Symptomatic Neurogenic Orthostatic HypertensionPhase 1NCT04200573
Effect of Hepatic Impairment on the Pharmacokinetics of a Single Dose of TD-9855
A Phase 1 study testing Ampreloxetine in people with Symptomatic Neurogenic Orthostatic Hypertension and nOH, run by Theravance Biopharma at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Symptomatic Neurogenic Orthostatic Hypertension, nOH
- What is being tested?
- Ampreloxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Jan 2020to 19 Aug 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Theravance Biopharma Investigational Site
Miami, Florida, 33014
Theravance Biopharma Investigational Site
Orlando, Florida, 32809
About this study
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
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.
Read the 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.
- Being tested
- Ampreloxetine
- Keywords
- Symptomatic neurogenic orthostatic hypertension, hepatic impairment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmpreloxetineDrug
Also called TD-9855
The study drug will be administered orally as a single Dose A tablet
| Study group | Role | What they receive |
|---|---|---|
| Normal Hepatic Function | Experimental | Ampreloxetine Dose A single dose administration to subjects with normal hepatic function Receives: Drug: Ampreloxetine |
| Mild Hepatic Function | Experimental | Ampreloxetine Dose A single dose administration to subjects with mild hepatic impairment Receives: Drug: Ampreloxetine |
| Moderate Hepatic Function | Experimental | Ampreloxetine Dose A single dose administration to subjects with moderate hepatic impairment Receives: Drug: Ampreloxetine |
| Severe Hepatic Function | Experimental | Ampreloxetine Dose A single dose administration to subjects with severe hepatic impairment Receives: Drug: Ampreloxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma AUC0-t
Estimation of Area under the concentration-time curve, from time zero to the last measured time point
Measured: Plasma AUC0-t will be measured Day 1 to Day 15
Plasma AUC0-inf
Estimation of AUC from time zero extrapolated to infinity
Measured: Plasma AUC0-inf will be measured from Day 1 to Day 15
Plasma Cmax
Estimation of maximum observed plasma concentration
Measured: up to Day 21
Secondary outcomes (2)
Number of subjects with clinically significant vital sign abnormalities
Clinically significant abnormalities in vital signs will be listed and described
Measured: up to Day 21
Number of subjects with change in C-SSRS scores
Changes in Columbia suicide severity rating scale (C-SSRS) scores will be listed and described
Measured: up to Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start13 Jan 2020
- Primary completion19 Aug 2021
- Study completion19 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Symptomatic Neurogenic Orthostatic HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theravance Biopharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Theravance Biopharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200573
- Sponsor's protocol ID
- 0179
- Status last verified
- Sep 2021
- First submitted
- 13 Dec 2019
- Last updated
- 8 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Publications
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.
PubMed 38654484
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04200573
- Acronym / sponsor ID
- 0179
- Keywords
- Symptomatic neurogenic orthostatic hypertension, hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Theravance BiopharmaIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 19 Aug 2021 (actual)
- Study completion
- 19 Aug 2021 (actual)
- First posted
- 16 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal Hepatic Function | Experimental | Drug: AmpreloxetineAmpreloxetine Dose A single dose administration to subjects with normal hepatic function |
| Mild Hepatic Function | Experimental | Drug: AmpreloxetineAmpreloxetine Dose A single dose administration to subjects with mild hepatic impairment |
| Moderate Hepatic Function | Experimental | Drug: AmpreloxetineAmpreloxetine Dose A single dose administration to subjects with moderate hepatic impairment |
| Severe Hepatic Function | Experimental | Drug: AmpreloxetineAmpreloxetine Dose A single dose administration to subjects with severe hepatic impairment |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmpreloxetineAlso: TD-9855The study drug will be administered orally as a single Dose A tablet | Drug | Mild Hepatic Function, Moderate Hepatic Function, Normal Hepatic Function, Severe Hepatic Function |
Primary outcome
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
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
Plasma Cmax
Time frame: up to Day 21
Estimation of maximum observed plasma concentration
2 secondary outcomes
Number of subjects with clinically significant vital sign abnormalities
Time frame: up to Day 21
Number of subjects with change in C-SSRS scores
Time frame: up to Day 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Derived from this study: PubMed 38654484Kanodia 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.
- Individual participant dataSharing planned: No. Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Theravance Biopharma
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ampreloxetine in people with Symptomatic Neurogenic Orthostatic Hypertension and nOH, run by Theravance Biopharma at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma AUC0-t (time frame: Plasma AUC0-t will be measured Day 1 to Day 15). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04200573, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2021.