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About
The primary objective is to evaluate the cardiac safety of a single oral dose (400 mg) of pacritinib compared to placebo on the QT calculated using the Fridericia correction (QTcF) interval in healthy subjects.
Full description
This is a randomized, pacritinib- versus placebo-blind, placebo- and active-controlled, single-dose, single-center, 3-period crossover study to evaluate the cardiac safety of a single 400-mg dose of pacritinib compared to placebo, and to characterize the PK of pacritinib and major human metabolites of pacritinib. The study is blinded for pacritinib and placebo, and open-label for moxifloxacin.
Subjects were to receive 3 treatments (400 mg pacritinib, placebo, and 400 mg moxifloxacin) in a crossover fashion. Each treatment is administered as monotherapy during 1 of 3 treatment periods with a 7-day washout period between administration of each study medication. Screening occurred up to 28 days before Check-in (Day -1) of Period 1. On Day -1 of Period 1, subjects checked into the Clinical Research Unit (CRU) for baseline assessments and were confined to the CRU for the remainder of the study until Study Completion (Day 22)/Early Termination. Continuous 12-lead cardiodynamic ECG monitoring and recording was performed from predose (at least
1 hour before administration of study medication) through 24 hours after the administration of study medication, then for 15 minutes every 12 hours (on Days 2 to 7 of each period). Blood samples for PK analysis were also collected predose (Hour 0) and at each cardiodynamic ECG timepoint postdose. Safety endpoints (eg, adverse events [AEs], clinical laboratory evaluations, vital signs) were monitored throughout each period. Subjects were discharged at Study Completion (Day 22). Subjects were scheduled to return for a Follow-up Visit 14 days (±3 days) later on Day 36.
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Inclusion criteria
Exclusion criteria
presence of any of the following electrocardiographic abnormalities based on the safety ECG at Screening:
history of syncope, cardiac arrest, cardiac arrhythmias, torsades de pointes, structural heart disease, a family history of long QT syndrome, or ongoing cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade >3.0;
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 disease);
significant abnormalities in liver function tests (any/all of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase >1.5 x upper limit of normal [ULN]; gamma-glutamyl transferase >2 x ULN; or total bilirubin >1.3 x ULN), kidney function tests (serum creatinine > ULN), hypokalemia (defined as serum potassium <3.0 mEq/L) that is persistent and refractory to correction, or hypomagnesemia (defined as serum magnesium <1.4 mEq/L);
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;
history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
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;
history of Gilbert's Syndrome;
history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant;
history of alcoholism or drug addiction within 1 year prior to Check-in (Day -1) of Period 1;
use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) of Period 1 and during the entire study;
consumption of alcohol- or caffeine-containing foods and beverages for 72 hours prior to Screening and during the entire study;
consumption of grapefruit-containing foods and beverages or other potent cytochrome P450 (CYP)3A4 inhibitors for 72 hours prior to Screening and during the entire study;
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;
use of oral, implantable, injectable, or transdermal contraceptives within 10 days prior to Check-in (Day -1) of Period 1 or from the time of signing the informed consent (females only) until 14 days after the final dose administration;
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;
use of any over-the-counter, non-prescription medications, vitamins, or minerals within 7 days prior to Check-in (Day -1) of Period 1 and during the entire study;
use of phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1) of Period 1 and during the entire study;
poor peripheral venous access;
donation of blood from 30 days prior to Screening through Study Completion (Day 22)/ET, inclusive, or of plasma from 2 weeks prior to Screening through Study Completion (Day 22)/ET, inclusive;
receipt of blood products within 2 months prior to Check-in (Day -1) of Period 1;
any diarrhea or vomiting during the Screening period or at Check-in (Day -1) of Period 1;
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
Primary purpose
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Interventional model
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42 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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