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

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: US WorldMeds LLC
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Clonidine; Lofexidine

Criteria

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.