Determine Pacritinib Pharmacokinetics in Impaired Hepatic Patients and Healthy Subjects

NCT02765724 | Completed Phase 1

• 1 other identifier: PAC103
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an open-label, parallel-group, single-dose study of the PK and safety of 400 mg pacritinib administered orally to patients with stable chronic liver disease and healthy control subjects.

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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

  Plasma concentrations of pacritinib and any major metabolites were determined by a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric assay. The lower limit of quantitation of the assay is 20 ng/mL for pacritinib and 4 ng/mL for PAC-M1 metabolite in plasma

  Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose

Secondary Outcomes (1)

• To evaluate the safety of pacritinib and tolerability of a single 400-mg dose of pacritinib in patients with hepatic impairment and healthy subjects;

  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

Study Arms (4)

Group 1

EXPERIMENTAL

Patients with mild hepatic impairment

Drug: Pacritinib

Group 2

EXPERIMENTAL

Patients with moderate hepatic impairment

Drug: Pacritinib

Group 3

EXPERIMENTAL

Patients with severe hepatic impairment

Drug: Pacritinib

Group 4

EXPERIMENTAL

Healthy subjects

Drug: Pacritinib

Interventions

Pacritinib DRUG

Pacritinib 400 mg (4 capsules of 100 mg each), single dose, oral administration

Also known as: Pacritinib 400mg capsule

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Study Participants
• Male and/or female from 18-85 years of age, inclusive
• 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
• 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)
• BMI between 18-40 kg/m2 (inclusive) at Screening
• 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
• 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
• Negative human immunodeficiency virus (HIV) antibody screens

You may not qualify if:

• 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
• Participation in any clinical investigation within 4 weeks prior to Check-in or longer if required by local regulation
• 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)
• Donation or loss of 400 mL or more of blood within 8 weeks prior to Check-in
• Significant illness within the two weeks prior to Check-in
• 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)
• Resting heart rate \< 50 beats per minute (bpm)
• Alcohol ingestion within 72 hours of Check-in
• Urine Cotinine levels ≥ 150 ng/mL
• Use of potent inducers of CYP3A4 (Appendix 4) within 30 days of Check-in
• Use of potent inhibitors of CYP3A4 (Appendix 4) within 15 days of Check-in
• 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
• Consumption of grapefruit- and grapefruit-containing products is not permitted within 7 days of Check-in
• 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

Sponsors & Collaborators

• CTI BioPharma: lead
• SGS S.A.: collaborator

Study Sites (2)

APEX GmbH

Munich, D-81241, Germany

Location

Republican Clinical Hospital

Chisinau, MD-2025, Moldova

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• James Dean, MD, PhD

  CTI BioPharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 9, 2016
• Study Start: January 1, 2015
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 6, 2020

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share

Locations

MO (1); DE (1)