Study to Evaluate the Safety, Tolerability, and PK of Pacritinib

NCT05552183 | Completed Phase 1 FDA Drug

• 1 other identifier: PAC110
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1 study designed to assess the effect of hepatic insufficiency on the PK of pacritinib by study of 14-day BID dosing of pacritinib in subjects with moderate and severe hepatic impairment compared to healthy matched control subjects with normal liver function. Safety and tolerability of multiple day dosing of pacritinib in the subject populations will also be evaluated.

Conditions

Hepatic Impairment

Keywords

Pacritinib

Outcome Measures

Primary Outcomes (14)

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 1- (Day 1: Cmax)

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 1(Day 1: Tmax)

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 1( AUC0-12)

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14: Cmax,

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14: Tmax,

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 t1/2

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 CL/F

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 AUC0 t

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 AUC0 -12

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 λZ,

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 Vz/F

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 f/u

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 ARCmax

• PK

  To characterize and compare the steady-state PK profile of multiple doses (14 days) of 200 mg BID pacritinib in subjects with moderate and severe hepatic impairment with that of healthy matched control subjects with normal liver function.

  Day 14 ARAUC0-12

Secondary Outcomes (5)

• Incidence of adverse events

  Day 1-44

• Incidence of clinical laboratory abnormalities

  Day 1-21

• Incidence of vital sign abnormalities

  Day 1-21

• Incidence of ECG abnormalities

  Day1-21

• Incidence of physical examination abnormalities

  Day 1-21

Study Arms (3)

Moderate Hepatic Impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment based on Child-Pugh Class B score of 7-9 will receive 14 days of 200 mg BID pacritinib.

Drug: oral dose of 200 mg pacritinib twice daily (BID)

Severe Hepatic Impairment

EXPERIMENTAL

Subjects with severe hepatic impairment based on Child-Pugh Class C score of 10-15 will receive 14 days of 200 mg BID pacritinib.

Drug: oral dose of 200 mg pacritinib twice daily (BID)

Normal Hepatic Function

EXPERIMENTAL

Healthy subjects who have normal hepatic function with age (± 10 years; ≥ 18 years old and ≤ 85 years old), BMI (±20%), and sex, matching with the moderate and severe hepatic impairment cohorts will receive 14 days of 200 mg BID pacritinib.

Drug: oral dose of 200 mg pacritinib twice daily (BID)

Interventions

oral dose of 200 mg pacritinib twice daily (BID) DRUG

Subjects will receive 200 mg BID pacritinib for 14 days.

Moderate Hepatic Impairment; Normal Hepatic Function; Severe Hepatic Impairment

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent.
• Able to communicate well with the investigator and understands and agrees to comply with all protocol requirements.
• Is male or female ≥18 to ≤85 years of age, inclusive, at screening.
• Has a BMI 18.0 to 42.0 kg/m2, inclusive, at screening.
• Female subjects of childbearing potential must be surgically sterile, or postmenopausal, or agree use an acceptable method of birth control from the time of ICF or 10 days prior to check-in and until 30 days after Day 21. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at check-in.
• Male subjects with female partners of childbearing potential must be vasectomized, be willing to use an acceptable method of birth control, or to practice abstinence during the study from check-in until 90 days following Day 21.
• Male subjects must refrain from sperm donation from check-in until 90 days following Day 21.
• Has chronic (\>6 months) and stable hepatic impairment (ie, no acute episodes of illness within 30 days prior to screening due to deterioration of hepatic function) as assessed by a Child-Pugh classification score of moderate (7 to 9 points) or severe (10 to 15 points).
• Is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead ECG results, and physical examination findings, except for findings that, as judged by the investigator, are consistent with the subject's hepatic impairment or other stable concomitant medical conditions at screening and check-in.
• Has normal hepatic function.
• Must match a subject in Group 1 and/or Group 2, with respect to sex, age (±10 years), and BMI (±20%).
• Is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead ECG results, and physical examination findings at screening and check-in.

You may not qualify if:

• Has a history or clinical manifestations of a significant neurological, renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or psychiatric disease that would preclude study participation, as judged by the investigator.
• Has any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the subjects participation in the study. The investigator should be guided by evidence of any of the following:
• History of inflammatory bowel disease
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection (esophageal varix surgery is allowable)
• Clinical evidence of pancreatic injury or pancreatitis
• Evidence of urinary obstruction or difficulty in voiding at screening
• Has a baseline seated systolic blood pressure \>160 mm Hg or ≤90 mm Hg and a diastolic blood pressure of \>100 mm Hg or ≤50 mm Hg, inclusive, at screening and check in unless deemed not clinically significant by the investigator, as approved by the sponsor.
• Has a baseline seated pulse rate of \<50 bpm or \>100 bpm and/or an oral body temperature \<35.0°C or \>37.5°C when vital signs are measured at screening and check in.
• Has a significant QT interval prolongation (QTcF of \>480 msec) or other risks for QT prolongation at screening or check-in.
• Has a history of being immunocompromised or has a positive serum test result for HIV types 1 or 2 antibodies at screening.
• Has had a significant illness within the 2 weeks prior to check-in.
• Has a history of alcoholism, drug abuse, or alcohol withdrawal within 3 months before screening, or excessive alcohol consumption (regular alcohol intake \>21 units per week for male subjects and \>14 units of alcohol per week for female subjects) (1 unit is equal to approximately ½ pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits).
• Is unable or unwilling to abstain from alcohol from 72 hours prior to check-in until Day 21.
• Is unable or unwilling to abstain from caffeine, xanthine-containing beverages or food (eg, coffee, tea, chocolate, and caffeinated sodas, colas) from check in until Day 21.
• Has consumed grapefruit, grapefruit juice, Seville oranges, or products containing any of these, from 7 days prior to check-in to the study site until Day 21.

Sponsors & Collaborators

• CTI BioPharma: lead
• PPD Development, LP: collaborator

Study Sites (2)

Site 2

Orlando, Florida, 32809, United States

Location

Site 1

San Antonio, Texas, 78215, United States

Location

Study Officials

• Buckley

  Sobi, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 13, 2022
• First Posted: September 23, 2022
• Study Start: December 12, 2022
• Primary Completion: June 10, 2024
• Study Completion: June 10, 2024
• Last Updated: October 21, 2024

Record last verified: 2024-10

Locations

US (2)