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Trial record 3 of 6 for:    ampreloxetine

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

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ClinicalTrials.gov Identifier: NCT04200573
Recruitment Status : Recruiting
First Posted : December 16, 2019
Last Update Posted : December 1, 2020
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

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.

Condition or disease Intervention/treatment Phase
Symptomatic Neurogenic Orthostatic Hypertension nOH Drug: Ampreloxetine Phase 1

Detailed Description:

This is a multicenter, non-randomized, open label, parallel group, single dose, 2-part study being conducted in adult subjects with mild, moderate, or severe HI (Child-Pugh Class A, B, and C), and in matching healthy subjects. The healthy matching group will be comparable to the corresponding hepatic impairment groups by matching subjects by weight (±20% of group mean), age (±10 years of group mean), and sex (equal ratios across groups).

The study will be conducted in two sequential parts:

In Part A, following a 28-day screening period, 6 subjects each with mild or moderate HI and 6 matching healthy subjects who meet eligibility criteria will be enrolled and administered a single Dose A (Day 1).

In Part B, following a 28-day screening period, 6 subjects with severe hepatic impairment will receive a single Dose A (Day 1). Furthermore, the Sponsor may choose to enroll up to 6 additional healthy subjects in Part B to ensure matching of subjects across all groups for weight, age, and sex is maintained.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics of Ampreloxetine Following a Single-dose in Subjects With Mild, Moderate, and Severe Hepatic Impairment and in Matching Healthy Subjects
Actual Study Start Date : January 13, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Normal Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with normal hepatic function
Drug: Ampreloxetine
The study drug will be administered orally as a single Dose A tablet
Other Name: TD-9855

Experimental: Mild Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with mild hepatic impairment
Drug: Ampreloxetine
The study drug will be administered orally as a single Dose A tablet
Other Name: TD-9855

Experimental: Moderate Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with moderate hepatic impairment
Drug: Ampreloxetine
The study drug will be administered orally as a single Dose A tablet
Other Name: TD-9855

Experimental: Severe Hepatic Function
Ampreloxetine Dose A single dose administration to subjects with severe hepatic impairment
Drug: Ampreloxetine
The study drug will be administered orally as a single Dose A tablet
Other Name: TD-9855




Primary Outcome Measures :
  1. Plasma AUC0-t [ Time Frame: Plasma AUC0-t will be measured Day 1 to Day 15 ]
    Estimation of Area under the concentration-time curve, from time zero to the last measured time point

  2. Plasma AUC0-inf [ Time Frame: Plasma AUC0-inf will be measured from Day 1 to Day 15 ]
    Estimation of AUC from time zero extrapolated to infinity

  3. Plasma Cmax [ Time Frame: up to Day 21 ]
    Estimation of maximum observed plasma concentration


Secondary Outcome Measures :
  1. Number of subjects with clinically significant vital sign abnormalities [ Time Frame: up to Day 21 ]
    Clinically significant abnormalities in vital signs will be listed and described

  2. Number of subjects with change in C-SSRS scores [ Time Frame: up to Day 21 ]
    Changes in Columbia suicide severity rating scale (C-SSRS) scores will be listed and described



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04200573


Contacts
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Contact: Theravance Biopharma Call Center 1-855-633-8479 medinfo@theravance.com

Locations
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United States, Florida
Theravance Biopharma Investigational Site Recruiting
Miami, Florida, United States, 33014
Theravance Biopharma Investigational Site Recruiting
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Theravance Biopharma
Investigators
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Study Director: Medical Monitor Theravance Biopharma
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Responsible Party: Theravance Biopharma
ClinicalTrials.gov Identifier: NCT04200573    
Other Study ID Numbers: 0179
First Posted: December 16, 2019    Key Record Dates
Last Update Posted: December 1, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Theravance Biopharma:
Symptomatic neurogenic orthostatic hypertension
hepatic impairment
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases