam at Screening, including any of the following:

   • clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF (Fridericia's correction) interval >450 msec for males and >470 msec for females).
   • heart rate <45 bpm or symptomatic bradycardia;
   • systolic blood pressure <90 mmHg or symptomatic hypotension;
   • blood pressure >160/100 mmHg; or
   • prior history of myocardial infarction.

3. Subjects with hepatic impairment will not be eligible to participate in the study if any of the following exclusion criteria also apply:

   • Significant bleeding diathesis or esophageal bleeding within the last 8 weeks.
   • Evidence of hepatic function deterioration within the last 4 weeks as indicated by liver transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase or a ≥50% worsening of serum bilirubin or prothrombin time.
   • History of surgical portosystemic shunt.
   • Prothrombin time >18 seconds.