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Renal ImpairedPhase 1NCT04699877

A Study to Investigate the Effect of Severe Renal Impairment on Gilteritinib Compared to Healthy Participants With Normal Renal Function

A Phase 1 study testing Gilteritinib in people with Renal Impaired and Gilteritinib, run by Astellas Pharma Global Development, Inc. at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of the study was to evaluate the pharmacokinetics of a single oral dose of gilteritinib in male and female participants with severe renal impairment compared to healthy male and female participants with normal renal function. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
What is being tested?
Gilteritinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
4 sitesin 2 countries
Study dates
28 Jan 2021to 18 Jul 2022
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 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Participant is eligible for participation in the study if all of the following apply:
  • Participant has body mass index (BMI) range of 18.5 to 40.0 kg/m^2, inclusive and weighs at least 50 kg at screening.
  • Female participant is not pregnant and the following condition apply: Not a woman of childbearing potential (WOCBP)
  • Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 120 days after Investigational Product (IP) administration.
  • Male participant must not donate sperm during the treatment period and for 120 days after investigational product (IP) administration.
  • Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 120 days after IP administration.
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  • Participant has renal function defined by estimated glomerular filtration rate (eGFR) using modification of diet in renal disease (MDRD) formula:
  • Normal renal function with eGFR ≥ 90 mL/min per 1.73 m^2, or
  • Mild renal impairment with eGFR 60 to <90 mL/min per 1.73 m^2, or
  • Moderate renal impairment with eGFR 30 to <60 mL/min per 1.73 m^2, or
  • Severe renal impairment as defined by the National Kidney Foundation and by eGFR <30 mL/min per 1.73 m^2 and not on hemodialysis (preferably not higher than 20 mL/min per 1.73 m^2, with at least 50% of participants required to have eGFR ≤ 20 mL/min per 1.73 m^2).
  • Participant has adequate venous access to allow collection of study-related samples.
  • Participant agrees not to participate in another interventional study while participating in the present study.

Who cannot join

  • Participant will be excluded from participation in the study if any of the following apply:
  • Participant has received any investigational therapy within 28 days or 7 half-lives, whichever is longer, prior to day -1.
  • Participant has any condition which makes the participant unsuitable for study participation.
  • Female participant who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
  • Participant has a known or suspected hypersensitivity to gilteritinib or any components of the formulation used.
  • Participant has had previous exposure with gilteritinib.
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  • Participant has any of the liver function tests (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and total bilirubin [TBL]) ≥ 1.5 × upper limit of normal on day -1. In such a case, the assessment may be repeated once.
  • Participant has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to IP administration.
  • Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
  • Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of > 450 msec (for male and female participants) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate 12-lead electrocardiogram (ECG) may be taken.
  • Participant has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1.
  • Participant has a history of consuming > 14 units for male participants or > 7 units for female participants of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism 3 months prior to screening or drug/chemical/ substance abuse within 1 year prior to screening (note: 1 unit = 12 ounces of beer, 4 ounces of wine, 1 ounce of spirits/hard liquor) or the participant tests positive for alcohol at screening or on day -1.
  • Participant has used any inducer of cytochrome P450 (CYP)3A metabolism (e.g., St. John's Wort, barbiturates and rifampin) in the 3 months prior to day -1.
  • Participant has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days.
  • Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome.
  • Participant has a positive serology test for hepatitis A virus immunoglobulin M antibodies, hepatitis B surface antigen, hepatitis C virus antibodies or antibodies to human immunodeficiency virus type 1 and/or type 2 at screening. Participants with isolated hepatitis B core antibody (with negative hepatitis B surface antigen and negative hepatitis B surface antibody) may be eligible if hepatitis B DNA or hepatitis C RNA is undetectable.
  • Participant is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
  • Participant who has received any of the following drugs/products within 2 weeks prior to IP administration:
  • Strong or moderate CYP3A inhibitors (e.g., grapefruit, Seville oranges, ketoconazole or fluconazole)
  • Strong or moderate inhibitors and all inducers of P-glycoprotein
  • Substrates of multidrug and toxin extrusion 1
  • Drugs that target serotonin 5-hydroxytryptamine receptor 1 or 5-hydroxytryptamine receptor 2B
  • Participant has a positive result for SARS-CoV-2 polymerase chain reaction (PCR) test during screening.
  • Participant has clinical signs and symptoms consistent with COVID-19 infection, e.g., fever, dry cough, dyspnea, sore throat, muscle or body aches and gastrointestinal symptoms or confirmed infection by appropriate SARS-CoV-2 PCR test within the 4 weeks prior to screening.
  • Additional criteria for participants with mild, moderate and severe renal impairment:
  • Participant who has a history of any clinically significant illness (other than renal disease and conditions related to renal disease, such as stable diabetes and stable hypertension), medical condition or laboratory abnormality within 3 months prior to screening which precludes the participant from study participation.
  • Participant has a mean pulse rate < 40 or > 90 bpm; mean systolic blood pressure (SBP) < 90 or > 160 mmHg; mean diastolic blood pressure (DBP) < 50 or > 100 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes; pulse rate will be measured automatically) on day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
  • Participant who has had a change in dose regimen of medically required medication(s) in the 2 weeks prior to IP administration (permitted concomitant medications) and/or participant for whom dose changes are likely to occur during the study (minor dose changes are allowed in agreement with the sponsor) and/or participant has used nonpermitted concomitant medication(s) (including, but not limited to vitamins, hormonal contraceptives and natural and herbal remedies) in the 3 weeks prior IP administration, except for topical dermatological products (including corticosteroid products) and hormone replacement therapy (HRT).
  • Participant who requires or is likely to require any new concomitant medications during the course of the study.
  • Participant who has a renal disease secondary to malignancy.
  • Participant who has a fluctuating or rapidly deteriorating renal function within 4 weeks prior to IP administration, as indicated by strongly varying or worsening clinical and/or laboratory signs of renal impairment within the screening period.
  • Participant has a hemoglobin result of < 8.5 g/dL.
  • Participant has a functioning kidney transplant.
  • Participant has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 or the participant tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids,cocaine and/or opiates) at screening or on day -1, unless the positive result is due to an approved prescription medication.
  • Additional criteria for healthy participants with normal renal function:
  • Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.
  • Participant has any clinically significant abnormality following the physical examination, ECG and protocol-defined clinical laboratory tests at screening or on day -1.
  • Participant has a mean pulse rate < 45 or > 90 bpm; mean SBP > 150 mmHg; mean DBP > 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes; pulse rate will be measured automatically) on day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
  • Participant has used any prescribed or nonprescribed drugs (including, but not limited to vitamins, hormonal contraceptives and natural and herbal remedies) in the 2 weeks prior to IP administration, except for occasional use of acetaminophen (up to 2 g/day), topical dermatological products (including corticosteroid products) and HRT.
  • Participant has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 or the participant tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) at screening or on day -1.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • National Institute of Clinical Research

    Garden Grove, California, 92844

  • Orlando Clinical Research Center

    Orlando, Florida, 32809

  • Orange County Research Institute

    Tustin, California, 92780

Other trials in United States

Bulgaria1 site

  • Site BG35901

    Sofia, 1000

Other trials in Bulgaria

About this study

Official title: A Phase 1 Open-label Study to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics, Safety and Tolerability of Gilteritinib Compared to Healthy Participants With Normal Renal Function

The purpose of the study was to evaluate the pharmacokinetics of a single oral dose of gilteritinib in male and female participants with severe renal impairment compared to healthy male and female participants with normal renal function. This study also evaluated safety and tolerability of a single oral dose of gilteritinib in male and female participants with severe renal impairment and healthy male and female participants with normal renal function. Part 2 of the study (mild and moderate renal impairment) was not conducted based on the final pharmacokinetic findings from part 1 (severe renal impairment).

Read the detailed description

This study was comprised of participants with severe renal impairment and normal renal function. Participants were residential for a single period of 14 days/13 nights. Participants were discharged from the clinical unit on day 14 on the condition that all required assessments had been performed and that there were no medical reasons for a longer stay in the clinical unit.

Being tested
Gilteritinib
Keywords
Gilteritinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GilteritinibDrug

    Also called ASP2215, XOSPATA®

    Oral

Study groups in NCT04699877
Study groupRoleWhat they receive
Gilteritinib (Severe Renal Impairment)ExperimentalParticipants with severe renal impairment received a single oral dose of 20 milligrams (mg) of gilteritinib on day 1, under fasting conditions.
Receives: Drug: Gilteritinib
Gilteritinib (Normal Renal Function)ExperimentalParticipants with normal renal function received a single oral dose of 20 mg of gilteritinib on day 1, under fasting conditions.
Receives: Drug: Gilteritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics (PK) of gilteritinib in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)

    Area under the concentration-time curve from the time of dosing extrapolated to time infinity was derived from the plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  2. PK of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

    Area under the concentration-time curve from the time of dosing to the last measurable concentration was derived from the plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  3. PK of gilteritinib in plasma: Maximum concentration (Cmax)

    Maximum plasma concentration of gilteritinib was derived from the plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  4. PK of gilteritinib in plasma: Apparent clearance (CL/F)

    CL/F derived from plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  5. Pk of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing extrapolated to the time infinity (unbound)(AUCinf,u)

    Area under the concentration-time curve from the time of dosing extrapolated to time infinity (unbound) was derived from plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  6. PK of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing to the last measurable concentration (unbound) (AUClast, u)

    Area under the concentration-time curve from the time of dosing to the last measurable concentration (unbound) was derived from plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

  7. PK of gilteritinib in plasma: Maximum concentration (unbound) (Cmax,u)

    Maximum concentration of gilteritinib (unbound) was derived from plasma samples.

    Measured: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

Secondary outcomes (1)

  1. Number of participants with Treatment Emergent Adverse Events (TEAEs)

    An AE is any untoward medical occurrence in a participant administered a study drug, which does not necessarily have to have a causal relationship with this treatment. It can, therefore, be any unfavorable and unintended sign, symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product whether considered related to the medicinal product. Treatment Emergent Adverse Event defined as an AE observed after starting administration of the study drug till 23 days.

    Measured: Up to Day 23

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2021
  2. Study start28 Jan 2021
  3. Primary completion18 Jul 2022
  4. Study completion18 Jul 2022

Resources

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
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04699877
Sponsor's protocol ID
2215-CL-0114
Other IDs
2020-003993-32
Status last verified
Oct 2024
First submitted
6 Jan 2021
Last updated
5 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gilteritinib in people with Renal Impaired and Gilteritinib, run by Astellas Pharma Global Development, Inc. at 4 sites in 2 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 13 inclusion and 40 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 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Bulgaria. 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?

Pharmacokinetics (PK) of gilteritinib in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf) (time frame: Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)). 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?

On the ClinicalTrials.gov record for NCT04699877.

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 5 Nov 2024.

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