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

Completed · Phase 1

Conditions studied: Symptomatic Neurogenic Orthostatic Hypertension, nOH

In brief

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.

Key facts

Study ID: NCT04200573
Run by: Theravance Biopharma
People needed: 31
Starts: 2020-01-13
Expected to finish: 2021-08-19
Last updated by the study team: 2021-09-08

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

Theravance Biopharma Investigational Site — Miami, Florida, United States
Theravance Biopharma Investigational Site — Orlando, Florida, United States

Full record on ClinicalTrials.gov

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