| Eligibility |
Inclusion Criteria:
1. males or females, between 18 and 55 years of age, inclusive;
2. BMI between 18.5 and 32.0 kg/m2, inclusive;
3. in good health, determined by no clinically significant findings from medical history,
physical examination, and vital signs;
4. normal 12-lead ECG or ECG findings (including RR, PR, and QT intervals; QT interval
corrected using Fridericia's formula [QTcF]; QRS duration; and ventricular heart rate)
deemed not clinically significant;
5. clinical laboratory evaluations (including clinical chemistry panel [fasted at least
10 hours], CBC, and UA) within the reference range for the test laboratory, unless
deemed not clinically significant by the Investigator in consultation with the
Sponsor;
6. negative test for selected drugs of abuse (including alcohol) at Screening and at
Check-in (Day -1 of Period 1);
7. negative hepatitis panel (including HBsAg and anti-HCV) and negative HIV antibody
screens;
8. females of childbearing potential must be non-pregnant and non-lactating, and agree to
use one of the following forms of contraception from the time of signing the informed
consent or 10 days prior to Check-in (Day -1) of Period 1 until 30 days after the
final dose administration: non-hormonal intrauterine device (IUD) with spermicide;
female condom with spermicide; contraceptive sponge with spermicide; intravaginal
system (eg, NuvaRing®); diaphragm with spermicide; cervical cap with spermicide; male
sexual partner who agrees to use a male condom with spermicide; sterile sexual
partner; or abstinence. Oral, implantable, transdermal, or injectable hormonal
contraceptives may not be used from the time of signing the informed consent or 10
days prior to Check-in (Day -1) of Period 1 until 14 days after the final dose
administration. For all females, the pregnancy test result must be negative at
Screening and Check-in (Day -1) of Period 1. Females not of childbearing potential
must be postmenopausal for at least 1 year or surgically sterile (eg, tubal ligation,
hysterectomy) for at least 90 days;
9. males will be surgically sterile (ie, vasectomy, documented in the medical record by a
physician) or agree to use, from Check-in (Day -1) of Period 1 until 90 days following
Study Completion/ET, 1 of the following approved methods of contraception: male condom
with spermicide; sterile sexual partner; or use by female sexual partner of an IUD
with spermicide, a female condom with spermicide, a contraceptive sponge with
spermicide, an intravaginal system, a diaphragm with spermicide, a cervical cap with
spermicide, or oral, implantable, transdermal, or injectable contraceptives. Subjects
must agree to refrain from sperm donation from Check-in (Day -1) of Period 1 until 90
days following Study Completion/ET;
10. able to comprehend and willing to sign an Informed Consent Form (ICF).
Exclusion Criteria:
1. prior ingestion of pacritinib;
2. history or clinical manifestation of clinically significant cardiovascular, pulmonary,
hepatic (eg, hepatitis), renal, hematologic, gastrointestinal (eg, celiac disease,
peptic ulcer, gastroesophageal reflux, inflammatory bowel disease), metabolic,
allergic, dermatological, neurological, or psychiatric disorder (as determined by the
Investigator in consultation with the Sponsor; appendectomy and cholecystectomy are
not considered to be clinically significant events);
3. significant abnormalities in liver function tests (alanine aminotransferase, aspartate
aminotransferase, or alkaline phosphatase >1.5 × upper limit of normal [ULN];
gamma-glutamyl transferase >2 × ULN; or total bilirubin >1.3 × ULN) or kidney function
tests (serum creatinine > ULN) that are considered clinically significant by the
Investigator, in consultation with the Sponsor;
4. history of malignancy, except the following: cancers determined to be cured or in
remission for =5 years, curatively resected basal cell or squamous cell skin cancers,
cervical cancer in situ, or resected colonic polyps;
5. history of significant hypersensitivity, intolerance, or allergy to any drug compound,
food, or other substance, unless approved by the Investigator in consultation with the
Sponsor;
6. history of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs except that appendectomy,
cholecystectomy, and hernia repair will be allowed;
7. history of Gilbert's Syndrome;
8. history or presence of ECG QTcF >450 msec, factors that increase risk for QTc interval
prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L
that is persistent and refractory to correction], or family history of long QT
interval syndrome);
9. history of alcoholism or drug addiction within 1 year prior to Check-in (Day -1) of
Period 1;
10. use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day
-1) of Period 1 and during the entire study;
11. consumption of alcohol- or caffeine-containing foods and beverages for 72 hours prior
to Screening and during the entire study;
12. consumption of grapefruit-containing foods and beverages or other CYP3A4 inhibitors or
inducers for 72 hours prior to Screening and during the entire study. A list of CYP3A4
inhibitors and inducers is provided in;
13. subjects will refrain from strenuous exercise from 48 hours prior to Check-in (Day -1)
of Period 1 and during the period of confinement at the CRU and will otherwise
maintain their normal level of physical activity throughout the entire study (ie, will
not begin a new exercise program nor participate in any unusually strenuous physical
exertion);
14. participation in any other investigational study drug trial in which receipt of an
investigational study drug occurred within 5 half-lives or 30 days prior to Check-in
(Day -1) of Period 1, whichever is longer, and during the entire study;
15. female subjects who are unable to refrain from the use of oral, implantable,
injectable, or transdermal hormonal contraceptives within 10 days prior to Check-in
(Day -1) of Period 1 or from the time of signing the informed consent until 14 days
after the final dose administration;
16. use of any prescription medications and/or products within 14 days prior to Check-in
(Day -1) of Period 1 and during the entire study, unless deemed acceptable by the
Investigator in consultation with the Sponsor;
17. use of any over-the-counter, non-prescription medications (including vitamins,
minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior
to Check-in (Day -1) of Period 1 and during the entire study, unless deemed acceptable
by the Investigator in consultation with the Sponsor;
18. poor peripheral venous access;
19. donation of blood from 30 days prior to Screening through Study Completion/ET,
inclusive, or plasma from 2 weeks prior to Screening through Study Completion/ET,
inclusive;
20. receipt of blood products within 2 months prior to Check-in (Day -1) of Period 1;
21. any acute or chronic condition that, in the opinion of the Investigator, would limit
the subject's ability to complete and/or participate in this clinical study.
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