Thorough QT Study to Evaluate Ampreloxetine in Healthy Subjects

NCT04688632 | Completed Phase 1 FDA Drug

• 1 other identifier: 0181
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Symptomatic Neurogenic Orthostatic Hypertension; nOH

Keywords

Symptomatic neurogenic orthostatic hypertension; nOH; Thorough QT; Symptomatic nOH

Outcome Measures

Primary Outcomes (1)

• QTcF

  Change in QTcF from baseline

  Days -1, 1, 7, 8, 14 and 15

Secondary Outcomes (6)

• Cmax

  Day 1 to Day 16

• Tmax

  Day 1 to Day 16

• AUC0-24

  Day 1 to Day 16

• ECG - HR

  Days -1, 1, 7, 8, 14 and 15

• ECG - PR Interval

  Days -1, 1, 7, 8, 14 and 15

Study Arms (3)

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\>

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

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;

Drug: Ampreloxetine <Dose A>; Drug: Ampreloxetine <Dose B>; Drug: Ampreloxetine Placebo; Drug: Moxifloxacin Placebo

Interventions

Ampreloxetine <Dose A> DRUG

Ampreloxetine \<Dose A\> will be administered as 1 tablet of \<Dose A\> and 3 tablets of Ampreloxetine Placebo.

Group 2 - Treatment

Ampreloxetine <Dose B> DRUG

Ampreloxetine \<Dose B\> will be administered as 4 tablets of \<Dose A\>

Group 2 - Treatment

Ampreloxetine Placebo DRUG

Ampreloxetine Placebo will be administered as 4 tablets of placebo. The placebo tablet will match (in appearance) the ampreloxetine \<Dose A\> tablet.

Group 1a; Group 1b; Group 2 - Treatment

Moxifloxacin DRUG

Moxifloxacin will be administered orally as a single tablet.

Group 1a; Group 1b

Moxifloxacin Placebo DRUG

Moxifloxacin placebo will be administered orally as a single tablet. The placebo tablet will match (in appearance) the moxifloxacin tablet.

Group 1a; Group 1b; Group 2 - Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (1)

Theravance Biopharma Investigational Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Monitor

  Theravance Biopharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 30, 2020
• Study Start: January 18, 2021
• Primary Completion: March 13, 2021
• Study Completion: March 26, 2021
• Last Updated: April 20, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)