Determine Pacritinib Pharmacokinetics in Impaired Hepatic Patients and Healthy Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02765724
• Date of registration: 03/05/2016
• Prospective Registration: No
• Primary sponsor: CTI BioPharma
• Public title: Determine Pacritinib Pharmacokinetics in Impaired Hepatic Patients and Healthy Subjects
• Scientific title: A Phase 1 Open Label, Single Dose, Parallel-Group Study to Determine the Pharmacokinetics of Pacritinib in Patients With Impaired Hepatic Function in Comparison With Healthy Subjects
• Date of first enrolment: January 2015
• Target sample size: 28
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02765724
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Germany, Moldova, Republic of

Contacts

• Name: James Dean, MD, PhD
• Affiliation: CTI BioPharma

Key inclusion & exclusion criteria

Inclusion Criteria:

All Study Participants

1. Male and/or female from 18-85 years of age, inclusive

2. Must be in sufficiently good health to tolerate the study treatment and procedures and
be evaluable for possible effects of hepatic dysfunction on pacritinib PK without
significant confounding issues, in the opinion of the investigator in consultation
with the Sponsor

3. Must be using a medically-approved birth control method

- Females must be non-pregnant and non-lactating, and females not of childbearing
potential must be postmenopausal for at least 1 year or surgically sterile (e.g.,
tubal ligation, hysterectomy) for at least 90 days, or agree to use, from the
time of signing the informed consent or 10 days prior to Check-in (Day -1) until
30 days after Study Completion (Day 8)/Early Termination, one of the following
forms of contraception: non-hormonal intrauterine device (IUD) with spermicide;
female condom with spermicide; contraceptive sponge with spermicide; intravaginal
system (e.g., 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 contraceptives may not be used from the time of signing the informed
consent 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)

- Males will be sterile, or completely abstain from sexual intercourse, or agree to
use, from Check-in (Day -1) until 90 days following Study Completion/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.
Study participants will refrain from sperm donation from Check-in (Day -1) until
90 days following Study Completion (Day 8)

4. BMI between 18-40 kg/m2 (inclusive) at Screening

5. Vital signs (after 3 minutes seated position rest then measured in the seated
position) within the following ranges, inclusive, unless deemed not clinically
significant by the Investigator, as approved by the Sponsor:

- oral body temperature between 35.0-37.5 °C

- systolic blood pressure, 90-160 mm Hg

- diastolic blood pressure, 50-100 mm Hg

- pulse rate, 50-100 bpm

Blood pressure and pulse will be taken again in a standing position. After 3 minutes
standing, there shall be no more than a 20 mm Hg drop in systolic blood pressure
associated with symptomatic postural hypotension

6. Negative test for selected drugs of abuse (including alcohol) at Screening and at
Baseline, prior to admission to study site, except for positive tests due to
prescribed drugs in hepatic impaired patients

7. Negative human immunodeficiency virus (HIV) antibody screens

8. Able to communicate well with the investigator, to understand and comply with the
requirements of the study. Understand and sign the written informed consent. Legal
authorized representatives are not permitted

Patients with Hepatic Impairment Only

9. Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment that
is not attributable to any other underlying disease

10. Patients assigned to a hepatic impairment group must be evaluable and meet criteria
for hepatic impairment per the Child-Pugh Clinical Assessment Score

Healthy subjects only

11. Healthy subjects will be identified after all hepatic impairment patients have been
enrolled and the healthy subject group will have similar distributions of age (by
hepatic impairment population quartiles), BMI (by hepatic impairment population
quartiles) and gender

12. Negative hepatitis panel (including hepatitis B surface antigen [HBsAg], hepatitis B
core antibody (anti-HBc), and hepatitis C virus antibody [anti-HCV])

Exclusion Criteria:

Study participants meeting any of the following criteria during Screening or Baseline
evaluations will be excluded from entry into or continuation in the study:

All Study Participants

1. Participation in any clinical investigation within 4 weeks prior to Check-in or longer
if required by local regulation

2. Participation in any clinical investigation involving receipt of investigational study
drug within 5 half-lives or 30 days prior to Check-in (Day -1) (whichever is longer)

3. Donation or loss of 400 mL or more of blood within 8 weeks prior to Check-in

4. Significant illness within the two weeks prior to Check-in

5. A past medical history of clinically significant ECG abnormalities, presence of an
abnormal ECG (which in the Investigator's opinion is clinically significant), QTcF
>450 msec, or has concomitant conditions that significantly increase risk for QTc
interval prolongation such as heart failure or family history of long QT interval
syndrome)

6. Resting heart rate < 50 beats per minute (bpm)

7. Alcohol ingestion within 72 hours of Check-in

8. Urine Cotinine levels = 150 ng/mL

9. Use of potent inducers of CYP3A4 (Appendix 4) within 30 days of Check-in

10. Use of potent inhibitors of CYP3A4 (Appendix 4) within 15 days of Check-in

11. Use of over-the-counter medications (except as prescribed by a physician), vitamins,
or phytotherapeutic/herbal/plant-derived preparations within 14 days of Check-in

12. Consumption of grapefruit- and grapefruit-containing products is not permitted within
7 days of Check-in

13. History of clinically significant drug allergy; history of atopic allergy (asthma,
urticaria, eczematous dermatitis). A known hypersensitivity to the study drug, study
drug excipients, or drugs similar to the study drug

14. Any surgical or medical condition which might significantly alter the absorption,
distribution, metabolism or excretion of drugs or which may jeopardize the study
participant in case of participation in the study. The investigator should be guided
by evidence of any of the following:

- history of inflammatory bowel syndrome




Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myelofibrosis

Intervention(s)

Drug: Pacritinib

Primary Outcome(s)

To characterize the pharmacokinetic profile of a single 400-mg dose of pacritinib and its major metabolites in patients with hepatic impairment as compared to gender-, age-, and body mass index -matched healthy subjects with normal liver function [Time Frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose]

Secondary Outcome(s)

To evaluate the safety of pacritinib and tolerability of a single 400-mg dose of pacritinib in patients with hepatic impairment and healthy subjects; [Time Frame: 00:00 of ICF signature until 1 min before IP admin and from the date-time of IP administration until 23:59 of the day of last contact]

Secondary ID(s)

PAC103

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

SGS S.A.