Symptomatic Neurogenic Orthostatic HypertensionPhase 1NCT04688632

Thorough QT Study to Evaluate Ampreloxetine in Healthy Subjects

A Phase 1 study testing Ampreloxetine <Dose A>, Ampreloxetine <Dose B> and Moxifloxacin in people with Symptomatic Neurogenic Orthostatic Hypertension and nOH, run by Theravance Biopharma at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A double-blind study to characterize the effect of ampreloxetine on cardiac repolarization in healthy subjects. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Symptomatic Neurogenic Orthostatic Hypertension, nOH
What is being tested?: Ampreloxetine <Dose A>, Ampreloxetine <Dose B> and Moxifloxacin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 72 participants
Where: 1 siteUnited States
Study dates: 18 Jan 2021to 26 Mar 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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subject is willing and able to give written informed consent.
Subject is a healthy, nonsmoking man or woman, 18 to 55 years of age, at screening.
Subject must be willing to abide by the following pregnancy precautions:
Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method during the study and through 30 days after the last dose of study medication.
Male subjects (with partners of childbearing potential) must use acceptable contraception during the study and through 30 days after the last dose of study medication.
Subjects must agree not to donate ova or sperm during the study and for 30 days after the last dose of study medication.

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Subject has a BMI of 18.0 to 30.0 kg/m2, inclusive, and weight of at least 55 kg at screening.
Subject has normal blood pressure (BP) and HR, measured after resting seated or supine for approximately 5 minutes. Normal BP is defined as 90 to 140 mmHg systolic and 50 to 90 mmHg diastolic. Normal HR is defined as 45 to 99 beats per minute (bpm) at screening and Day -2.
Subject is able to communicate well with the investigator and to comply with the study procedures, requirements, and restrictions.

Who cannot join

Subject has any clinically relevant abnormalities, as determined by the investigator, in the laboratory results at screening or Day -2. Except for the following clinical laboratory assessments outside the range specified:
hemoglobin <13.0 g/dL (men) or <11.5 g/dL (women),
hematocrit <38% (men) or <32% (women),
potassium <3.5 mEq/L,
magnesium <1.9 mg/dL, or
calcium <8.5 mg/dL

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Positive results at screening for human immunodeficiency virus (HIV), hepatitis A virus (HAV) antibodies (anti-HAV: both IgG and IgM positive, IgG positive in the absence of IgM positive is acceptable), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
Within 4 weeks of screening and through Day 1, subject has:
Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) (test RT-PCR positive), OR
Suspected SARS-CoV-2 infection (clinical features without documented test results) unless has a negative RT-PCR test for SARS-CoV-2 at least two weeks after resolution of symptoms and remains asymptomatic until Day 1, OR
Close contact with a person with known or suspected SARS-CoV-2 infection unless has a negative RT-PCR test for SARS-CoV-2 at least two weeks after contact and remains asymptomatic until Day 1.
Subject has a prior history of myocardial infarction, acute coronary syndrome, cerebrovascular accident, transient ischemic attack, ventricular tachycardia, atrial fibrillation, personal or known family history of congenital long QT syndrome or known family history of sudden death with unknown cause prior to the age of 50, a pacemaker or implantable cardioverter defibrillator, cardiac or cerebral stent placement or angioplasty, or clinically significant valvular heart disease.
Subject has a history of orthostatic hypotension or orthostatic tachycardia or a history of dizziness, lightheadedness or fainting, or a feeling of blacking out upon standing, secondary to autonomic failure or other chronic cardiovascular condition.
Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dosing), hematologic, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease.
Subject has a history of hypersensitivity to drugs (including moxifloxacin, related compounds, or excipients) with a clinically significant reaction or any clinically significant hypersensitivities.
Subject has any condition possibly affecting drug absorption (e.g., previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gall bladder [including cholecystectomy], or pancreas, but excluding procedures such as appendectomy and hernia repair).
Subject has participated in another clinical study of an investigational drug or medical device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to screening, or is currently participating in another study of an investigational drug or medical device.
Subject is unwilling to abstain from ingestion of caffeine or xanthine-containing products (e.g., tea, coffee, chocolate, cola, etc.) beginning 48 hours prior to admission to the CRU on Day -2 until the final PK sample has been collected.
Subject is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU on Day -2 until the final PK sample has been collected.
Subject has a history of drug abuse (in the past 3 years) or positive screen for drugs of abuse or alcohol at screening or on Day -2.
Subject has a history of alcohol consumption within 6 months prior to screening, defined as an average weekly intake of >14 units for males or >10 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 measure (25 mL) of spirits.
Subject uses or has used tobacco-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, etc.) within 6 months prior to screening or has a positive cotinine result at screening or on Day -2 and is unwilling to abstain from tobacco containing products until follow-up.
Subject has consumed grapefruit (or Seville Oranges) and/or grapefruit juice or food containing grapefruit (or Seville oranges [e.g., orange marmalade]), within 14 days prior to admission to the CRU on Day -2 and is unwilling to abstain from consuming these items until the final PK sample has been collected.
Subject has consumed other fruit juices within 48 hours prior to admission to the CRU on Day -2 and is unwilling to abstain from these items until the final PK sample has been collected.
Subject has consumed cruciferous vegetables (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard greens) or charbroiled meats within 7 days prior to admission to the CRU on Day -2 and is unwilling to abstain from these items until the final PK sample has been collected.
Subject is unwilling to abstain from any strenuous physical exercise (such as weight training, aerobics) 24 hours prior to admission to the CRU on Day -2 until the final PK sample has been collected.
Subject has acute illness (gastrointestinal illness, infection [e.g., influenza] or known inflammatory process) at screening or within 2 weeks prior to admission to the CRU on Day 2.
Subject uses any prescription drug or over-the-counter medication, including herbals or routine vitamins or minerals within 14 days or 5 half-lives (whichever is longer) prior to admission to the CRU on Day -2 or subject requires continued use of a prescription drug or over-the-counter medication during study participation.
Subject has donated blood or had blood loss of more than 400 mL or blood components within the 8 weeks prior to screening or plans to donate blood during the study.
Subject has a clinically significant abnormal screening ECG indicating a second- or third degree atrioventricular block, or one or more of the following: QRS >110 msec, QT interval corrected using Fridericia's formula (QTcF) >440 msec (men and women), PR interval >200 msec.
Subject has any significant morphological changes other than minor nonspecific T wave changes in the opinion of the investigator, including flat T waves in the inferior leads, which are interpreted by the investigator to interfere with QT analysis or to be clinically significant.
Subject has a known hypersensitivity towards medications similar to ampreloxetine or excipients contained in ampreloxetine.
Subject has previously participated in a study for ampreloxetine.
Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.
Subject, who, for any reason, is deemed by the investigator to be inappropriate for this study or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or pharmacokinetics of the investigational drug or prevent compliance with the study protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

Theravance Biopharma Investigational Site
Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled, Thorough QT Study to Evaluate the Effect of Ampreloxetine on Cardiac Repolarization in Healthy Subjects

A double-blind study to characterize the effect of ampreloxetine on cardiac repolarization in healthy subjects.

Read the detailed description

A single-center, randomized, double-blind, placebo controlled, positive controlled, multiple dose, parallel group study will be conducted in healthy male and female subjects. Subjects will be randomized to one of 3 groups:

Subjects in Group 1a (n=18) will be administered moxifloxacin placebo on Day 1, ampreloxetine placebo from Day 1 to Day 15, and moxifloxacin <Dose A> on Day 15.

Subjects in Group 1b (n=18) will be administered a single oral dose of moxifloxacin <Dose A> on Day 1, ampreloxetine placebo from Day 1 to Day 15 and moxifloxacin placebo on Day 15.

Subjects in Group 2 (n=36) will be administered moxifloxacin placebo on Day 1 and on Day 15, and ampreloxetine <Dose A> from Day 1 to Day 7, ampreloxetine <Dose B> from Day 8 to Day 14, and ampreloxetine placebo on Day 15.

Conditions: Symptomatic Neurogenic Orthostatic Hypertension, nOH
Being tested: Ampreloxetine <Dose A>, Ampreloxetine <Dose B>, Ampreloxetine Placebo, Moxifloxacin, Moxifloxacin Placebo
Keywords: Symptomatic neurogenic orthostatic hypertension, nOH, Thorough QT, Symptomatic nOH

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ampreloxetine <Dose A>Drug
Ampreloxetine <Dose A> will be administered as 1 tablet of <Dose A> and 3 tablets of Ampreloxetine Placebo.
Ampreloxetine <Dose B>Drug
Ampreloxetine <Dose B> will be administered as 4 tablets of <Dose A>
Ampreloxetine PlaceboDrug
Ampreloxetine Placebo will be administered as 4 tablets of placebo. The placebo tablet will match (in appearance) the ampreloxetine <Dose A> tablet.
MoxifloxacinDrug
Moxifloxacin will be administered orally as a single tablet.
Moxifloxacin PlaceboDrug
Moxifloxacin placebo will be administered orally as a single tablet. The placebo tablet will match (in appearance) the moxifloxacin tablet.

Study groups in NCT04688632
Study group	Role	What they receive
Group 1a	Active comparator	Day 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin <Dose A> Receives: Drug: Ampreloxetine Placebo; Drug: Moxifloxacin; Drug: Moxifloxacin Placebo
Group 1b	Active comparator	Day 1: Single dose of Moxifloxacin <Dose A>; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin Placebo Receives: Drug: Ampreloxetine Placebo; Drug: Moxifloxacin; Drug: Moxifloxacin Placebo
Group 2 - Treatment	Experimental	Day 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 7: Single daily dose of Ampreloxetine <Dose A>; Day 8 - Day 14: Single daily dose of Ampreloxetine <Dose B>; Day 15: Single dose of Moxifloxacin Placebo; Day 15: Single dose of Ampreloxetine Placebo; Receives: Drug: Ampreloxetine <Dose A>; Drug: Ampreloxetine <Dose B>; Drug: Ampreloxetine Placebo; Drug: Moxifloxacin Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

QTcF
Change in QTcF from baseline
Measured: Days -1, 1, 7, 8, 14 and 15

Secondary outcomes (6)

Cmax
Maximum observed plasma concentration (Cmax) for ampreloxetine
Measured: Day 1 to Day 16
Tmax
Time to reach maximum observed plasma concentration (Tmax) for ampreloxetine
Measured: Day 1 to Day 16
AUC0-24
Area under the concentration time curve during 0-24 hours (AUC0-24) for ampreloxetine
Measured: Day 1 to Day 16
ECG - HR
Change-from-baseline in Electrocardiogram (ECG) - Heart Rate (HR)
Measured: Days -1, 1, 7, 8, 14 and 15
ECG - PR Interval
Change-from-baseline in Electrocardiogram (ECG) - PR Interval
Measured: Days -1, 1, 7, 8, 14 and 15
ECG - QRS Interval
Change-from-baseline in Electrocardiogram (ECG) - QRS Interval
Measured: Days -1, 1, 7, 8, 14 and 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jan 202126 Mar 2021

First posted30 Dec 2020
Study start18 Jan 2021
Primary completion13 Mar 2021
Study completion26 Mar 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
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: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04688632
Sponsor's protocol ID: 0181
Status last verified: Apr 2021
First submitted: 23 Dec 2020
Last updated: 20 Apr 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.

Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled, Thorough QT Study to Evaluate the Effect of Ampreloxetine on Cardiac Repolarization in Healthy Subjects
ClinicalTrials.gov ID: NCT04688632
Acronym / sponsor ID: 0181
Conditions: Symptomatic Neurogenic Orthostatic Hypertension, nOH
Keywords: Symptomatic neurogenic orthostatic hypertension, nOH, Thorough QT, Symptomatic nOH
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: Theravance BiopharmaIndustry (pharma, biotech, devices)
Study start: 18 Jan 2021 (actual)
Primary completion: 13 Mar 2021 (actual)
Study completion: 26 Mar 2021 (actual)
First posted: 30 Dec 2020 (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.

A double-blind study to characterize the effect of ampreloxetine on cardiac repolarization in healthy subjects.

Detailed description

Subjects in Group 1a (n=18) will be administered moxifloxacin placebo on Day 1, ampreloxetine placebo from Day 1 to Day 15, and moxifloxacin <Dose A> on Day 15.

Subjects in Group 1b (n=18) will be administered a single oral dose of moxifloxacin <Dose A> on Day 1, ampreloxetine placebo from Day 1 to Day 15 and moxifloxacin placebo on Day 15.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Group 1a	Active comparator	Drug: Ampreloxetine Placebo, Drug: Moxifloxacin, Drug: Moxifloxacin PlaceboDay 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin <Dose A>
Group 1b	Active comparator	Drug: Ampreloxetine Placebo, Drug: Moxifloxacin, Drug: Moxifloxacin PlaceboDay 1: Single dose of Moxifloxacin <Dose A>; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin Placebo
Group 2 - Treatment	Experimental	Drug: Ampreloxetine <Dose A>, Drug: Ampreloxetine <Dose B>, Drug: Ampreloxetine Placebo, Drug: Moxifloxacin PlaceboDay 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 7: Single daily dose of Ampreloxetine <Dose A>; Day 8 - Day 14: Single daily dose of Ampreloxetine <Dose B>; Day 15: Single dose of Moxifloxacin Placebo; Day 15: Single dose of Ampreloxetine Placebo;

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Subject is willing and able to give written informed consent.
Subject is a healthy, nonsmoking man or woman, 18 to 55 years of age, at screening.
Subject must be willing to abide by the following pregnancy precautions:
Subject has a BMI of 18.0 to 30.0 kg/m2, inclusive, and weight of at least 55 kg at screening.
Subject has normal blood pressure (BP) and HR, measured after resting seated or supine for approximately 5 minutes. Normal BP is defined as 90 to 140 mmHg systolic and 50 to 90 mmHg diastolic. Normal HR is defined as 45 to 99 beats per minute (bpm) at screening and Day -2.

Key exclusion criteria (35 listed)

Subject has any clinically relevant abnormalities, as determined by the investigator, in the laboratory results at screening or Day -2. Except for the following clinical laboratory assessments outside the range specified:
Positive results at screening for human immunodeficiency virus (HIV), hepatitis A virus (HAV) antibodies (anti-HAV: both IgG and IgM positive, IgG positive in the absence of IgM positive is acceptable), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
Within 4 weeks of screening and through Day 1, subject has:
Subject has a prior history of myocardial infarction, acute coronary syndrome, cerebrovascular accident, transient ischemic attack, ventricular tachycardia, atrial fibrillation, personal or known family history of congenital long QT syndrome or known family history of sudden death with unknown cause prior to the age of 50, a pacemaker or implantable cardioverter defibrillator, cardiac or cerebral stent placement or angioplasty, or clinically significant valvular heart disease.
Subject has a history of orthostatic hypotension or orthostatic tachycardia or a history of dizziness, lightheadedness or fainting, or a feeling of blacking out upon standing, secondary to autonomic failure or other chronic cardiovascular condition.

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
Ampreloxetine <Dose A>Ampreloxetine <Dose A> will be administered as 1 tablet of <Dose A> and 3 tablets of Ampreloxetine Placebo.	Drug	Group 2 - Treatment
Ampreloxetine <Dose B>Ampreloxetine <Dose B> will be administered as 4 tablets of <Dose A>	Drug	Group 2 - Treatment
Ampreloxetine PlaceboAmpreloxetine Placebo will be administered as 4 tablets of placebo. The placebo tablet will match (in appearance) the ampreloxetine <Dose A> tablet.	Drug	Group 1a, Group 1b, Group 2 - Treatment
MoxifloxacinMoxifloxacin will be administered orally as a single tablet.	Drug	Group 1a, Group 1b
Moxifloxacin PlaceboMoxifloxacin placebo will be administered orally as a single tablet. The placebo tablet will match (in appearance) the moxifloxacin tablet.	Drug	Group 1a, Group 1b, Group 2 - Treatment

Primary outcome

QTcF
Time frame: Days -1, 1, 7, 8, 14 and 15
Change in QTcF from baseline

6 secondary outcomes

Cmax
Time frame: Day 1 to Day 16
Tmax
Time frame: Day 1 to Day 16
AUC0-24
Time frame: Day 1 to Day 16
ECG - HR
Time frame: Days -1, 1, 7, 8, 14 and 15
ECG - PR Interval
Time frame: Days -1, 1, 7, 8, 14 and 15
ECG - QRS Interval
Time frame: Days -1, 1, 7, 8, 14 and 15

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 20 Apr 2021.
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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 35 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 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

QTcF (time frame: Days -1, 1, 7, 8, 14 and 15). 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 NCT04688632.

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 20 Apr 2021.