Investigate Absorption, Metabolism, Excretion, and Mass Balance of Pacritinib

June 14, 2016 updated by: CTI BioPharma

A Phase 1, Open-Label Study to Investigate the Absorption, Metabolism, Excretion, and Mass Balance of [14C] Pacritinib Following a Single Oral Dose in Healthy Male Subjects

This study is an open-label, absorption, metabolism, excretion, and mass balance study of 400 mg [14C]pacritinib (containing 100 μCi radioactivity) administered orally as a single dose to 6 healthy male subjects following at least a 10-hour fast (not including water) on Day 1.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The present study is designed to investigate the absorption, metabolism, excretion as well as safety/tolerability of pacritinib following the administration of a single oral dose to healthy male volunteers. The pacritinib dose is administered with a [14C]-labeled form to enable detection and quantitation of dose-related material independent of possible biotransformation. The study design allows detection of potential human specific metabolites that have not been detected in the animal species. Subjects are confined at the clinical site from the time of Check-in until Day 14 post-dose, but may be discharged from the clinical site between Day 10 and 13 post-dose if study discharge criteria are met (i.e. completion of sufficient radioactivity excretion). All remaining subjects will be discharged from the clinical site on Day 14 post-dose irrespective of the study discharge criteria. The data obtained in this study will be used for the further clinical development of the compound.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • QPS Netherlands B.V.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Non-smoking men between 18 and 55 years of age (inclusive)
  • ECG within normal limits (according to the criteria used by QPS Netherlands BV including QTc interval (less than or equal to 450 m/sec)
  • Normal vital signs measurements [defined as blood pressure (BP) between 90-140 mmHg systolic and 50-90 mmHg diastolic, resting heart rate (HR) between 40-100 beats/min, temperature (T) less than or equal to 37.6 degree C])
  • Body mass index of 19.0-29.0 kg/m2 inclusive
  • Negative history of drug abuse or alcoholism within 1 year prior to Day 1
  • Negative tests on drug and alcohol screen at Screening and Check-in
  • Negative hepatitis panel including hepatitis B-surface antigen HBsAg], hepatitis C antibody [anti-HCV] and negative human immunodeficiency virus antibody (HIV)
  • No clinical laboratory value outside of the normal reference range unless deemed not clinically significant by the Investigator in consultation with the Sponsor
  • Fertile male subjects and fertile female sexual partners of male subjects agree to use effective birth control methods throughout the entire study. Female partners of childbearing potential must use highly effective methods (defined as those resulting in a failure rate of <1% per year when used consistently and correctly). The contraceptive methods considered highly effective are intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release). Male subjects must use a condom with spermicide paste for the duration of the study and for 90 days after the EOS evaluation. When abstinence is used as a method of birth control, only true abstinence is acceptable, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Agreement to not donate sperm throughout the entire study and for 3 months after the end of the study
  • Willingness to comply with the protocol, including restrictions on diet, physical activity, and use of alcohol, medications, and other drugs during the study
  • Comprehend and willingness to sign an approved informed consent form for the study
  • At least one bowel movement a day

Exclusion Criteria:

  • Participation in another radioactive clinical trial within the past 12 months
  • Actively participating in an experimental therapy study or who have received experimental therapy within 90 days of Day 1
  • Use of any other prescription medication within 21 days of Day 1, unless approved by Sponsor
  • Use of over-the-counter (OTC) medications or nonprescription preparations (including vitamins, minerals and phytotherapeutic/herbal/plant-derived preparations) that is known to induce drug-metabolizing enzymes, including CYP450 enzymes within the 7 days preceding Day 1 (except for spermicidal/barrier contraceptive products and paracetamol)
  • Consumption of alcoholic beverages within 72 hours prior to Check-in (Day -1)
  • Consumption of grapefruit- and grapefruit-containing products within 7 days prior to Day 1
  • Consumption of xanthine containing beverages such as coffee, including energy drinks containing caffeine or tea within 2 days of Day 1
  • Clinically significant abnormal physical finding at Screening
  • Any severe acute or chronic medical condition, psychiatric condition, or laboratory abnormality that in the Investigator's opinion may increase the risk associated with study participation or administration of study treatment, or interfere with the interpretation of study results (such as gastrointestinal surgical history (except appendectomy), ileus or obstructive uropathy)
  • Diarrhea, nausea or vomiting within 7 days of Day 1
  • History of additional risk factors for torsade de pointes (TdP) (e.g. heart failure, hypokalemia defined as serum potassium <3.0 mmol/L, family history of Long QT Syndrome)
  • Any illness during the 4 weeks prior to Day 1, unless deemed NCS by the Principal Investigator
  • Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens)
  • Known history or presence of food allergies or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs
  • Any surgical procedures within 72 hours of Day 1
  • Blood draws of more than 400 mL during the conduct of any clinical study within 90 days prior to Day 1
  • Poor peripheral venous access
  • Donation of blood 30 days prior to Screening through end of study
  • Employment in a position that exposes the subject to radiation or requires that the subject's degree of radiation exposure be monitored (e.g. radiology technician)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Investigational: [14C] Pacritinib
All enrolled subjects are checked in the day before drug administration. Following at least a 10-hour fast (not including water), each subject will receive an oral dose of 400 mg [14C]pacritinib (containing 100 μCi radioactivity).
Drug: Pacritinib
400 mg [14C]pacritinib (containing 100 μCi radioactivity) administered orally as a single dose following at least a 10-hour fast (not including water) on Day 1

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The maximum plasma concentration (Cmax)
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The PK parameters for [14C] pacritinib will be derived by non-compartmental analysis of the plasma concentration-time profiles and the PK parameters for the metabolites will be calculated, as deemed appropriate, based on the results of quantitative profiling performed on selected plasma and pooled urine samples from individual subjects
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The time to reach maximum plasma concentration (tmax)
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The PK parameters for [14C] pacritinib will be derived by non-compartmental analysis of the plasma concentration-time profiles and the PK parameters for the metabolites will be calculated, as deemed appropriate, based on the results of quantitative profiling performed on selected plasma and pooled urine samples from individual subjects
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The area under the plasma concentration-time curve from time zero to time of the last measured concentration above the limit of quantification (AUC0-t)
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The PK parameters for [14C] pacritinib will be derived by non-compartmental analysis of the plasma concentration-time profiles and the PK parameters for the metabolites will be calculated, as deemed appropriate, based on the results of quantitative profiling performed on selected plasma and pooled urine samples from individual subjects
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The area under the plasma concentration-time curve from time zero to 48 hours (AUC0- 48h)
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The PK parameters for [14C] pacritinib will be derived by non-compartmental analysis of the plasma concentration-time profiles and the PK parameters for the metabolites will be calculated, as deemed appropriate, based on the results of quantitative profiling performed on selected plasma and pooled urine samples from individual subjects
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
Time Frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose every 24 hours thereafter until Day 10, no later than Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Treatment-emergent adverse events (AEs) and serious adverse events (SAEs), vital Signs, PE, clinical laboratory valuations, and ECGs
Time Frame: Day 1 through Day 42
Evaluate Safety and tolerability of a single oral dose of 400 mg [14C]pacritinib in healthy subjects
Day 1 through Day 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CTI BioPharma

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
QPS-Qualitix

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Khalid A Elaziz, MBBS, MD, QPS Netherlands BV

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 17, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PAC102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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