Effect of Hepatic Impairment on the Pharmacokinetics of a Single Dose of TD-9855

• Status: Completed
• Trial end date: 2021-08-19
• Target enrollment: 0
• Participant gender: All

Summary

An open-label study to characterize the effects of mild, moderate, and severe Hepatic Impairment (HI) on the pharmacokinetics (PK) of ampreloxetine following a single oral dose in comparison with healthy volunteers with normal hepatic function.

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

Details

• Lead Sponsor: Theravance Biopharma

Criteria

Inclusion Criteria:

All Subjects:

• has a body mass index (BMI) of 19 to 40 kg/m2, inclusive, and weight of at least 55 kg.

• clinical labs within normal ranges

• creatinine clearance of >70 mL/min

• women must be non-pregnant and non-lactating, male and females must agree to highly effective methods of contraception

• additional criteria apply

Subjects with Impaired Hepatic Function additional criteria:

• Subject has mild (Child-Pugh Class A [5 to 6 points]), moderate (Child-Pugh Class B [7 to 9 points]), or severe (Child-Pugh Class C [10-15 points]) liver disease

• has stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days

• must be on a stable dose of medication and/or treatment regimen at least 30 days before dosing

• Additional inclusion criteria apply

Exclusion Criteria:

Subjects with normal hepatic function:

• history of reactions or hypersensitivity to ampreloxetine or known intolerance to other norepinephrine reuptake inhibitors (NRI) or serotonin norepinephrine reuptake inhibitors (SNRI).

• personal or family history of congenital long QT syndrome

• history of untreated closed angle glaucoma

• history of orthostatic hypotension or orthostatic tachycardia or a history of dizziness, lightheadedness or fainting, or a feeling of blacking out upon standing

• has used nephrotoxic or hepatotoxic medications 30 days before Day-2

• routinely uses more than 2 grams of acetaminophen daily

• has used tobacco-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, e cigarettes, vaporizers) within 3 months before Screening or has a positive cotinine result at Screening or Day -2

• used any CYP1A2 inhibitor or inducer within 7 days or 5 half lives, whichever is longer, prior to ampreloxetine dosing or requires concomitant use

• has used monoamine oxidase inhibitors (MAO-I) within 7 days or 5 half lives, whichever is longer, prior to ampreloxetine dosing or requires concomitant use

• additional exclusion criteria apply

Subjects with impaired hepatic function additional criteria:

• has severe ascites that could potentially interfere with respiratory function

• current severe hepatic encephalopathy

• history of liver transplantation, hepatocellular carcinoma, or acute liver disease

• has biliary liver cirrhosis

• has uncontrolled hypertension (SBP >180 mm Hg and DBP (Diastolic blood pressure) >110 mm Hg)

• has an abnormal ECG at Screening or Day -2, including QTcF (Fridericia's corrected QT Interval) >470 msec

• additional exclusion criteria apply