Pharmacokinetics of 14C-labeled IsavuconazolePhase 1NCT01813461
Study to Evaluate the Pharmacokinetics of 14C-labeled Isavuconazole Following a Single Oral Dose of 14C-labeled Prodrug Isavuconazonium Sulfate (BAL8557) in Healthy Male Subjects
A Phase 1 study testing 14C-labeled prodrug isavuconazonium sulfate in people with Pharmacokinetics of 14C-labeled Isavuconazole and Healthy Subjects, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled isavuconazole and the routes of excretion and the extent of metabolism of 14C-labeled prodrug BAL8557. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of 14C-labeled Isavuconazole, Healthy Subjects
- What is being tested?
- 14C-labeled prodrug isavuconazonium sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Nov 2012
- 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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
- The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1; or, if abnormal, the abnormality is not clinically significant, including a QT interval corrected for heart rate using Fridericia's formula (QTcF) of 430 msec or less.
- The subject's clinical laboratory test results at Screening and Day 1 are within normal limits or not clinically significant.
- Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be within the normal range.
- The subject is surgically sterile or agrees to using a highly effective method of contraception to prevent pregnancy during the study and for at least 90 days after dosing on Day 1, and the subject agrees to not donate any sperm for at least 90 days after dosing on Day 1.
Who cannot join
- The subject has any clinically significant disease history or condition that precludes him from participating in the trial.
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome
- The subject has a history of bowel obstruction, swallowing disorder, severe gastrointestinal disorders, major gastrointestinal surgery, actively bleeding hemorrhoids, or gastric/duodenal ulcers.
- The subject has irregular bowel habits (< 1 bowel movement per day).
- The subject has had nuclear medicine procedures, computed tomography scans, or significant x-rays (other than dental) within the past 12 months, has had significant occupational radiation exposure, or participated in a radio-labeled study within the last 6 months or participated in more than one radio-labeled study within the last 12 months.
- The subject has a positive test for hepatitis B surface antigen or hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus (HIV).
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- The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission on Day -1.
- The subject has received a vaccination within the last 30 days prior to study drug administration.
- The subject has a known or suspected allergy to any of the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the Investigator), or a history of severe anaphylactic reactions.
- The subject has used tobacco or nicotine containing products in the last 6 months.
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medication within 1 week prior to Day -1, with the exception of occasional use of acetaminophen up to 2 g/day.
- The subject has participated in any interventional clinical study or has received any investigational agent within 30 days or 5 half-lives, whichever is longer, prior to the initiation of Screening.
- The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.
- The subject has taken part in strenuous exercise within 3 days prior to dosing on Day 1.
- The subject anticipates an inability to abstain from caffeine or alcohol use for 48 hours prior to clinic admission on Day -1 and throughout the duration of the study; or from grapefruit, grapefruit juice, star fruit, or Seville oranges or any products containing these items from 72 hours prior to clinic admission on Day -1 and throughout the duration of the study.
- The subject has a recent history (within the last 2 years) of drug or alcohol abuse or a positive drug screen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Open-Label Mass Balance Study to Evaluate the Pharmacokinetics of Isavuconazole After a Single Oral Dose of 14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects
The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled isavuconazole and the routes of excretion and the extent of metabolism of 14C-labeled prodrug BAL8557.
Read the detailed description
Subjects will be admitted to and stay in a clinical research unit for 23 days. On Day 1, they will receive a single oral dose of BAL8557 and throughout the study period the excretion and metabolism of the study drug will be monitored.
- Being tested
- 14C-labeled prodrug isavuconazonium sulfate
- Keywords
- BAL8557, 14C-labeled isavuconazole, 14C-labeled prodrug isavuconazonium sulfate (BAL8557)/([cyano-14C]ASP9766 sulfate)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
14C-labeled prodrug isavuconazonium sulfateDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| 14C-labeled prodrug isavuconazonium sulfate | Experimental | single dose Receives: Drug: 14C-labeled prodrug isavuconazonium sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in emesis (if applicable)
Measured: After study drug administration Days 1 up through 29
Radioactivity ratio blood/plasma
Measured: Day 1
Excretion ratio and cumulative excretion of radioactivity in urine
Measured: Pre-dose and after dosing collection times: 0 to 6, 6 to 12, 12 to 24, and in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until discharge
Excretion ratio and cumulative excretion of radioactivity in feces
Measured: Pre-dose and after dosing in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until the day of discharge
Secondary outcomes (3)
Pharmacokinetic profile of isavuconazole in plasma: AUCinf, AUClast, Cmax, tmax, Apparent body clearance after dosing (CL/F), Apparent volume of distribution (Vz/F), t1/2
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Pharmacokinetic Profile of isavuconazole in urine: Ae, Ae%, CLR
Amount excreted (Ae), Percent of unchanged drug excreted into the urine (Ae%), Renal clearance (CLR)
Measured: Pre-dose and 0 to 6, 6 to 12, 12 to 24, in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until day of discharge
Metabolic profile of isavuconazole and possible metabolites in plasma, urine, and feces
Measured: 8, 24,72, 144, and 312 hours after dosing. If subjects are not discharged on Day 22, samples will be taken at 504 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2013 (estimated)
- Study startOct 2012
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics of 14C-labeled IsavuconazoleStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01813461
- Sponsor's protocol ID
- 9766-CL-0016
- Status last verified
- Mar 2013
- First submitted
- 15 Mar 2013
- Last updated
- 19 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-Label Mass Balance Study to Evaluate the Pharmacokinetics of Isavuconazole After a Single Oral Dose of 14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT01813461
- Acronym / sponsor ID
- 9766-CL-0016
- Keywords
- BAL8557, 14C-labeled isavuconazole, 14C-labeled prodrug isavuconazonium sulfate (BAL8557)/([cyano-14C]ASP9766 sulfate)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Study start
- Oct 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 19 Mar 2013 (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.
The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled isavuconazole and the routes of excretion and the extent of metabolism of 14C-labeled prodrug BAL8557.
Detailed description
Subjects will be admitted to and stay in a clinical research unit for 23 days. On Day 1, they will receive a single oral dose of BAL8557 and throughout the study period the excretion and metabolism of the study drug will be monitored.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 14C-labeled prodrug isavuconazonium sulfate | Experimental | Drug: 14C-labeled prodrug isavuconazonium sulfatesingle dose |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
- The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1; or, if abnormal, the abnormality is not clinically significant, including a QT interval corrected for heart rate using Fridericia's formula (QTcF) of 430 msec or less.
- The subject's clinical laboratory test results at Screening and Day 1 are within normal limits or not clinically significant.
- Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be within the normal range.
- The subject is surgically sterile or agrees to using a highly effective method of contraception to prevent pregnancy during the study and for at least 90 days after dosing on Day 1, and the subject agrees to not donate any sperm for at least 90 days after dosing on Day 1.
Key exclusion criteria (16 listed)
- The subject has any clinically significant disease history or condition that precludes him from participating in the trial.
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome
- The subject has a history of bowel obstruction, swallowing disorder, severe gastrointestinal disorders, major gastrointestinal surgery, actively bleeding hemorrhoids, or gastric/duodenal ulcers.
- The subject has irregular bowel habits (< 1 bowel movement per day).
- The subject has had nuclear medicine procedures, computed tomography scans, or significant x-rays (other than dental) within the past 12 months, has had significant occupational radiation exposure, or participated in a radio-labeled study within the last 6 months or participated in more than one radio-labeled study within the last 12 months.
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 |
|---|---|---|
| 14C-labeled prodrug isavuconazonium sulfateoral | Drug | 14C-labeled prodrug isavuconazonium sulfate |
Primary outcome
Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Radioactivity in emesis (if applicable)
Time frame: After study drug administration Days 1 up through 29
Radioactivity ratio blood/plasma
Time frame: Day 1
Excretion ratio and cumulative excretion of radioactivity in urine
Time frame: Pre-dose and after dosing collection times: 0 to 6, 6 to 12, 12 to 24, and in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until discharge
Excretion ratio and cumulative excretion of radioactivity in feces
Time frame: Pre-dose and after dosing in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until the day of discharge
3 secondary outcomes
Pharmacokinetic profile of isavuconazole in plasma: AUCinf, AUClast, Cmax, tmax, Apparent body clearance after dosing (CL/F), Apparent volume of distribution (Vz/F), t1/2
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing
Pharmacokinetic Profile of isavuconazole in urine: Ae, Ae%, CLR
Time frame: Pre-dose and 0 to 6, 6 to 12, 12 to 24, in 24 hour intervals up to 504 hours after radioactive dose. If subjects are not discharged on Day 22, sample collection will continue in 24 hour intervals until day of discharge
Metabolic profile of isavuconazole and possible metabolites in plasma, urine, and feces
Time frame: 8, 24,72, 144, and 312 hours after dosing. If subjects are not discharged on Day 22, samples will be taken at 504 hours after dosing
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 19 Mar 2013.
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.
Medical Director study director
Astellas Pharma Global Development, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 14C-labeled prodrug isavuconazonium sulfate in people with Pharmacokinetics of 14C-labeled Isavuconazole and Healthy Subjects, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
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 5 inclusion and 16 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 19 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf) (time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 216, 264, 312, 360, 408, 456, and 504 hours after radioactive dose. If subjects are not discharged on Day 22, blood will be collected at 576 and 648 hours after dosing). The study lists 9 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 19 Mar 2013.