| Eligibility |
Inclusion Criteria:
1. Subject is willing and able to give written informed consent.
2. Subject is a healthy, nonsmoking man or woman, 18 to 55 years of age, at screening.
3. 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.
4. Subject has a BMI of 18.0 to 30.0 kg/m2, inclusive, and weight of at least 55 kg at
screening.
5. 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.
6. Subject is able to communicate well with the investigator and to comply with the study
procedures, requirements, and restrictions.
Exclusion Criteria:
1. 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
2. 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.
3. Within 4 weeks of screening and through Day 1, subject has:
1. Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
(COVID-19) (test RT-PCR positive), OR
2. 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
3. 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.
4. 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.
5. 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.
6. 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.
7. Subject has a history of hypersensitivity to drugs (including moxifloxacin, related
compounds, or excipients) with a clinically significant reaction or any clinically
significant hypersensitivities.
8. 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).
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. Subject has a known hypersensitivity towards medications similar to ampreloxetine or
excipients contained in ampreloxetine.
25. Subject has previously participated in a study for ampreloxetine.
26. 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.
27. 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.
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