MyelofibrosisPhase 1NCT02807077
PK of Pacritinib in Patients With Mild, Moderate, Severe Renal Impairment and ESRD Compared to Healthy Subjects
A Phase 1 study testing Pacritinib in people with Myelofibrosis, run by CTI BioPharma at 3 sites in 3 countries.
Trial summary
This is a Phase 1 open label, single dose, 5 parallel-group study in which a single 400 mg dose of pacritinib will be administered orally to patients with renal impairment (mild, moderate, severe, and patients with ESRD requiring hemodialysis) and sex-, age- and weight-matched healthy subjects.Patients with ESRD will… Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- Pacritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Nov 2014to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All Study Participants
- Male and/or female participants aged 18 to 85 years (inclusive)
- Male, non-fertile female or female of childbearing potential 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 contraception from the time of signing the informed consent or 10 days prior to Check-in (Day -1) until 30 days after Study Completion. One of the following forms of contraception must 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: 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. Participants will refrain from sperm donation from Check-in (Day -1) until 90 days following Study Completion
- Body mass index (BMI) 18-33kg/m2 (inclusive) at Screening
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- Negative test for selected drugs of abuse (including alcohol) at Screening and at Check-in (Day - 1) for Groups 1-3 and 5. Negative test for selected drugs of abuse (including alcohol) is only required at Screening in Group 4
- Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and hepatitis C virus antibody [anti HCV]) and negative human immunodeficiency virus (HIV) antibody screens
- Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. Legal authorized representatives are not permitted
- Patients with Renal Impairment Only
- In addition to the inclusion criteria specified for "All Study Participants" above, patients with renal impairment must meet the following criteria:
- Have stable renal disease without evidence of progressive renal disease (i.e. no known significant change of eGFR for 12 weeks)
- mild renal impairment: eGFR 60-89 mL/min/1.73 m2
- moderate renal impairment: eGFR 30-59 mL/min/1.73 m2
- severe renal impairment: CrCl from eGFR 15-29 mL/min/1.73 m2
- ESRD: requiring dialysis and have been on a stable dialysis regimen for at least 6 months
- Renal function will be determined from Screening serum creatinine value using the MDRD Study equation
- Vital signs (after 5 minutes resting measured in the supine position) within the following ranges as guidance for the Investigator:
- oral body temperature between 35.0-37.8 °C
- systolic blood pressure, 95-180 mm Hg
- diastolic blood pressure, 55-95 mm Hg
- pulse rate, 50-95 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 or 10 mm Hg drop in diastolic blood pressure associated with symptomatic postural hypotension
- Healthy Subjects Only
- In addition to the inclusion criteria specified for "All Study Participants" above, healthy subjects must meet the following criteria:
- No history or clinical manifestation of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (e.g., celiac disease, peptic ulcer, gastro esophageal 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)
- Normal renal function, eGFR ≥90 mL/min/1.73m2 (determined by Screening serum creatinine using the MDRD Study equation)
- Matched with all enrolled patients with renal impairment for age classes in the 0-25, 26-50, 51-75, and 76-100 percentiles of age distribution
- Matched with all enrolled patients with renal impairment for weight (BMI) classes in the 0-25, 26-50, 51-75, and 76-100 percentiles of BMI distribution
- Matched according to the sex distribution of all enrolled patients with renal impairment
- Vital signs (after 5 minutes resting measured in the supine position) within the following ranges as guidance for the Investigator:
- 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, 45-90 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 or 10 mm Hg drop in diastolic blood pressure associated with symptomatic postural hypotension
Who cannot join
- All Study Participants
- Participants meeting any of the following criteria will be excluded from entry into or continuation in the study unless sponsor approval is obtained:
- Pregnant or lactating female
- Renal transplant at any time
- Liver cirrhosis or a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result
- History of immunodeficiency diseases, including a positive HIV antibody test result
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- Acute renal failure
- History of chronic or recurrent urinary tract infection active within the past 30 days
- History of pelvic irradiation within the past 30 days
- Alcohol related hepatic disease
- 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
- Any of the following within the past 6 months:
- myocardial infarction (MI) (if the Screening ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the subject can enter the study at the discretion of the Investigator and/or local medical monitor, with sponsor's permission)
- coronary artery bypass surgery or percutaneous coronary intervention
- unstable angina or stroke
- 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 increase risk for QTc interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
- Any medical or surgical conditions that might significantly interfere with the gastrointestinal absorption, distribution, metabolism, or excretion of the investigational drug. This includes any history of a significant disease of the gastrointestinal tract, pancreas, liver, kidneys, and/or blood-forming organs. It does not include appendectomy, cholecystectomy, hernia repair, or underlying renal disease or abnormalities that occur as a direct result of renal disease in the renal impairment patients or abnormalities that occur as a direct result of renal disease
- History of drug or alcohol abuse within the last 6 months, or evidence of recent drug or alcohol abuse as indicated by laboratory assays conducted during screening or baseline evaluations
- Heavy use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) and during the entire study, defined as urinary cotinine > 150 ng/mL
- 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 or inducers for 7 days prior to Check-in (Day -1) 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), 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) or from the time of signing the informed consent (females only) until 14 days after the final dose administration
- Use of any over-the-counter, non-prescription medications, vitamins, or minerals (except as prescribed by a physician), within 14 days prior to Check-in (Day -1) and during the entire study
- Use of phytotherapeutic/herbal/plant-derived preparations within 14 days prior to Check-in (Day -1) of and during the entire study
- Use of potent inducers of CYP3A4 within 30 days of Check-in (Day -1)
- Use of potent inhibitors of CYP3A4 within 15 days of Check-in (Day -1)
- Poor peripheral venous access
- Donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to Check-in (Day -1) and through entire study
- Receipt of blood products within 2 months prior to Check-in (Day -1)
- Any diarrhea or vomiting during the Screening period or at Check-in (Day -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
- Any of the following concomitant medications within 30 days of Check-in (Day -1) (unless cited otherwise below):
- potassium-sparing diuretics e.g. spironolactone, triamterene, amiloride (within 14 days of Check-in)
- class Ia, Ib and Ic or III anti-arrhythmics
- probenecid
- any medication that is contraindicated in moderate or severe renally impaired population
- any drug with a known and frequent toxicity to a major organ system within 3 months of Screening (i.e., cytostatic drugs)
- Any of the following (repeated and confirmed) laboratory abnormalities at Screening or Check-in:
- Clinically significant (as judged by the Investigator in consultation with the Sponsor) laboratory abnormalities except elevated blood urea nitrogen (BUN), elevated serum creatinine, hyperglycemia, and/or glycosuria
- Alanine aminotransferase (ALT)>1.5xULN
- Aspartate aminotransferase (AST)>1.5xULN
- Total bilirubin >1.3x ULN (unless due to Gilbert's Syndrome)
- Hemoglobin < 8 g/dL
- Laboratory testing may be repeated once prior to dosing (to rule out any possible laboratory error)
- Planned surgery during the study period
- Subjects who are deemed vulnerable by way of imprisonment, remand or detention
- Patients with Renal Impairment Only
- In addition to the exclusion criteria specified for "All Subjects" above, any patient with renal impairment who meets the following criteria will be excluded from entry into the study:
- Any condition that would compromise patients' safety during study participation
- Participants in Groups 1-3: Difficulty voiding or urinary tract obstruction at Check-in or undergoing any method of dialysis (hemodialysis, peritoneal dialysis)
- Screening physical exam or ECG finding considered of clinical significance by the Investigator, or a laboratory evaluation outside of the normal reference range with the exception of values that are related to renal impairment
- Any significant acute or chronic disease (except renal impairment) which is unstable or can interfere with the objectives of the study
- Any change in stable dose regimens, either over-the-counter or prescription, for chronic medical conditions (e.g. diabetes, dyslipidemia, renal impairment) within 4 weeks preceding dosing
- Healthy Subjects Only
- In addition to the exclusion criteria specified for "All Study Participants" above, any healthy subject who meets the following criteria will be excluded from entry into the study:
- Any screening or baseline physical exam, EKG, or laboratories outside the normal range and deemed clinically significant by the Investigator. Results deemed not clinically significant by the Investigator in consultation with the Sponsor are allowable.
- Use of any prescription medications and/or products within 14 days prior to Check-in (Day -1) and during the entire study
- History of renal impairment
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Phase 1 Open-Label, Single-Dose, Parallel-Group Study to Determine the Pharmacokinetics of Pacritinib in Patients With Mild, Moderate, and Severe Renal Impairment and End-Stage Renal Disease (ESRD) Compared to Healthy Subjects
This is a Phase 1 open label, single dose, 5 parallel-group study in which a single 400 mg dose of pacritinib will be administered orally to patients with renal impairment (mild, moderate, severe, and patients with ESRD requiring hemodialysis) and sex-, age- and weight-matched healthy subjects.Patients with ESRD will receive a single 400 mg dose of pacritinib during 2 different treatment periods: Dialysis and Inter-Dialysis. The primary objective of the study is to evaluate the pharmacokinetics and safety of pacritinib in renal impairment.
Read the detailed description
Groups 1, 2, and 3 will consist of 8 patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib.
Group 4 will consist of 8 patients with ESRD requiring hemodialysis who have been on a stable dialysis regimen for at least 6 months. In this cohort only, patients will participate in 2 treatment periods, Dialysis and Inter-Dialysis, separated by a 14-day period between pacritinib administration. In the Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered 4 hours prior to each patient's normally scheduled hemodialysis. In the Inter-Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered immediately after the end of the patient's normally scheduled hemodialysis session.
Group 5 will consist of 8 healthy subjects enrolled to match the sex-, age-, and weight of the patients with mild, moderate, and severe renal impairment and patients with ESRD enrolled in the study. Healthy subjects will be administered a single 400 mg dose of pacritinib.
- Conditions
- Myelofibrosis
- Being tested
- Pacritinib
- Keywords
- Healthy subjects
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PacritinibDrug
Group 1, 2, 3, and 5 will be administered single oral 400-mg dose of pacritinib. Subjects in the Group 4 received a single 400-mg dose of pacritinib during two different treatment periods: Dialysis and Inter-Dialysis
| Study group | Role | What they receive |
|---|---|---|
| Subjects with mild renal impairment | Experimental | Group 1, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. Receives: Drug: Pacritinib |
| Subjects with moderate renal impairment | Experimental | Group 2, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. Receives: Drug: Pacritinib |
| Subjects with severe renal impairment | Experimental | Group 3, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. Receives: Drug: Pacritinib |
| Subjects with ESRD | Experimental | Group 4, will consist of patients with ESRD requiring hemodialysis who have been on a stable dialysis regimen for at least 6 months. In this cohort only, patients will participate in 2 treatment periods, Dialysis and Inter-Dialysis, separated by a 14-day period between pacritinib administration. In the Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered 4 hours prior to each patient's normally scheduled hemodialysis. In the Inter-Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered immediately after the end of the patient's normally scheduled hemodialysis session. Receives: Drug: Pacritinib |
| Healthy subjects | Experimental | Group 5, will consist of 8 healthy subjects enrolled to match the sex-, age-, and weight of the patients with mild, moderate, and severe renal impairment and patients with ESRD enrolled in the study. Healthy subjects will be administered a single 400 mg dose of pacritinib. Receives: Drug: Pacritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum plasma concentration (Cmax)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The time to reach maximum plasma concentration (tmax)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
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).
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The apparent volume of distribution (Vd)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The apparent total body clearance (CL/F)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
Measured: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
Secondary outcomes (1)
Incidence of Treatment emergent Adverse Events
Adverse events, vital signs, physical examinations, clinical laboratory evaluations, and ECGs
Measured: Day 1 to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startNov 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- CTI BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Responsible party
- Sponsor
- Investigators
- Igor Codreanu, MD, Principal investigator, Republican Clinical HospitalGernot Klein, MD, Principal investigator, APEX GmbHMircea N Penescu, MD, Principal investigator, Carol Davila Nephrology Hospital Bucharest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02807077
- Sponsor's protocol ID
- PAC105
- Status last verified
- Oct 2018
- First submitted
- 3 May 2016
- Last updated
- 22 Oct 2018
- Results posted
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-Label, Single-Dose, Parallel-Group Study to Determine the Pharmacokinetics of Pacritinib in Patients With Mild, Moderate, and Severe Renal Impairment and End-Stage Renal Disease (ESRD) Compared to Healthy Subjects
- ClinicalTrials.gov ID
- NCT02807077
- Acronym / sponsor ID
- PAC105
- Conditions
- Myelofibrosis
- Keywords
- Healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- CTI BioPharmaIndustry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Study start
- Nov 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 21 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1 open label, single dose, 5 parallel-group study in which a single 400 mg dose of pacritinib will be administered orally to patients with renal impairment (mild, moderate, severe, and patients with ESRD requiring hemodialysis) and sex-, age- and weight-matched healthy subjects.Patients with ESRD will receive a single 400 mg dose of pacritinib during 2 different treatment periods: Dialysis and Inter-Dialysis. The primary objective of the study is to evaluate the pharmacokinetics and safety of pacritinib in renal impairment.
Detailed description
Groups 1, 2, and 3 will consist of 8 patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib.
Group 4 will consist of 8 patients with ESRD requiring hemodialysis who have been on a stable dialysis regimen for at least 6 months. In this cohort only, patients will participate in 2 treatment periods, Dialysis and Inter-Dialysis, separated by a 14-day period between pacritinib administration. In the Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered 4 hours prior to each patient's normally scheduled hemodialysis. In the Inter-Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered immediately after the end of the patient's normally scheduled hemodialysis session.
Group 5 will consist of 8 healthy subjects enrolled to match the sex-, age-, and weight of the patients with mild, moderate, and severe renal impairment and patients with ESRD enrolled in the study. Healthy subjects will be administered a single 400 mg dose of pacritinib.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Subjects with mild renal impairment | Experimental | Drug: PacritinibGroup 1, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. |
| Subjects with moderate renal impairment | Experimental | Drug: PacritinibGroup 2, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. |
| Subjects with severe renal impairment | Experimental | Drug: PacritinibGroup 3, will consist of patients each with mild, moderate, or severe renal disease, respectively, based on their estimated glomerular filtration rate (eGFR, calculated by the Modification of Diet in Renal Disease [MDRD] study equation). Each of these patients will receive a single 400 mg dose of pacritinib. |
| Subjects with ESRD | Experimental | Drug: PacritinibGroup 4, will consist of patients with ESRD requiring hemodialysis who have been on a stable dialysis regimen for at least 6 months. In this cohort only, patients will participate in 2 treatment periods, Dialysis and Inter-Dialysis, separated by a 14-day period between pacritinib administration. In the Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered 4 hours prior to each patient's normally scheduled hemodialysis. In the Inter-Dialysis Treatment Period, a single 400 mg dose of pacritinib will be administered immediately after the end of the patient's normally scheduled hemodialysis session. |
| Healthy subjects | Experimental | Drug: PacritinibGroup 5, will consist of 8 healthy subjects enrolled to match the sex-, age-, and weight of the patients with mild, moderate, and severe renal impairment and patients with ESRD enrolled in the study. Healthy subjects will be administered a single 400 mg dose of pacritinib. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- All Study Participants
- Male and/or female participants aged 18 to 85 years (inclusive)
- Male, non-fertile female or female of childbearing potential using a medically approved birth control method
- Body mass index (BMI) 18-33kg/m2 (inclusive) at Screening
- Negative test for selected drugs of abuse (including alcohol) at Screening and at Check-in (Day - 1) for Groups 1-3 and 5. Negative test for selected drugs of abuse (including alcohol) is only required at Screening in Group 4
Key exclusion criteria (60 listed)
- All Study Participants
- Participants meeting any of the following criteria will be excluded from entry into or continuation in the study unless sponsor approval is obtained:
- Pregnant or lactating female
- Renal transplant at any time
- Liver cirrhosis or a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PacritinibGroup 1, 2, 3, and 5 will be administered single oral 400-mg dose of pacritinib. Subjects in the Group 4 received a single 400-mg dose of pacritinib during two different treatment periods: Dialysis and Inter-Dialysis | Drug | Healthy subjects, Subjects with ESRD, Subjects with mild renal impairment, Subjects with moderate renal impairment, Subjects with severe renal impairment |
Primary outcome
The maximum plasma concentration (Cmax)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
The time to reach maximum plasma concentration (tmax)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
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: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
The apparent volume of distribution (Vd)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
The apparent total body clearance (CL/F)
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule in patients with renal impairment and matched healthy subjects
1 secondary outcome
Incidence of Treatment emergent Adverse Events
Time frame: Day 1 to Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Igor Codreanu, MD principal investigator
Republican Clinical Hospital
Gernot Klein, MD principal investigator
APEX GmbH
Mircea N Penescu, MD principal investigator
Carol Davila Nephrology Hospital Bucharest
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pacritinib in people with Myelofibrosis, run by CTI BioPharma at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 60 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany, Moldova, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The maximum plasma concentration (Cmax) (time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose. Urine- 0-168 hr interval). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2018.