Eligibility Details:
Inclusion Criteria:
1. Signed the informed consent form (ICF) approved by an institutional review board
(IRB).
2. Determined to have genotype TT, AA, or AT.
3. Weighs at least 50 kg and not more than 100 kg.
4. If female, must be surgically sterile for at least 6 months prior to screening,
post-menopausal for at least 1 year, using adequate contraception, have a vasectomized
partner or abstinent.
5. Subject is in good physical health as determined by the investigator, based on
physical examination, medical history, 12-lead ECG, vital signs, and clinical
laboratory tests.
6. Subject is willing and able to comply with all aspects of the protocol, including the
diet and medication restrictions.
Exclusion Criteria:
1. If female, breastfeeding or pregnant.
2. Use of any prescription or over-the-counter drugs.
3. Clinical laboratory test results outside laboratory normal range that are determined
by the investigator to be clinically significant.
4. Creatinine clearance <90 mL/min (estimated by Cockcroft-Gault formula).
5. Pulse rate ≤50 or ≥100 bpm, systolic blood pressure ≤90 or ≥140 mmHg, diastolic blood
pressure ≤60 or ≥90 mmHg or a history of hypertension, recurrent hypotensive events,
or known orthostatic hypotension.
6. ECG abnormalities (PR >200 msec; QRS complex >120 msec; QT interval corrected for
heart rate using Fridericia's formula [QTcF] interval >450 msec if male and >470 msec
if female, or history of clinically significant ECG abnormalities (such as cardiac
arrhythmia, familial long QT syndrome, or previous torsade de pointes).
7. History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone
secretion, or any other disorder associated with fluid or sodium imbalance.
8. History or evidence of any clinically significant surgical or medical condition (eg,
cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic,
metabolic, urologic, pulmonary, neurologic, psychiatric, dermatologic, renal, and/or
another major disease or malignancy) that would be anticipated, in the opinion of the
investigator, to compromise subject safety or PK evaluation.
9. Known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.
10. Clinically significant history of allergic conditions (including drug allergies,
asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic
seasonal allergies), as judged by the investigator.
11. History of or current infection with hepatitis B virus, hepatitis C virus, or human
immunodeficiency virus.
12. Use of tobacco- or nicotine-containing products in the 6 months prior or intent to
smoke during the study. Smoking status will be confirmed by negative urine cotinine
test.
13. Consumption of more than 21 units (males) or more than 14 units (females) of alcohol
per week (1 unit = 10 g pure alcohol or 250 mL of beer [5%], 35 mL of spirits [35%],
or 100 mL of wine [12%]). Alcohol use is prohibited from 72 hours prior to admission
on Day -2 until discharge from clinical unit.
14. History of chronic drug or alcohol abuse in the last 4 years. Lack of abuse will be
confirmed by urine screens for alcohol and drugs of abuse (amphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine metabolites, methamphetamines,
methylenedioxymethamphetamine, and opiates [including heroin, codeine, and
oxycodone]).
15. Participation in a clinical trial of an investigational drug within the 30 days prior
to admission on Day -2.
16. Significant blood loss or donation (≥500 mL within the 30 days prior to admission on
Day -2).
17. Is an employee or the close relative of an employee of the sponsor or clinical unit.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
