Pharmacokinetics of IsavuconazolePhase 1NCT01657825
Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects
A Phase 1 study testing Isavuconazole and Warfarin in people with Pharmacokinetics of Isavuconazole and Pharmacokinetics of S- and R-warfarin, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of warfarin after single dose administration. 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 Isavuconazole, Pharmacokinetics of S- and R-warfarin, Pharmacodynamics of Warfarin
- What is being tested?
- Isavuconazole and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Jul 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
- Subjects must have BMI of 18 to 32 kg/m2 and a body weight of at least 45 kg
- Subjects must have normal laboratory values especially for ALT, AST, protein C and S, and prothrombin time
Who cannot join
- 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 (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
- The subject has a positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
- The subject has a known or suspected allergy to any of the components of the trial products or 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 is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1
- The subject has received an experimental agent within 30 days or 5 half-lives, whichever is longer prior to Day -1
- The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Warfarin in Healthy Male Subjects
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of warfarin after single dose administration.
Read the detailed description
Subjects will receive a single dose of warfarin on Day 1 followed by a 15 day wash-out period (time from warfarin dosing to isavuconazole dosing).
On Days 16 and 17, isavuconazole will be dosed three times daily (TID). TID doses will be administered 8 hours apart. On Days 18 through 28, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of warfarin on Day 20. A follow up visit will occur approximately 7 days after the last dose of isavuconazole. Blood samples for pharmacokinetics will be collected throughout the study.
- Conditions
- Pharmacokinetics of Isavuconazole, Pharmacokinetics of S- and R-warfarin, Pharmacodynamics of Warfarin, Healthy Volunteers
- Being tested
- Isavuconazole, Warfarin
- Keywords
- isavuconazole, warfarin, Healthy Volunteers, BAL8557, Coumadin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsavuconazoleDrug
Also called BAL8557
oral
WarfarinDrug
Also called Coumadin
oral
| Study group | Role | What they receive |
|---|---|---|
| Isavuconazole and warfarin | Experimental | Isavuconazole three times daily (TID) for 2 days followed by once daily (QD) dosing for 11 days and warfarin single doses on Days 1 and 20 Receives: Drug: Isavuconazole; Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax
Area under the curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to last quantifiable concentration (AUClast ), and maximum concentration (Cmax)
Measured: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
Secondary outcomes (6)
Composite of PK variables for R-warfarin (in plasma): AUCinf, AUClast, Cmax
Measured: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and t1/2
Time to attain Cmax (tmax) , apparent volume of distribution (Vz /F), apparent body clearance after oral dosing (CL/F), and apparent terminal elimination half-life (t1/2)
Measured: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
PK variable for isavuconazole (in plasma): trough concentration (Ctrough)
Measured: Days 18-20 and Days 22-27, predose and Day 28 predose and 24 hours post dose
Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax
AUC during the time interval between consecutive dosing (AUCtau)
Measured: Day 19 predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 16 hours post dose; and Day 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 36 hours postdose
Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT
International Normalized Ratio (INR), Maximum observed change INR value (MAXINR), Area under the INR time curve from 0 to 216 hours (AUCINR), Maximum observed change in prothrombin time (PT)value (MAXPT), Area under the PT time curve from 0 to 216 hours (AUCPT)
Measured: Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs
Measured: Day 1 through Day 29, Day 35 ± 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2012 (estimated)
- Study startJun 2012
- Primary completionJul 2012
- Study completionJul 2012
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT01657825
- Sponsor's protocol ID
- 9766-CL-0033
- Status last verified
- Aug 2012
- First submitted
- 2 Aug 2012
- Last updated
- 28 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Warfarin in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT01657825
- Acronym / sponsor ID
- 9766-CL-0033
- Conditions
- Pharmacokinetics of Isavuconazole, Pharmacokinetics of S- and R-warfarin, Pharmacodynamics of Warfarin, Healthy Volunteers
- Keywords
- isavuconazole, warfarin, Healthy Volunteers, BAL8557, Coumadin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Study start
- Jun 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 6 Aug 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.
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of warfarin after single dose administration.
Detailed description
Subjects will receive a single dose of warfarin on Day 1 followed by a 15 day wash-out period (time from warfarin dosing to isavuconazole dosing).
On Days 16 and 17, isavuconazole will be dosed three times daily (TID). TID doses will be administered 8 hours apart. On Days 18 through 28, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of warfarin on Day 20. A follow up visit will occur approximately 7 days after the last dose of isavuconazole. Blood samples for pharmacokinetics will be collected throughout the study.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Isavuconazole and warfarin | Experimental | Drug: Isavuconazole, Drug: WarfarinIsavuconazole three times daily (TID) for 2 days followed by once daily (QD) dosing for 11 days and warfarin single doses on Days 1 and 20 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Subjects must have BMI of 18 to 32 kg/m2 and a body weight of at least 45 kg
- Subjects must have normal laboratory values especially for ALT, AST, protein C and S, and prothrombin time
Key exclusion criteria (7 listed)
- 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 (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
- The subject has a positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
- The subject has a known or suspected allergy to any of the components of the trial products or 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 is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1
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: BAL8557oral | Drug | Isavuconazole and warfarin |
| WarfarinAlso: Coumadinoral | Drug | Isavuconazole and warfarin |
Primary outcome
Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax
Time frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
Area under the curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to last quantifiable concentration (AUClast ), and maximum concentration (Cmax)
6 secondary outcomes
Composite of PK variables for R-warfarin (in plasma): AUCinf, AUClast, Cmax
Time frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
Composite of Pharmacokinetic (PK) variables for S-warfarin and R-warfarin (in plasma): tmax, Vz /F, CL/F, and t1/2
Time frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose
PK variable for isavuconazole (in plasma): trough concentration (Ctrough)
Time frame: Days 18-20 and Days 22-27, predose and Day 28 predose and 24 hours post dose
Composite of PK variable for isavuconazole (in plasma): AUCtau , Cmax, and tmax
Time frame: Day 19 predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 16 hours post dose; and Day 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 36 hours postdose
Pharmacodynamic Variables: MAXINR, AUCINR, MAXPT, and AUCPT
Time frame: Day 1 and Day 20 predose and at 6, 12, 24, 48, 72, 96, 168, and 216 hours post-warfarin-dose
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs
Time frame: Day 1 through Day 29, Day 35 ± 2
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 28 Aug 2012.
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
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 Isavuconazole and Warfarin in people with Pharmacokinetics of Isavuconazole and Pharmacokinetics of S- and R-warfarin, 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 2 inclusion and 7 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 28 Aug 2012. 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?
Composite of Pharmacokinetic (PK) variables for S-warfarin (in plasma): AUCinf, AUClast, Cmax (time frame: Days 1 and 20, predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12,16, 24, 48, 72, 96, 120, 144, 168, and 216 hours postdose). 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 28 Aug 2012.