Drug-Interaction Study to Evaluate the Effect of Rifampin, a Potent CYP3A4 Inducer, on the Systemic Exposure of Pacritinib in Healthy Subjects

This was a single-center, open-label, one-way crossover, drug-interaction study. On Day 1,
subjects received a single oral 400-mg dose of pacritinib. Following a 7-day washout period,
600-mg oral doses of rifampin were administered once daily (QD) on Days 8 through 17. It was
anticipated that steady-state concentrations of rifampin would be achieved by Day 17. On Day
17, a single oral 400-mg dose of pacritinib was co-administered with the final 600-mg dose
of rifampin.

Inclusion Criteria:

Subjects who meet the following criteria may be included in the study:

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 sign measurements;

4. 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 and in consultation with the
Sponsor;

5. negative test for selected drugs of abuse (including alcohol) at Screening and at
Check-in (Day -1);

6. negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and hepatitis
C virus antibody [anti-HCV]) and negative HIV antibody screens;

7. 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 Form (ICF) or 10 days prior to Check-in (Day -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 ICF or 10 days
prior to Check-in (Day -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). Females not of childbearing potential must have had continuous amenorrhea for at
least 12 months or surgically sterile (eg, tubal ligation, hysterectomy) for at least
90 days prior to Screening;

8. males will either be surgically sterile (ie, vasectomy, documented in the medical
record by a physician) or agree to use, from Check-in (Day -1) until 90 days
following Study Completion/Early Termination (ET), one 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) until 90 days following Study Completion/ET;

9. able to comprehend and willing to sign an ICF

Exclusion Criteria:

The following will exclude potential subjects from the study:

1. 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; appendectomy and cholecystectomy are not considered
to be clinically significant procedures);

2. abnormalities in liver function tests (any/all of alanine aminotransferase, aspartate
aminotransferase, or alkaline phosphatase > upper limit of normal [ULN];
gamma-glutamyl transferase > ULN; or total bilirubin

> ULN) or kidney function tests (serum creatinine > ULN); laboratory values may be
confirmed by repeat;

3. 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;

4. history of significant hypersensitivity, intolerance, or allergy to any drug
compound, food, or other substance, including rifampin, unless approved by the
Investigator in consultation with the Sponsor;

5. history of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs except that appendectomy and
hernia repair will be allowed;

6. history of Gilbert's Syndrome;

7. history or presence of an abnormal ECG, which, in the Investigator's opinion, is
clinically significant; QT corrected for heart rate using Fridericia's formula (QTcF)
>450 msec; or 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);

8. history of alcoholism or drug addiction within 1 year prior to Check-in (Day -1);

9. use of tobacco- or nicotine-containing products within 6 months prior to Check-in
(Day -1) and during the entire study;

10. receipt of blood products within 2 months prior to Check-in (Day -1);

11. participation in any other investigational drug trial in which receipt of an
investigational study drug occurred within 5 half-lives or 30 days prior to Check-in
(Day -1), whichever is longer;

12. donation of blood from 30 days prior to Screening through Study Completion/ET,
inclusive, or of plasma from 2 weeks prior to Screening through Study Completion/ET,
inclusive;

13. use of any prescription medications and/or products within 14 days prior to Check-in
(Day -1) and during the entire study, unless deemed acceptable by the Investigator in
consultation with the Sponsor;

14. use of oral, implantable, injectable, or transdermal hormonal contraceptives within
10 days prior to Check-in (Day -1) or from the time of signing the ICF (females only)
until 14 days after the final dose administration;

15. use of any over-the-counter, non-prescription preparations (including vitamins,
minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior
to Check-in (Day -1) and during the entire study, unless deemed acceptable by the
Investigator;

16. consumption of alcohol- or caffeine-containing foods and beverages for 72 hours prior
to Check-in (Day -1) and during the entire study;

17. consumption of grapefruit-containing foods and beverages or other CYP3A4 inhibitors
or inducers for 72 hours prior to Check-in (Day -1) and during the entire study;

18. participation in strenuous exercise for 48 hours prior to Check-in (Day -1) and
during the period of confinement at the CRU; subjects 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);

19. poor peripheral venous access;

20. 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