Pharmacokinetics of IsavuconazolePhase 1NCT01555866
Study of the Effect of Renal Impairment on the Pharmacokinetics of Isavuconazole.
A Phase 1 study testing isavuconazole in people with Pharmacokinetics of Isavuconazole and Healthy Volunteers, run by Astellas Pharma Global Development, Inc. at 3 sites in United States.
Trial summary
This is a 2-part, open-label study, designed to evaluate the effect of renal disease on the pharmacokinetics of BAL4815 (active isavuconazole moiety) relative to the pharmacokinetics in healthy subjects with normal renal function. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of Isavuconazole, Healthy Volunteers, Renal Impaired
- What is being tested?
- isavuconazole
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2012to Apr 2013
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject must weigh at least 45 kg and have a body mass index of 18-35 kg/m2
- If female, the subject agrees to sexual abstinence, is surgically sterile, postmenopausal or using a medically acceptable double-barrier method to prevent pregnancy and agrees to continue using this method during the study and until 28 days after final study dug administration. Female subjects must not be lactating or pregnant as documented by a negative pregnancy test at Screening and Day -1
- If male, the subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method during the study and until 90 days after the end of the study
- The subject has good venous access
- Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after final study drug administration.
Who cannot join
- The subject has a previous history of any clinically significant gastro-intestinal, neurological, hepatic, pulmonary, metabolic, dermatologic, immunologic, cardiovascular, psychiatric, genitourinary, endocrine, hematological disorder or disease, malignancy excluding non-melanoma skin cancer or any other medical condition that would preclude participation in the study
- The subject has evidence of any cardiac conduction abnormalities
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia, torsade de pointes, structural heart disease, or family history of Long QT syndrome
- The subject has a supine systolic blood pressure less than 90 or greater than 160 mmHg, and diastolic blood pressure less than 50 or greater than 90 mmHg, or pulse rate less than 40 or greater than 100 beats per minute, either at Screening and Day -1
- The subject has a history of consuming more than 14 units of alcoholic beverages per week, has a history of alcohol abuse within the past 2 years prior to Screening, or has a positive screen for alcohol at Screening or Day -1. (NOTE: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor.)
- The subject has a positive test for alcohol or drugs of abuse at Screening or Day-1, unless it is an expected result due to an approved concomitant medication for subjects with renal impairment
Show all 17Show fewer
- The subject has used nicotine patches or any tobacco-containing products within 1 month prior to Day-1 or is a smoker, defined as greater than 10 cigarettes per week
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Screening, or over-the-counter medication within 14 days prior to Screening (with the exception of acetaminophen up to 2 grams/day)
- The subject anticipates an inability to abstain from caffeine or alcohol for 48 hours prior to Day -1 and throughout the duration of the study
- The subject anticipates an inability to abstain from grapefruit, Seville oranges, star fruit, or any products containing these items from 72 hours prior to Day -1 and throughout the duration of the study
- The subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 7 days prior to Day -1
- The subject has been vaccinated within the last 30 days prior to Screening
- The subject has a positive test for hepatitis C antibody or hepatitis B surface antigen at Screening or a known history of human immunodeficiency virus
- The subject has a known or suspected hypersensitivity to isavuconazole, the azole class of compounds, or any components of the study drugs
- The subject has received an experimental agent within 30 days or ten half-lives, whichever is longer, prior to Screening
- The subject has had any significant blood loss, donated one or more units (450 mL) of blood or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to Day -1
- The subject has any other condition, which in the opinion of the investigator, precludes the subject's participation in the trial
Trial locations and contacts
3 sites in 1 country.
United States3 sites
DaVita Research
Denver, Colorado, 80228
Clinical Pharmacology Miami
Miami, Florida, 33014
DaVita Clinical Research
Minneapolis, Minnesota, 55404
About this study
Official title: A Phase 1 Open Label, 2 Part, Parallel Group Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics of Isavuconazole
This is a 2-part, open-label study, designed to evaluate the effect of renal disease on the pharmacokinetics of BAL4815 (active isavuconazole moiety) relative to the pharmacokinetics in healthy subjects with normal renal function.
Read the detailed description
In Part 1, eligible subjects will be enrolled into one of 2 groups based on their renal function. All subjects will receive a single 1-hour infusion of isavuconazole and will remain confined for 4 days. Subjects with normal renal function will return to the clinic for several outpatient visits over 15 days after dosing. Subjects with renal disease will complete the same outpatient visits which correspond to scheduled dialysis dates and then be readmitted to the clinic on study Day 15 to receive a second 1-hour infusion of isavuconazole followed by their normal dialysis procedure and then remain confined for 4 days. ECGs, vital signs, blood draws will be obtained throughout the study for safety and to assess the amount of study drug in the body as well as study drug removed in subjects undergoing dialysis.
In Part 2, eligible subjects will be enrolled into one of 4 groups based on their renal function. All subjects will receive a single 1-hour infusion of isavuconazole and remain confined for 4 days. Subjects will return to the clinic for several outpatient visits over 15 days after dosing. ECGs, vital signs, blood draws will be obtained throughout the study for safety and to assess the amount of study drug in the body.
- Being tested
- isavuconazole
- Keywords
- isavuconazole, BAL4815, BAL8557, BAL8728
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isavuconazoleDrug
Also called BAL4815, BAL8557
IV
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Subjects with End Stage Renal Disease (ESRD) | Experimental | Not described Receives: Drug: isavuconazole |
| Part 1 Healthy Subjects | Experimental | Not described Receives: Drug: isavuconazole |
| Part 2 Subjects with Mild Renal Impairment | Experimental | Not described Receives: Drug: isavuconazole |
| Part 2 Subjects with Moderate Renal Impairment | Experimental | Not described Receives: Drug: isavuconazole |
| Part 2 Subjects with Severe Renal Impairment | Experimental | Not described Receives: Drug: isavuconazole |
| Part 2 Subjects with no Renal Impairment | Experimental | Not described Receives: Drug: isavuconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics variables for BAL4815 (in plasma): AUC72 and Cmax
Area under the concentration-time curve from 0 to 72 hours (AUC72) and Maximum concentration (Cmax)
Measured: Day 1, Part 1
Pharmacokinetics variables for BAL4815 (in plasma): AUCinf, AUClast, and Cmax
Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf), Area under the plasma concentration-time curve from time of dosing to the last quantifiable concentration (AUClast)
Measured: Day 1, Part 2
Secondary outcomes (7)
Pharmacokinetics variables for BAL4815 (in plasma): AUCinf and AUClast
Measured: Day 1, Part 1
Pharmacokinetics variables for BAL4815 (in plasma): tmax, t1/2, Vz, and CLtot , Ae, Ae% , CLR
Time to attain maximum concentration (tmax), Apparent terminal elimination half-life (t ½), Apparent volume of distribution during terminal phase (Vz), Total clearance (CLtot), Cumulative amount of unchanged drug excreted in urine (Ae), Percent of drug excreted in urine (Ae%), Renal clearance of the drug from plasma (CLR)
Measured: Day 1, Parts 1 and 2
Pharmacokinetics unbound (u) variables for BAL4815 (in plasma and in urine): AUC inf,u, AUC72,u, AUClast,u, Cmax,u, Vz,u, CLtot,u, CLR,u
Measured: Day 1, Parts 1 and 2
Pharmacokinetics variables for End Stage Renal Disease (ESRD) subjects for BAL4815: AUC72, Cmax, and tmax
Measured: Day 15, Part 1
Pharmacokinetics variables for BAL8728 (in plasma and urine): AUCinf, AUClast, AUC72, Cmax, tmax , t1/2, Vz, CLtot, Ae, Ae% , CLR
Measured: Day 1, Parts 1 and 2
Pharmacokinetics variables for End Stage Renal Disease (ESRD) subjects for BAL8728: AUC72, Cmax, and tmax
Measured: Day 15, Part 1
Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs)
Measured: Part 1: Continuous, up to Day 24; Part 2: Continuous, up to Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics of 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01555866
- Sponsor's protocol ID
- 9766-CL-0018
- Status last verified
- Aug 2015
- First submitted
- 14 Mar 2012
- Last updated
- 1 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open Label, 2 Part, Parallel Group Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics of Isavuconazole
- ClinicalTrials.gov ID
- NCT01555866
- Acronym / sponsor ID
- 9766-CL-0018
- Keywords
- isavuconazole, BAL4815, BAL8557, BAL8728
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Study start
- Mar 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 16 Mar 2012 (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 2-part, open-label study, designed to evaluate the effect of renal disease on the pharmacokinetics of BAL4815 (active isavuconazole moiety) relative to the pharmacokinetics in healthy subjects with normal renal function.
Detailed description
In Part 1, eligible subjects will be enrolled into one of 2 groups based on their renal function. All subjects will receive a single 1-hour infusion of isavuconazole and will remain confined for 4 days. Subjects with normal renal function will return to the clinic for several outpatient visits over 15 days after dosing. Subjects with renal disease will complete the same outpatient visits which correspond to scheduled dialysis dates and then be readmitted to the clinic on study Day 15 to receive a second 1-hour infusion of isavuconazole followed by their normal dialysis procedure and then remain confined for 4 days. ECGs, vital signs, blood draws will be obtained throughout the study for safety and to assess the amount of study drug in the body as well as study drug removed in subjects undergoing dialysis.
In Part 2, eligible subjects will be enrolled into one of 4 groups based on their renal function. All subjects will receive a single 1-hour infusion of isavuconazole and remain confined for 4 days. Subjects will return to the clinic for several outpatient visits over 15 days after dosing. ECGs, vital signs, blood draws will be obtained throughout the study for safety and to assess the amount of study drug in the body.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1 Subjects with End Stage Renal Disease (ESRD) | Experimental | Drug: isavuconazole |
| Part 1 Healthy Subjects | Experimental | Drug: isavuconazole |
| Part 2 Subjects with Mild Renal Impairment | Experimental | Drug: isavuconazole |
| Part 2 Subjects with Moderate Renal Impairment | Experimental | Drug: isavuconazole |
| Part 2 Subjects with Severe Renal Impairment | Experimental | Drug: isavuconazole |
| Part 2 Subjects with no Renal Impairment | Experimental | Drug: isavuconazole |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject must weigh at least 45 kg and have a body mass index of 18-35 kg/m2
- If female, the subject agrees to sexual abstinence, is surgically sterile, postmenopausal or using a medically acceptable double-barrier method to prevent pregnancy and agrees to continue using this method during the study and until 28 days after final study dug administration. Female subjects must not be lactating or pregnant as documented by a negative pregnancy test at Screening and Day -1
- If male, the subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method during the study and until 90 days after the end of the study
- The subject has good venous access
- Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after final study drug administration.
Key exclusion criteria (17 listed)
- The subject has a previous history of any clinically significant gastro-intestinal, neurological, hepatic, pulmonary, metabolic, dermatologic, immunologic, cardiovascular, psychiatric, genitourinary, endocrine, hematological disorder or disease, malignancy excluding non-melanoma skin cancer or any other medical condition that would preclude participation in the study
- The subject has evidence of any cardiac conduction abnormalities
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia, torsade de pointes, structural heart disease, or family history of Long QT syndrome
- The subject has a supine systolic blood pressure less than 90 or greater than 160 mmHg, and diastolic blood pressure less than 50 or greater than 90 mmHg, or pulse rate less than 40 or greater than 100 beats per minute, either at Screening and Day -1
- The subject has a history of consuming more than 14 units of alcoholic beverages per week, has a history of alcohol abuse within the past 2 years prior to Screening, or has a positive screen for alcohol at Screening or Day -1. (NOTE: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor.)
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 |
|---|---|---|
| isavuconazoleAlso: BAL4815, BAL8557IV | Drug | Part 1 Healthy Subjects, Part 1 Subjects with End Stage Renal Disease (ESRD), Part 2 Subjects with Mild Renal Impairment, Part 2 Subjects with Moderate Renal Impairment, Part 2 Subjects with Severe Renal Impairment, Part 2 Subjects with no Renal Impairment |
Primary outcome
Pharmacokinetics variables for BAL4815 (in plasma): AUC72 and Cmax
Time frame: Day 1, Part 1
Area under the concentration-time curve from 0 to 72 hours (AUC72) and Maximum concentration (Cmax)
Pharmacokinetics variables for BAL4815 (in plasma): AUCinf, AUClast, and Cmax
Time frame: Day 1, Part 2
Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf), Area under the plasma concentration-time curve from time of dosing to the last quantifiable concentration (AUClast)
7 secondary outcomes
Pharmacokinetics variables for BAL4815 (in plasma): AUCinf and AUClast
Time frame: Day 1, Part 1
Pharmacokinetics variables for BAL4815 (in plasma): tmax, t1/2, Vz, and CLtot , Ae, Ae% , CLR
Time frame: Day 1, Parts 1 and 2
Pharmacokinetics unbound (u) variables for BAL4815 (in plasma and in urine): AUC inf,u, AUC72,u, AUClast,u, Cmax,u, Vz,u, CLtot,u, CLR,u
Time frame: Day 1, Parts 1 and 2
Pharmacokinetics variables for End Stage Renal Disease (ESRD) subjects for BAL4815: AUC72, Cmax, and tmax
Time frame: Day 15, Part 1
Pharmacokinetics variables for BAL8728 (in plasma and urine): AUCinf, AUClast, AUC72, Cmax, tmax , t1/2, Vz, CLtot, Ae, Ae% , CLR
Time frame: Day 1, Parts 1 and 2
Pharmacokinetics variables for End Stage Renal Disease (ESRD) subjects for BAL8728: AUC72, Cmax, and tmax
Time frame: Day 15, Part 1
Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs)
Time frame: Part 1: Continuous, up to Day 24; Part 2: Continuous, up to Day 15
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 1 Sep 2015.
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
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing isavuconazole in people with Pharmacokinetics of Isavuconazole and Healthy Volunteers, run by Astellas Pharma Global Development, Inc. at 3 sites 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 17 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 1 Sep 2015. 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 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?
Pharmacokinetics variables for BAL4815 (in plasma): AUC72 and Cmax (time frame: Day 1, Part 1). The study lists 2 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 1 Sep 2015.