To Evaluate the Cardiac Safety and PK Following a Single Oral Dose Administration of Pacritinib in Healthy Subjects

NCT02807207 | Completed Phase 1

• 1 other identifier: PAC107
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

To Study pharmacokinetics and Cardiac safety

Outcome Measures

Primary Outcomes (1)

• QT calculated using Fridericia correction (QTcF) interval

  To evaluate the cardiac safety of a single oral dose (400 mg) of pacritinib compared to placebo

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

Secondary Outcomes (7)

• Maximum observed concentration (Cmax)

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

• Treatment emergent Adverse events

  Day1 to Day 36

• time to Cmax (tmax)

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

• area under the concentration-time curve (AUC) from Hour 0 to the last measurable concentration (AUC0-t)

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

• AUC extrapolated to infinity (AUC0-∞)

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

Study Arms (6)

Sequence I

EXPERIMENTAL

treatment sequence: A/B/C

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Sequence II

EXPERIMENTAL

treatment sequence: A/C/B

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Sequence III

EXPERIMENTAL

treatment sequence: B/A/C

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Sequence IV

EXPERIMENTAL

treatment sequence: B/C/A

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Sequence V

EXPERIMENTAL

treatment sequence: C/A/B

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Sequence VI

EXPERIMENTAL

treatment sequence: C/B/A

Drug: A: pacritinib; Other: B: Placebo; Drug: C: moxifloxacin

Interventions

A: pacritinib DRUG

Treatment A

Also known as: A: pacritinib 400mg

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

B: Placebo OTHER

Treatment B

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

C: moxifloxacin DRUG

Treatment C

Also known as: C: moxifloxacin 400mg

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy males or females, between 18 and 55 years of age, inclusive, who are non-tobacco users;
• with BMI range from 18.0 to 32.0 kg/m2, inclusive;
• normal or not clinically significant 12-lead ECG, in the opinion of the Investigator;
• heart rate of 45 to 90 beats per minute (bpm), inclusive, after 5 minutes in the supine position;
• mean systolic blood pressure \<141 mmHg and mean diastolic blood pressure \<90 mmHg, average value for each taken in duplicate at Screening (a repeat duplicate set may be performed once at Screening);
• in good health, determined by no clinically significant findings from medical history, physical examination, and vital signs;
• \. 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;
• negative test for selected drugs of abuse (including alcohol) at Screening and at Check-in (Day -1 of Period 1);
• negative hepatitis panel (including hepatitis B surface antigen \[HBsAg\] and hepatitis C virus antibody \[anti-HCV\]) and negative HIV antibody screens;
• 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 (eg, 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) of Period 1 until 30 days after Study Completion (Day 22)/ET, one of the following forms of contraception: 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 contraceptives may not be used from the time of signing the informed consent or 10 days prior to Check-in (Day -1) of Period 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) of Period 1;
• males will either be sterile or agree to use, from Check-in (Day -1) of Period 1 until 90 days following Study Completion (Day 22)/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 will refrain from sperm donation from Check-in (Day -1) of Period 1 until 90 days following Study Completion (Day 22)/ET;
• able to comprehend and willing to sign an Informed Consent Form (ICF).

You may not qualify if:

• presence of any of the following electrocardiographic abnormalities based on the safety ECG at Screening:
• QTcF interval \>450 msec
• unusual T-wave morphology (such as bifid T-wave) or flattened low voltage T-waves
• PR interval \>210 msec or \<110 msec
• evidence of second- or third-degree atrioventricular block
• electrocardiographic evidence of complete left bundle branch block (LBBB), right bundle branch block, or incomplete LBBB or intraventricular conduction delay or QRS duration \>110 msec;
• 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;

Sponsors & Collaborators

• CTI BioPharma: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit Inc.

Evansville, Indiana, 47710, United States

Location

Study Officials

• Kelly Whitehurst, MD

  Covance Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: June 21, 2016
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 15, 2023

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)