USWM-LX1-1007

About this trial

Last updated 7 years ago

Study ID

USWM-LX1-1007

Status

Completed

Type

Interventional

Phase

Phase 1

Placebo

Accepting

18 to 65 Years

All

Trial Timing

Ended 11 years ago

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.

Inclusion Criteria

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

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.

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