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

NCT04200573 | Completed Phase 1 FDA Drug

• 1 other identifier: 0179
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Symptomatic Neurogenic Orthostatic Hypertension; nOH

Keywords

Symptomatic neurogenic orthostatic hypertension; hepatic impairment

Outcome Measures

Primary Outcomes (3)

• Plasma AUC0-t

  Estimation of Area under the concentration-time curve, from time zero to the last measured time point

  Plasma AUC0-t will be measured Day 1 to Day 15

• Plasma AUC0-inf

  Estimation of AUC from time zero extrapolated to infinity

  Plasma AUC0-inf will be measured from Day 1 to Day 15

• Plasma Cmax

  Estimation of maximum observed plasma concentration

  up to Day 21

Secondary Outcomes (2)

• Number of subjects with clinically significant vital sign abnormalities

  up to Day 21

• Number of subjects with change in C-SSRS scores

  up to Day 21

Study Arms (4)

Normal Hepatic Function

EXPERIMENTAL

Ampreloxetine Dose A single dose administration to subjects with normal hepatic function

Drug: Ampreloxetine

Mild Hepatic Function

EXPERIMENTAL

Ampreloxetine Dose A single dose administration to subjects with mild hepatic impairment

Drug: Ampreloxetine

Moderate Hepatic Function

EXPERIMENTAL

Ampreloxetine Dose A single dose administration to subjects with moderate hepatic impairment

Drug: Ampreloxetine

Severe Hepatic Function

EXPERIMENTAL

Ampreloxetine Dose A single dose administration to subjects with severe hepatic impairment

Drug: Ampreloxetine

Interventions

Ampreloxetine DRUG

The study drug will be administered orally as a single Dose A tablet

Also known as: TD-9855

Mild Hepatic Function; Moderate Hepatic Function; Normal Hepatic Function; Severe Hepatic Function

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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

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
• 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

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (2)

Theravance Biopharma Investigational Site

Miami, Florida, 33014, United States

Location

Theravance Biopharma Investigational Site

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Kanodia J, Giovinazzo H, Yates W, Bourdet DL, McRae MP, Helmke SM, Everson GT. Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine. Clin Pharmacol Ther. 2024 Jul;116(1):186-193. doi: 10.1002/cpt.3265. Epub 2024 Apr 23.

  PMID: 38654484 DERIVED

MeSH Terms

Interventions

ampreloxetine

Study Officials

• Medical Monitor

  Theravance Biopharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 16, 2019
• Study Start: January 13, 2020
• Primary Completion: August 19, 2021
• Study Completion: August 19, 2021
• Last Updated: September 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)